---
_id: '7207'
abstract:
- lang: eng
text: The hippocampus plays key roles in learning and memory and is a main target
of Alzheimer's disease (AD), which causes progressive memory impairments. Despite
numerous investigations about the processes required for the normal hippocampal
functions, the neurotransmitter receptors involved in the synaptic deficits by
which AD disables the hippocampus are not yet characterized. By combining histoblots,
western blots, immunohistochemistry and high‐resolution immunoelectron microscopic
methods for GABAB receptors, this study provides a quantitative description of
the expression and the subcellular localization of GABAB1 in the hippocampus in
a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots
showed that the total amount of protein and the laminar expression pattern of
GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast,
immunoelectron microscopic techniques showed that the subcellular localization
of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age,
was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal
cells at 6 months of age and significantly reduced at the membrane surface of
CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1
was paralleled by a significant increase of the subunit at the intracellular sites.
We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals
contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent
reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the
hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated
synaptic transmission taking place in AD.
article_processing_charge: No
article_type: original
author:
- first_name: Alejandro
full_name: Martín-Belmonte, Alejandro
last_name: Martín-Belmonte
- first_name: Carolina
full_name: Aguado, Carolina
last_name: Aguado
- first_name: Rocío
full_name: Alfaro-Ruíz, Rocío
last_name: Alfaro-Ruíz
- first_name: Ana Esther
full_name: Moreno-Martínez, Ana Esther
last_name: Moreno-Martínez
- first_name: Luis
full_name: De La Ossa, Luis
last_name: De La Ossa
- first_name: José
full_name: Martínez-Hernández, José
last_name: Martínez-Hernández
- first_name: Alain
full_name: Buisson, Alain
last_name: Buisson
- first_name: Simon
full_name: Früh, Simon
last_name: Früh
- first_name: Bernhard
full_name: Bettler, Bernhard
last_name: Bettler
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Rafael
full_name: Luján, Rafael
last_name: Luján
citation:
ama: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Reduction in the neuronal
surface of post and presynaptic GABA>B< receptors in the hippocampus in
a mouse model of Alzheimer’s disease. Brain Pathology. 2020;30(3):554-575.
doi:10.1111/bpa.12802
apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De
La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Reduction in the neuronal
surface of post and presynaptic GABA>B< receptors in the hippocampus in
a mouse model of Alzheimer’s disease. Brain Pathology. Wiley. https://doi.org/10.1111/bpa.12802
chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther
Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, et al.
“Reduction in the Neuronal Surface of Post and Presynaptic GABA>B< Receptors
in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” Brain Pathology.
Wiley, 2020. https://doi.org/10.1111/bpa.12802.
ieee: A. Martín-Belmonte et al., “Reduction in the neuronal surface of post
and presynaptic GABA>B< receptors in the hippocampus in a mouse model
of Alzheimer’s disease,” Brain Pathology, vol. 30, no. 3. Wiley, pp. 554–575,
2020.
ista: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa
L, Martínez-Hernández J, Buisson A, Früh S, Bettler B, Shigemoto R, Fukazawa Y,
Luján R. 2020. Reduction in the neuronal surface of post and presynaptic GABA>B<
receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology.
30(3), 554–575.
mla: Martín-Belmonte, Alejandro, et al. “Reduction in the Neuronal Surface of Post
and Presynaptic GABA>B< Receptors in the Hippocampus in a Mouse Model
of Alzheimer’s Disease.” Brain Pathology, vol. 30, no. 3, Wiley, 2020,
pp. 554–75, doi:10.1111/bpa.12802.
short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De
La Ossa, J. Martínez-Hernández, A. Buisson, S. Früh, B. Bettler, R. Shigemoto,
Y. Fukazawa, R. Luján, Brain Pathology 30 (2020) 554–575.
date_created: 2019-12-22T23:00:43Z
date_published: 2020-05-01T00:00:00Z
date_updated: 2025-07-10T11:54:22Z
day: '01'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1111/bpa.12802
ec_funded: 1
external_id:
isi:
- '000502270900001'
pmid:
- '31729777'
file:
- access_level: open_access
checksum: 549cc1b18f638a21d17a939ba5563fa9
content_type: application/pdf
creator: dernst
date_created: 2020-09-22T09:47:19Z
date_updated: 2020-09-22T09:47:19Z
file_id: '8554'
file_name: 2020_BrainPathology_MartinBelmonte.pdf
file_size: 4220935
relation: main_file
success: 1
file_date_updated: 2020-09-22T09:47:19Z
has_accepted_license: '1'
intvolume: ' 30'
isi: 1
issue: '3'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 554-575
pmid: 1
project:
- _id: 25CBA828-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '720270'
name: Human Brain Project Specific Grant Agreement 1
- _id: 26436750-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '785907'
name: Human Brain Project Specific Grant Agreement 2
publication: Brain Pathology
publication_identifier:
eissn:
- 1750-3639
issn:
- 1015-6305
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Reduction in the neuronal surface of post and presynaptic GABA>B< receptors
in the hippocampus in a mouse model of Alzheimer's disease
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 30
year: '2020'
...
---
_id: '7339'
abstract:
- lang: eng
text: Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin)
dynamically support cell structure and functions. In central presynaptic terminals,
F-actin is expressed along the release edge and reportedly plays diverse functional
roles, but whether axonal MTs extend deep into terminals and play any physiological
role remains controversial. At the calyx of Held in rats of either sex, confocal
and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal
swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological
analysis demonstrated that depolymerization of MTs specifically prolonged the
slow-recovery time component of EPSCs from short-term depression induced by a
train of high-frequency stimulation, whereas depolymerization of F-actin specifically
prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic
action potential recordings, depolymerization of MTs or F-actin significantly
impaired the fidelity of high-frequency neurotransmission. We conclude that MTs
and F-actin differentially contribute to slow and fast SV replenishment, thereby
maintaining high-frequency neurotransmission.
article_processing_charge: No
article_type: original
author:
- first_name: Lashmi
full_name: Piriya Ananda Babu, Lashmi
last_name: Piriya Ananda Babu
- first_name: Han Ying
full_name: Wang, Han Ying
last_name: Wang
- first_name: Kohgaku
full_name: Eguchi, Kohgaku
id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
last_name: Eguchi
orcid: 0000-0002-6170-2546
- first_name: Laurent
full_name: Guillaud, Laurent
last_name: Guillaud
- first_name: Tomoyuki
full_name: Takahashi, Tomoyuki
last_name: Takahashi
citation:
ama: Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. Microtubule
and actin differentially regulate synaptic vesicle cycling to maintain high-frequency
neurotransmission. Journal of neuroscience. 2020;40(1):131-142. doi:10.1523/JNEUROSCI.1571-19.2019
apa: Piriya Ananda Babu, L., Wang, H. Y., Eguchi, K., Guillaud, L., & Takahashi,
T. (2020). Microtubule and actin differentially regulate synaptic vesicle cycling
to maintain high-frequency neurotransmission. Journal of Neuroscience.
Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1571-19.2019
chicago: Piriya Ananda Babu, Lashmi, Han Ying Wang, Kohgaku Eguchi, Laurent Guillaud,
and Tomoyuki Takahashi. “Microtubule and Actin Differentially Regulate Synaptic
Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal of Neuroscience.
Society for Neuroscience, 2020. https://doi.org/10.1523/JNEUROSCI.1571-19.2019.
ieee: L. Piriya Ananda Babu, H. Y. Wang, K. Eguchi, L. Guillaud, and T. Takahashi,
“Microtubule and actin differentially regulate synaptic vesicle cycling to maintain
high-frequency neurotransmission,” Journal of neuroscience, vol. 40, no.
1. Society for Neuroscience, pp. 131–142, 2020.
ista: Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. 2020. Microtubule
and actin differentially regulate synaptic vesicle cycling to maintain high-frequency
neurotransmission. Journal of neuroscience. 40(1), 131–142.
mla: Piriya Ananda Babu, Lashmi, et al. “Microtubule and Actin Differentially Regulate
Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal
of Neuroscience, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 131–42,
doi:10.1523/JNEUROSCI.1571-19.2019.
short: L. Piriya Ananda Babu, H.Y. Wang, K. Eguchi, L. Guillaud, T. Takahashi, Journal
of Neuroscience 40 (2020) 131–142.
date_created: 2020-01-19T23:00:38Z
date_published: 2020-01-02T00:00:00Z
date_updated: 2026-04-16T08:27:29Z
day: '02'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.1571-19.2019
external_id:
isi:
- '000505167600013'
pmid:
- '31767677'
file:
- access_level: open_access
checksum: 92f5e8a47f454fc131fb94cd7f106e60
content_type: application/pdf
creator: dernst
date_created: 2020-01-20T14:44:10Z
date_updated: 2020-07-14T12:47:56Z
file_id: '7345'
file_name: 2020_JourNeuroscience_Piriya.pdf
file_size: 4460781
relation: main_file
file_date_updated: 2020-07-14T12:47:56Z
has_accepted_license: '1'
intvolume: ' 40'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 131-142
pmid: 1
publication: Journal of neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microtubule and actin differentially regulate synaptic vesicle cycling to maintain
high-frequency neurotransmission
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 40
year: '2020'
...
---
_id: '8532'
abstract:
- lang: eng
text: The molecular anatomy of synapses defines their characteristics in transmission
and plasticity. Precise measurements of the number and distribution of synaptic
proteins are important for our understanding of synapse heterogeneity within and
between brain regions. Freeze–fracture replica immunogold electron microscopy
enables us to analyze them quantitatively on a two-dimensional membrane surface.
Here, we introduce Darea software, which utilizes deep learning for analysis of
replica images and demonstrate its usefulness for quick measurements of the pre-
and postsynaptic areas, density and distribution of gold particles at synapses
in a reproducible manner. We used Darea for comparing glutamate receptor and calcium
channel distributions between hippocampal CA3-CA1 spine synapses on apical and
basal dendrites, which differ in signaling pathways involved in synaptic plasticity.
We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic
size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA)
receptors with size. Interestingly, AMPA and NMDA receptors are segregated within
postsynaptic sites and negatively correlated in density among both apical and
basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels
show similar densities in apical and basal synapses with distributions consistent
with an exclusion zone model of calcium channel-release site topography.
acknowledgement: "This research was funded by Austrian Academy of Sciences, DOC fellowship
to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human
Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner
for technical support."
article_number: '6737'
article_processing_charge: No
article_type: original
author:
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Jacqueline-Claire
full_name: Montanaro-Punzengruber, Jacqueline-Claire
id: 3786AB44-F248-11E8-B48F-1D18A9856A87
last_name: Montanaro-Punzengruber
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: Matthew J
full_name: Case, Matthew J
id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Case
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture
replica images applied to glutamate receptors and calcium channels at hippocampal
synapses. International Journal of Molecular Sciences. 2020;21(18). doi:10.3390/ijms21186737
apa: Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J.,
Fukazawa, Y., & Shigemoto, R. (2020). Deep learning-assisted high-throughput
analysis of freeze-fracture replica images applied to glutamate receptors and
calcium channels at hippocampal synapses. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms21186737
chicago: Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari,
Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted
High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate
Receptors and Calcium Channels at Hippocampal Synapses.” International Journal
of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21186737.
ieee: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y.
Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of
freeze-fracture replica images applied to glutamate receptors and calcium channels
at hippocampal synapses,” International Journal of Molecular Sciences,
vol. 21, no. 18. MDPI, 2020.
ista: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture
replica images applied to glutamate receptors and calcium channels at hippocampal
synapses. International Journal of Molecular Sciences. 21(18), 6737.
mla: Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis
of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels
at Hippocampal Synapses.” International Journal of Molecular Sciences,
vol. 21, no. 18, 6737, MDPI, 2020, doi:10.3390/ijms21186737.
short: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y.
Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).
corr_author: '1'
date_created: 2020-09-20T22:01:35Z
date_published: 2020-09-14T00:00:00Z
date_updated: 2026-06-29T22:31:06Z
day: '14'
ddc:
- '570'
department:
- _id: RySh
doi: 10.3390/ijms21186737
ec_funded: 1
external_id:
isi:
- '000579945300001'
file:
- access_level: open_access
checksum: 2e4f62f3cfe945b7391fc3070e5a289f
content_type: application/pdf
creator: dernst
date_created: 2020-09-21T14:08:58Z
date_updated: 2020-09-21T14:08:58Z
file_id: '8551'
file_name: 2020_JournMolecSciences_Kleindienst.pdf
file_size: 5748456
relation: main_file
success: 1
file_date_updated: 2020-09-21T14:08:58Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '18'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 25D32BC0-B435-11E9-9278-68D0E5697425
name: Mechanism of formation and maintenance of input side-dependent asymmetry in
the hippocampus
- _id: 26436750-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '785907'
name: Human Brain Project Specific Grant Agreement 2
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- 1422-0067
issn:
- 1661-6596
publication_status: published
publisher: MDPI
quality_controlled: '1'
related_material:
record:
- id: '9562'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Deep learning-assisted high-throughput analysis of freeze-fracture replica
images applied to glutamate receptors and calcium channels at hippocampal synapses
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 21
year: '2020'
...
---
OA_place: publisher
_id: '7525'
abstract:
- lang: eng
text: "The medial habenula (MHb) is an evolutionary conserved epithalamic structure
important for the modulation of emotional memory. It is involved in regulation
of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and
feeding behavior. MHb receives inputs from septal regions and projects exclusively
to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project
to different subnuclei of MHb: the bed nucleus of anterior commissure projects
to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore,
the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively.
Importantly, these projections have unique features of prominent co-release of
different neurotransmitters and requirement of a peculiar type of calcium channel
for release. In general, synaptic neurotransmission requires an activity-dependent
influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels.
The calcium channel family most commonly involved in neurotransmitter release
comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits,
respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or
Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of
the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements.
This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique
mechanisms of glutamate release in this pathway. One potential example of such
uniqueness is the facilitation of release by GABAB receptor (GBR) activation.
Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting
presynaptic calcium channels. MHb shows the highest expression levels of GBR in
the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are
associated with auxiliary subunits, called potassium channel tetramerization domain
containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b
is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression
in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b
may be involved in the unique mechanisms of neurotransmitter release mediated
by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we
first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways
is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482.
We next found that baclofen, a GBR agonist, has facilitatory effects on release
from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on
release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed
exclusively in ventral MHb may have a role in the facilitatory effects of GBR
activation. In a heterologous expression system using HEK cells, we found that
KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold
electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely
in presynaptic active zone in IPN with KCTD12b being present only in rostral/central
but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely
in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements
and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3,
KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating
that they may form complexes regulating vesicle release in rostral IPN. \r\nOn
electrophysiological studies of wild type (WT) mice, we found that paired-pulse
ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT
and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release
probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8
KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO
mice, the mean variance analysis revealed significantly lower release probability
in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional
regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation
in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8
and KCTD12b KO mice, and found the facilitation of release remained in both KO
mice, indicating that the peculiar effects of the GBR activation in this pathway
do not depend on the selective expression of these KCTD subunits in ventral MHb.
However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen
falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and
KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained
potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in
its termination in the absence of KCTD12b. Consistent with these functional findings,
replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or
GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT
mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the
release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn
summary, our study provided new insights into the physiological roles of presynaptic
Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal
circuit. Future studies will be required to identify the exact molecular mechanism
underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals.
It remains to be determined whether the prominent presence of presynaptic KCTDs
at active zone could exert similar neuromodulatory functions in different pathways
of the brain.\r\n"
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
citation:
ama: Bhandari P. Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525
apa: Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7525
chicago: Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology
Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525.
ieee: P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway,” Institute of Science and Technology Austria,
2020.
ista: Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria.
mla: Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology
Austria, 2020, doi:10.15479/AT:ISTA:7525.
short: P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula
to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria,
2020.
corr_author: '1'
date_created: 2020-02-26T10:56:37Z
date_published: 2020-02-28T00:00:00Z
date_updated: 2026-04-08T07:27:27Z
day: '28'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:7525
file:
- access_level: open_access
checksum: 4589234fdb12b4ad72273b311723a7b4
content_type: application/pdf
creator: pbhandari
date_created: 2020-02-28T08:37:53Z
date_updated: 2021-03-01T23:30:04Z
embargo: 2021-02-28
file_id: '7538'
file_name: Pradeep Bhandari Thesis.pdf
file_size: 9646346
relation: main_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
- access_level: closed
checksum: aa79490553ca0a5c9b6fbcd152e93928
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: pbhandari
date_created: 2020-02-28T08:47:14Z
date_updated: 2021-03-01T23:30:04Z
embargo_to: open_access
file_id: '7539'
file_name: Pradeep Bhandari Thesis.docx
file_size: 35252164
relation: source_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
file_date_updated: 2021-03-01T23:30:04Z
has_accepted_license: '1'
keyword:
- Cav2.3
- medial habenula (MHb)
- interpeduncular nucleus (IPN)
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '79'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
OA_type: free access
_id: '6659'
abstract:
- lang: eng
text: Chemical labeling of proteins with synthetic molecular probes offers the possibility
to probe the functions of proteins of interest in living cells. However, the methods
for covalently labeling targeted proteins using complementary peptide tag-probe
pairs are still limited, irrespective of the versatility of such pairs in biological
research. Herein, we report the new CysHis tag-Ni(II) probe pair for the specific
covalent labeling of proteins. A broad-range evaluation of the reactivity profiles
of the probe and the CysHis peptide tag afforded a tag-probe pair with an optimized
and high labeling selectivity and reactivity. In particular, the labeling specificity
of this pair was notably improved compared to the previously reported one. This
pair was successfully utilized for the fluorescence imaging of membrane proteins
on the surfaces of living cells, demonstrating its potential utility in biological
research.
acknowledgement: his work was supported by the Grant-in-Aid for Scientific Research
B (JSPS KAKENHI grant no. JP17H03090 to A. O.); the Scientific Research on Innovative
Areas “Chemistry for Multimolecular Crowding Biosystems” (JSPS KAKENHI grant no.
JP17H06349 to A. O.); and the European Union (European Research Council Advanced
grant no. 694539 and Human Brain Project Ref. 720270 to R. S.). A. O. acknowledges
the financial support of the Takeda Science Foundation.
article_processing_charge: No
article_type: original
author:
- first_name: Naoki
full_name: Zenmyo, Naoki
last_name: Zenmyo
- first_name: Hiroki
full_name: Tokumaru, Hiroki
last_name: Tokumaru
- first_name: Shohei
full_name: Uchinomiya, Shohei
last_name: Uchinomiya
- first_name: Hirokazu
full_name: Fuchida, Hirokazu
last_name: Fuchida
- first_name: Shigekazu
full_name: Tabata, Shigekazu
id: 4427179E-F248-11E8-B48F-1D18A9856A87
last_name: Tabata
- first_name: Itaru
full_name: Hamachi, Itaru
last_name: Hamachi
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Akio
full_name: Ojida, Akio
last_name: Ojida
citation:
ama: Zenmyo N, Tokumaru H, Uchinomiya S, et al. Optimized reaction pair of the CysHis
tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins.
Bulletin of the Chemical Society of Japan. 2019;92(5):995-1000. doi:10.1246/bcsj.20190034
apa: Zenmyo, N., Tokumaru, H., Uchinomiya, S., Fuchida, H., Tabata, S., Hamachi,
I., … Ojida, A. (2019). Optimized reaction pair of the CysHis tag and Ni(II)-NTA
probe for highly selective chemical labeling of membrane proteins. Bulletin
of the Chemical Society of Japan. Bulletin of the Chemical Society of Japan.
https://doi.org/10.1246/bcsj.20190034
chicago: Zenmyo, Naoki, Hiroki Tokumaru, Shohei Uchinomiya, Hirokazu Fuchida, Shigekazu
Tabata, Itaru Hamachi, Ryuichi Shigemoto, and Akio Ojida. “Optimized Reaction
Pair of the CysHis Tag and Ni(II)-NTA Probe for Highly Selective Chemical Labeling
of Membrane Proteins.” Bulletin of the Chemical Society of Japan. Bulletin
of the Chemical Society of Japan, 2019. https://doi.org/10.1246/bcsj.20190034.
ieee: N. Zenmyo et al., “Optimized reaction pair of the CysHis tag and Ni(II)-NTA
probe for highly selective chemical labeling of membrane proteins,” Bulletin
of the Chemical Society of Japan, vol. 92, no. 5. Bulletin of the Chemical
Society of Japan, pp. 995–1000, 2019.
ista: Zenmyo N, Tokumaru H, Uchinomiya S, Fuchida H, Tabata S, Hamachi I, Shigemoto
R, Ojida A. 2019. Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe
for highly selective chemical labeling of membrane proteins. Bulletin of the Chemical
Society of Japan. 92(5), 995–1000.
mla: Zenmyo, Naoki, et al. “Optimized Reaction Pair of the CysHis Tag and Ni(II)-NTA
Probe for Highly Selective Chemical Labeling of Membrane Proteins.” Bulletin
of the Chemical Society of Japan, vol. 92, no. 5, Bulletin of the Chemical
Society of Japan, 2019, pp. 995–1000, doi:10.1246/bcsj.20190034.
short: N. Zenmyo, H. Tokumaru, S. Uchinomiya, H. Fuchida, S. Tabata, I. Hamachi,
R. Shigemoto, A. Ojida, Bulletin of the Chemical Society of Japan 92 (2019) 995–1000.
date_created: 2019-07-21T21:59:16Z
date_published: 2019-05-15T00:00:00Z
date_updated: 2025-09-10T10:37:21Z
day: '15'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1246/bcsj.20190034
ec_funded: 1
external_id:
isi:
- '000468101800007'
has_accepted_license: '1'
intvolume: ' 92'
isi: 1
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1246/bcsj.20190034
month: '05'
oa: 1
oa_version: Published Version
page: 995-1000
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
publication: Bulletin of the Chemical Society of Japan
publication_identifier:
issn:
- 0009-2673
publication_status: published
publisher: Bulletin of the Chemical Society of Japan
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective
chemical labeling of membrane proteins
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 92
year: '2019'
...
---
_id: '6868'
abstract:
- lang: eng
text: "Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control
electrical rhythmicity and excitability in the heart and brain, but the function
of HCN channels at the subcellular level in axons remains poorly understood. Here,
we show that the action potential conduction velocity in both myelinated and unmyelinated
central axons can be bidirectionally modulated by a HCN channel blocker, cyclic
adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar
mossy fiber boutons show that HCN channels ensure reliable high-frequency firing
and are strongly modulated by cAMP (EC50 40 mM; estimated endogenous cAMP concentration
13 mM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating
subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2
channels control conduction velocity primarily by altering the resting membrane
potential\r\nand are associated with significant metabolic costs. These results
suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity
to finely tune energy consumption and temporal delays across axons in the brain."
article_number: e42766
article_processing_charge: No
article_type: original
author:
- first_name: Niklas
full_name: Byczkowicz, Niklas
last_name: Byczkowicz
- first_name: Abdelmoneim
full_name: Eshra, Abdelmoneim
last_name: Eshra
- first_name: Jacqueline-Claire
full_name: Montanaro-Punzengruber, Jacqueline-Claire
id: 3786AB44-F248-11E8-B48F-1D18A9856A87
last_name: Montanaro-Punzengruber
- first_name: Andrea
full_name: Trevisiol, Andrea
last_name: Trevisiol
- first_name: Johannes
full_name: Hirrlinger, Johannes
last_name: Hirrlinger
- first_name: Maarten Hp
full_name: Kole, Maarten Hp
last_name: Kole
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Stefan
full_name: Hallermann, Stefan
last_name: Hallermann
citation:
ama: Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, et al. HCN channel-mediated
neuromodulation can control action potential velocity and fidelity in central
axons. eLife. 2019;8. doi:10.7554/eLife.42766
apa: Byczkowicz, N., Eshra, A., Montanaro-Punzengruber, J.-C., Trevisiol, A., Hirrlinger,
J., Kole, M. H., … Hallermann, S. (2019). HCN channel-mediated neuromodulation
can control action potential velocity and fidelity in central axons. ELife.
eLife Sciences Publications. https://doi.org/10.7554/eLife.42766
chicago: Byczkowicz, Niklas, Abdelmoneim Eshra, Jacqueline-Claire Montanaro-Punzengruber,
Andrea Trevisiol, Johannes Hirrlinger, Maarten Hp Kole, Ryuichi Shigemoto, and
Stefan Hallermann. “HCN Channel-Mediated Neuromodulation Can Control Action Potential
Velocity and Fidelity in Central Axons.” ELife. eLife Sciences Publications,
2019. https://doi.org/10.7554/eLife.42766.
ieee: N. Byczkowicz et al., “HCN channel-mediated neuromodulation can control
action potential velocity and fidelity in central axons,” eLife, vol. 8.
eLife Sciences Publications, 2019.
ista: Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, Trevisiol A, Hirrlinger
J, Kole MH, Shigemoto R, Hallermann S. 2019. HCN channel-mediated neuromodulation
can control action potential velocity and fidelity in central axons. eLife. 8,
e42766.
mla: Byczkowicz, Niklas, et al. “HCN Channel-Mediated Neuromodulation Can Control
Action Potential Velocity and Fidelity in Central Axons.” ELife, vol. 8,
e42766, eLife Sciences Publications, 2019, doi:10.7554/eLife.42766.
short: N. Byczkowicz, A. Eshra, J.-C. Montanaro-Punzengruber, A. Trevisiol, J. Hirrlinger,
M.H. Kole, R. Shigemoto, S. Hallermann, ELife 8 (2019).
date_created: 2019-09-15T22:00:43Z
date_published: 2019-09-09T00:00:00Z
date_updated: 2026-04-03T09:40:28Z
day: '09'
ddc:
- '570'
department:
- _id: RySh
doi: 10.7554/eLife.42766
external_id:
isi:
- '000485663900001'
file:
- access_level: open_access
checksum: c350b7861ef0fb537cae8a3232aec016
content_type: application/pdf
creator: dernst
date_created: 2019-09-16T13:14:33Z
date_updated: 2020-07-14T12:47:42Z
file_id: '6880'
file_name: 2019_eLife_Byczkowicz.pdf
file_size: 4008137
relation: main_file
file_date_updated: 2020-07-14T12:47:42Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: HCN channel-mediated neuromodulation can control action potential velocity
and fidelity in central axons
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 8
year: '2019'
...
---
_id: '7099'
acknowledgement: "The authors thank Gabi Schmid for excellent technical support. We
also thank\r\nDr. H. Harada, Dr. W. Kaufmann, and Dr. B. Kapelari for testing the
specificity\r\nof some of the antibodies used in this study on replicas. Funding
was provided\r\nby the Austrian Science Fund (Fonds zur Fo¨ rderung der Wissenschaftlichen\r\nForschung)
Sonderforschungsbereich grants F44-17 (to F.jF.), F44-10 and\r\nP25375-B24 (to N.S.),
and P26680 (to G.S.) and by the Novartis Research\r\nFoundation and the Swiss National
Science Foundation (to A.L). We also thank\r\nProf. M. Capogna for reading a previous
version of the manuscript."
article_processing_charge: No
article_type: original
author:
- first_name: Yu
full_name: Kasugai, Yu
last_name: Kasugai
- first_name: Elisabeth
full_name: Vogel, Elisabeth
last_name: Vogel
- first_name: Heide
full_name: Hörtnagl, Heide
last_name: Hörtnagl
- first_name: Sabine
full_name: Schönherr, Sabine
last_name: Schönherr
- first_name: Enrica
full_name: Paradiso, Enrica
last_name: Paradiso
- first_name: Markus
full_name: Hauschild, Markus
last_name: Hauschild
- first_name: Georg
full_name: Göbel, Georg
last_name: Göbel
- first_name: Ivan
full_name: Milenkovic, Ivan
last_name: Milenkovic
- first_name: Yvan
full_name: Peterschmitt, Yvan
last_name: Peterschmitt
- first_name: Ramon
full_name: Tasan, Ramon
last_name: Tasan
- first_name: Günther
full_name: Sperk, Günther
last_name: Sperk
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Werner
full_name: Sieghart, Werner
last_name: Sieghart
- first_name: Nicolas
full_name: Singewald, Nicolas
last_name: Singewald
- first_name: Andreas
full_name: Lüthi, Andreas
last_name: Lüthi
- first_name: Francesco
full_name: Ferraguti, Francesco
last_name: Ferraguti
citation:
ama: Kasugai Y, Vogel E, Hörtnagl H, et al. Structural and functional remodeling
of amygdala GABAergic synapses in associative fear learning. Neuron. 2019;104(4):781-794.e4.
doi:10.1016/j.neuron.2019.08.013
apa: Kasugai, Y., Vogel, E., Hörtnagl, H., Schönherr, S., Paradiso, E., Hauschild,
M., … Ferraguti, F. (2019). Structural and functional remodeling of amygdala GABAergic
synapses in associative fear learning. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.08.013
chicago: Kasugai, Yu, Elisabeth Vogel, Heide Hörtnagl, Sabine Schönherr, Enrica
Paradiso, Markus Hauschild, Georg Göbel, et al. “Structural and Functional Remodeling
of Amygdala GABAergic Synapses in Associative Fear Learning.” Neuron. Elsevier,
2019. https://doi.org/10.1016/j.neuron.2019.08.013.
ieee: Y. Kasugai et al., “Structural and functional remodeling of amygdala
GABAergic synapses in associative fear learning,” Neuron, vol. 104, no.
4. Elsevier, p. 781–794.e4, 2019.
ista: Kasugai Y, Vogel E, Hörtnagl H, Schönherr S, Paradiso E, Hauschild M, Göbel
G, Milenkovic I, Peterschmitt Y, Tasan R, Sperk G, Shigemoto R, Sieghart W, Singewald
N, Lüthi A, Ferraguti F. 2019. Structural and functional remodeling of amygdala
GABAergic synapses in associative fear learning. Neuron. 104(4), 781–794.e4.
mla: Kasugai, Yu, et al. “Structural and Functional Remodeling of Amygdala GABAergic
Synapses in Associative Fear Learning.” Neuron, vol. 104, no. 4, Elsevier,
2019, p. 781–794.e4, doi:10.1016/j.neuron.2019.08.013.
short: Y. Kasugai, E. Vogel, H. Hörtnagl, S. Schönherr, E. Paradiso, M. Hauschild,
G. Göbel, I. Milenkovic, Y. Peterschmitt, R. Tasan, G. Sperk, R. Shigemoto, W.
Sieghart, N. Singewald, A. Lüthi, F. Ferraguti, Neuron 104 (2019) 781–794.e4.
date_created: 2019-11-25T08:02:39Z
date_published: 2019-11-20T00:00:00Z
date_updated: 2023-08-30T07:28:22Z
day: '20'
ddc:
- '571'
- '599'
department:
- _id: RySh
doi: 10.1016/j.neuron.2019.08.013
external_id:
isi:
- '000497963500017'
pmid:
- '31543297'
has_accepted_license: '1'
intvolume: ' 104'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.neuron.2019.08.013
month: '11'
oa: 1
oa_version: Published Version
page: 781-794.e4
pmid: 1
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Structural and functional remodeling of amygdala GABAergic synapses in associative
fear learning
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 104
year: '2019'
...
---
_id: '7179'
abstract:
- lang: eng
text: Glutamate is the major excitatory neurotransmitter in the CNS binding to a
variety of glutamate receptors. Metabotropic glutamate receptors (mGluR1 to mGluR8)
can act excitatory or inhibitory, depending on associated signal cascades. Expression
and localization of inhibitory acting mGluRs at inner hair cells (IHCs) in the
cochlea are largely unknown. Here, we analyzed expression of mGluR2, mGluR3, mGluR4,
mGluR6, mGluR7, and mGluR8 and investigated their localization with respect to
the presynaptic ribbon of IHC synapses. We detected transcripts for mGluR2, mGluR3,
and mGluR4 as well as for mGluR7a, mGluR7b, mGluR8a, and mGluR8b splice variants.
Using receptor-specific antibodies in cochlear wholemounts, we found expression
of mGluR2, mGluR4, and mGluR8b close to presynaptic ribbons. Super resolution
and confocal microscopy in combination with 3-dimensional reconstructions indicated
a postsynaptic localization of mGluR2 that overlaps with postsynaptic density
protein 95 on dendrites of afferent type I spiral ganglion neurons. In contrast,
mGluR4 and mGluR8b were expressed at the presynapse close to IHC ribbons. In summary,
we localized in detail 3 mGluR types at IHC ribbon synapses, providing a fundament
for new therapeutical strategies that could protect the cochlea against noxious
stimuli and excitotoxicity.
article_processing_charge: No
article_type: original
author:
- first_name: Lisa
full_name: Klotz, Lisa
last_name: Klotz
- first_name: Olaf
full_name: Wendler, Olaf
last_name: Wendler
- first_name: Renato
full_name: Frischknecht, Renato
last_name: Frischknecht
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Holger
full_name: Schulze, Holger
last_name: Schulze
- first_name: Ralf
full_name: Enz, Ralf
last_name: Enz
citation:
ama: Klotz L, Wendler O, Frischknecht R, Shigemoto R, Schulze H, Enz R. Localization
of group II and III metabotropic glutamate receptors at pre- and postsynaptic
sites of inner hair cell ribbon synapses. FASEB Journal. 2019;33(12):13734-13746.
doi:10.1096/fj.201901543R
apa: Klotz, L., Wendler, O., Frischknecht, R., Shigemoto, R., Schulze, H., &
Enz, R. (2019). Localization of group II and III metabotropic glutamate receptors
at pre- and postsynaptic sites of inner hair cell ribbon synapses. FASEB Journal.
FASEB. https://doi.org/10.1096/fj.201901543R
chicago: Klotz, Lisa, Olaf Wendler, Renato Frischknecht, Ryuichi Shigemoto, Holger
Schulze, and Ralf Enz. “Localization of Group II and III Metabotropic Glutamate
Receptors at Pre- and Postsynaptic Sites of Inner Hair Cell Ribbon Synapses.”
FASEB Journal. FASEB, 2019. https://doi.org/10.1096/fj.201901543R.
ieee: L. Klotz, O. Wendler, R. Frischknecht, R. Shigemoto, H. Schulze, and R. Enz,
“Localization of group II and III metabotropic glutamate receptors at pre- and
postsynaptic sites of inner hair cell ribbon synapses,” FASEB Journal,
vol. 33, no. 12. FASEB, pp. 13734–13746, 2019.
ista: Klotz L, Wendler O, Frischknecht R, Shigemoto R, Schulze H, Enz R. 2019. Localization
of group II and III metabotropic glutamate receptors at pre- and postsynaptic
sites of inner hair cell ribbon synapses. FASEB Journal. 33(12), 13734–13746.
mla: Klotz, Lisa, et al. “Localization of Group II and III Metabotropic Glutamate
Receptors at Pre- and Postsynaptic Sites of Inner Hair Cell Ribbon Synapses.”
FASEB Journal, vol. 33, no. 12, FASEB, 2019, pp. 13734–46, doi:10.1096/fj.201901543R.
short: L. Klotz, O. Wendler, R. Frischknecht, R. Shigemoto, H. Schulze, R. Enz,
FASEB Journal 33 (2019) 13734–13746.
date_created: 2019-12-15T23:00:42Z
date_published: 2019-12-01T00:00:00Z
date_updated: 2026-04-03T09:44:03Z
day: '01'
ddc:
- '571'
- '599'
department:
- _id: RySh
doi: 10.1096/fj.201901543R
external_id:
isi:
- '000507466100054'
pmid:
- '31585509'
file:
- access_level: open_access
checksum: 79e3b72481dc32489911121cf3b7d8d0
content_type: application/pdf
creator: shigemot
date_created: 2020-12-06T17:30:09Z
date_updated: 2020-12-06T17:30:09Z
file_id: '8922'
file_name: Klotz et al 2019 EMBO Reports.pdf
file_size: 4766789
relation: main_file
success: 1
file_date_updated: 2020-12-06T17:30:09Z
has_accepted_license: '1'
intvolume: ' 33'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
page: 13734-13746
pmid: 1
publication: FASEB Journal
publication_identifier:
eissn:
- 1530-6860
publication_status: published
publisher: FASEB
quality_controlled: '1'
scopus_import: '1'
status: public
title: Localization of group II and III metabotropic glutamate receptors at pre- and
postsynaptic sites of inner hair cell ribbon synapses
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 33
year: '2019'
...
---
_id: '7398'
abstract:
- lang: eng
text: 'Transporters of the solute carrier 6 (SLC6) family translocate their cognate
substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters
of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4).
Here, we posited that the transport cycle of individual SLC6 transporters reflects
the physiological requirements they operate under. We tested this hypothesis by
analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine
transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate
glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions
in real time by electrophysiological recordings. Contrary to monoamine transporters,
both GlyTs were found to have a high transport capacity driven by rapid return
of the empty transporter after release of Cl− on the intracellular side. Rapid
cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate
ions and substrate such that their forward transport mode was maintained even
under conditions of elevated intracellular Na+ or Cl−. The most important differences
in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement
and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1
were governed by transition of the substrate-bound transporter from outward- to
inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+
binding (or a related conformational change). Kinetic modeling showed that the
kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels
required for NMDA receptor activation.'
article_processing_charge: No
article_type: original
author:
- first_name: Fatma Asli
full_name: Erdem, Fatma Asli
last_name: Erdem
- first_name: Marija
full_name: Ilic, Marija
last_name: Ilic
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Jakub
full_name: Gołacki, Jakub
last_name: Gołacki
- first_name: Gert
full_name: Lubec, Gert
last_name: Lubec
- first_name: Michael
full_name: Freissmuth, Michael
last_name: Freissmuth
- first_name: Walter
full_name: Sandtner, Walter
last_name: Sandtner
citation:
ama: Erdem FA, Ilic M, Koppensteiner P, et al. A comparison of the transport kinetics
of glycine transporter 1 and glycine transporter 2. The Journal of General
Physiology. 2019;151(8):1035-1050. doi:10.1085/jgp.201912318
apa: Erdem, F. A., Ilic, M., Koppensteiner, P., Gołacki, J., Lubec, G., Freissmuth,
M., & Sandtner, W. (2019). A comparison of the transport kinetics of glycine
transporter 1 and glycine transporter 2. The Journal of General Physiology.
Rockefeller University Press. https://doi.org/10.1085/jgp.201912318
chicago: Erdem, Fatma Asli, Marija Ilic, Peter Koppensteiner, Jakub Gołacki, Gert
Lubec, Michael Freissmuth, and Walter Sandtner. “A Comparison of the Transport
Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” The Journal of
General Physiology. Rockefeller University Press, 2019. https://doi.org/10.1085/jgp.201912318.
ieee: F. A. Erdem et al., “A comparison of the transport kinetics of glycine
transporter 1 and glycine transporter 2,” The Journal of General Physiology,
vol. 151, no. 8. Rockefeller University Press, pp. 1035–1050, 2019.
ista: Erdem FA, Ilic M, Koppensteiner P, Gołacki J, Lubec G, Freissmuth M, Sandtner
W. 2019. A comparison of the transport kinetics of glycine transporter 1 and glycine
transporter 2. The Journal of General Physiology. 151(8), 1035–1050.
mla: Erdem, Fatma Asli, et al. “A Comparison of the Transport Kinetics of Glycine
Transporter 1 and Glycine Transporter 2.” The Journal of General Physiology,
vol. 151, no. 8, Rockefeller University Press, 2019, pp. 1035–50, doi:10.1085/jgp.201912318.
short: F.A. Erdem, M. Ilic, P. Koppensteiner, J. Gołacki, G. Lubec, M. Freissmuth,
W. Sandtner, The Journal of General Physiology 151 (2019) 1035–1050.
date_created: 2020-01-29T16:06:29Z
date_published: 2019-07-03T00:00:00Z
date_updated: 2023-09-07T14:52:23Z
day: '03'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1085/jgp.201912318
external_id:
isi:
- '000478792500008'
pmid:
- '31270129'
file:
- access_level: open_access
checksum: 5706b4ccd74ee3e50bf7ecb2a203df71
content_type: application/pdf
creator: dernst
date_created: 2020-02-05T07:20:32Z
date_updated: 2020-07-14T12:47:57Z
file_id: '7450'
file_name: 2019_JGP_Erdem.pdf
file_size: 2641297
relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
intvolume: ' 151'
isi: 1
issue: '8'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1035-1050
pmid: 1
publication: The Journal of General Physiology
publication_identifier:
eissn:
- 1540-7748
issn:
- 0022-1295
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: A comparison of the transport kinetics of glycine transporter 1 and glycine
transporter 2
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 151
year: '2019'
...
---
_id: '7391'
abstract:
- lang: eng
text: Electron microscopy (EM) is a technology that enables visualization of single
proteins at a nanometer resolution. However, current protein analysis by EM mainly
relies on immunolabeling with gold-particle-conjugated antibodies, which is compromised
by large size of antibody, precluding precise detection of protein location in
biological samples. Here, we develop a specific chemical labeling method for EM
detection of proteins at single-molecular level. Rational design of α-helical
peptide tag and probe structure provided a complementary reaction pair that enabled
specific cysteine conjugation of the tag. The developed chemical labeling with
gold-nanoparticle-conjugated probe showed significantly higher labeling efficiency
and detectability of high-density clusters of tag-fused G protein-coupled receptors
in freeze-fracture replicas compared with immunogold labeling. Furthermore, in
ultrathin sections, the spatial resolution of the chemical labeling was significantly
higher than that of antibody-mediated labeling. These results demonstrate substantial
advantages of the chemical labeling approach for single protein visualization
by EM.
article_processing_charge: No
article_type: original
author:
- first_name: Shigekazu
full_name: Tabata, Shigekazu
id: 4427179E-F248-11E8-B48F-1D18A9856A87
last_name: Tabata
- first_name: Marijo
full_name: Jevtic, Marijo
id: 4BE3BC94-F248-11E8-B48F-1D18A9856A87
last_name: Jevtic
- first_name: Nobutaka
full_name: Kurashige, Nobutaka
last_name: Kurashige
- first_name: Hirokazu
full_name: Fuchida, Hirokazu
last_name: Fuchida
- first_name: Munetsugu
full_name: Kido, Munetsugu
last_name: Kido
- first_name: Kazushi
full_name: Tani, Kazushi
last_name: Tani
- first_name: Naoki
full_name: Zenmyo, Naoki
last_name: Zenmyo
- first_name: Shohei
full_name: Uchinomiya, Shohei
last_name: Uchinomiya
- first_name: Harumi
full_name: Harada, Harumi
id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87
last_name: Harada
orcid: 0000-0001-7429-7896
- first_name: Makoto
full_name: Itakura, Makoto
last_name: Itakura
- first_name: Itaru
full_name: Hamachi, Itaru
last_name: Hamachi
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Akio
full_name: Ojida, Akio
last_name: Ojida
citation:
ama: Tabata S, Jevtic M, Kurashige N, et al. Electron microscopic detection of single
membrane proteins by a specific chemical labeling. iScience. 2019;22(12):256-268.
doi:10.1016/j.isci.2019.11.025
apa: Tabata, S., Jevtic, M., Kurashige, N., Fuchida, H., Kido, M., Tani, K., … Ojida,
A. (2019). Electron microscopic detection of single membrane proteins by a specific
chemical labeling. IScience. Elsevier. https://doi.org/10.1016/j.isci.2019.11.025
chicago: Tabata, Shigekazu, Marijo Jevtic, Nobutaka Kurashige, Hirokazu Fuchida,
Munetsugu Kido, Kazushi Tani, Naoki Zenmyo, et al. “Electron Microscopic Detection
of Single Membrane Proteins by a Specific Chemical Labeling.” IScience.
Elsevier, 2019. https://doi.org/10.1016/j.isci.2019.11.025.
ieee: S. Tabata et al., “Electron microscopic detection of single membrane
proteins by a specific chemical labeling,” iScience, vol. 22, no. 12. Elsevier,
pp. 256–268, 2019.
ista: Tabata S, Jevtic M, Kurashige N, Fuchida H, Kido M, Tani K, Zenmyo N, Uchinomiya
S, Harada H, Itakura M, Hamachi I, Shigemoto R, Ojida A. 2019. Electron microscopic
detection of single membrane proteins by a specific chemical labeling. iScience.
22(12), 256–268.
mla: Tabata, Shigekazu, et al. “Electron Microscopic Detection of Single Membrane
Proteins by a Specific Chemical Labeling.” IScience, vol. 22, no. 12, Elsevier,
2019, pp. 256–68, doi:10.1016/j.isci.2019.11.025.
short: S. Tabata, M. Jevtic, N. Kurashige, H. Fuchida, M. Kido, K. Tani, N. Zenmyo,
S. Uchinomiya, H. Harada, M. Itakura, I. Hamachi, R. Shigemoto, A. Ojida, IScience
22 (2019) 256–268.
corr_author: '1'
date_created: 2020-01-29T15:56:56Z
date_published: 2019-12-20T00:00:00Z
date_updated: 2026-06-29T22:30:04Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1016/j.isci.2019.11.025
ec_funded: 1
external_id:
isi:
- '000504652000020'
pmid:
- '31786521'
file:
- access_level: open_access
checksum: f3e90056a49f09b205b1c4f8c739ffd1
content_type: application/pdf
creator: dernst
date_created: 2020-02-04T10:48:36Z
date_updated: 2020-07-14T12:47:57Z
file_id: '7448'
file_name: 2019_iScience_Tabata.pdf
file_size: 7197776
relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
intvolume: ' 22'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 256-268
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 25CBA828-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '720270'
name: Human Brain Project Specific Grant Agreement 1
publication: iScience
publication_identifier:
issn:
- 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '11393'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Electron microscopic detection of single membrane proteins by a specific chemical
labeling
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 22
year: '2019'
...
---
_id: '163'
abstract:
- lang: eng
text: For ultrafast fixation of biological samples to avoid artifacts, high-pressure
freezing (HPF) followed by freeze substitution (FS) is preferred over chemical
fixation at room temperature. After HPF, samples are maintained at low temperature
during dehydration and fixation, while avoiding damaging recrystallization. This
is a notoriously slow process. McDonald and Webb demonstrated, in 2011, that sample
agitation during FS dramatically reduces the necessary time. Then, in 2015, we
(H.G. and S.R.) introduced an agitation module into the cryochamber of an automated
FS unit and demonstrated that the preparation of algae could be shortened from
days to a couple of hours. We argued that variability in the processing, reproducibility,
and safety issues are better addressed using automated FS units. For dissemination,
we started low-cost manufacturing of agitation modules for two of the most widely
used FS units, the Automatic Freeze Substitution Systems, AFS(1) and AFS2, from
Leica Microsystems, using three dimensional (3D)-printing of the major components.
To test them, several labs independently used the modules on a wide variety of
specimens that had previously been processed by manual agitation, or without agitation.
We demonstrate that automated processing with sample agitation saves time, increases
flexibility with respect to sample requirements and protocols, and produces data
of at least as good quality as other approaches.
article_processing_charge: No
article_type: original
author:
- first_name: Siegfried
full_name: Reipert, Siegfried
last_name: Reipert
- first_name: Helmuth
full_name: Goldammer, Helmuth
last_name: Goldammer
- first_name: Christine
full_name: Richardson, Christine
last_name: Richardson
- first_name: Martin
full_name: Goldberg, Martin
last_name: Goldberg
- first_name: Timothy
full_name: Hawkins, Timothy
last_name: Hawkins
- first_name: Elena
full_name: Hollergschwandtner, Elena
id: 3C054040-F248-11E8-B48F-1D18A9856A87
last_name: Hollergschwandtner
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Sebastian
full_name: Antreich, Sebastian
last_name: Antreich
- first_name: York
full_name: Stierhof, York
last_name: Stierhof
citation:
ama: 'Reipert S, Goldammer H, Richardson C, et al. Agitation modules: Flexible means
to accelerate automated freeze substitution. Journal of Histochemistry and
Cytochemistry. 2018;66(12):903-921. doi:10.1369/0022155418786698'
apa: 'Reipert, S., Goldammer, H., Richardson, C., Goldberg, M., Hawkins, T., Saeckl,
E., … Stierhof, Y. (2018). Agitation modules: Flexible means to accelerate automated
freeze substitution. Journal of Histochemistry and Cytochemistry. SAGE
Publications. https://doi.org/10.1369/0022155418786698'
chicago: 'Reipert, Siegfried, Helmuth Goldammer, Christine Richardson, Martin Goldberg,
Timothy Hawkins, Elena Saeckl, Walter Kaufmann, Sebastian Antreich, and York Stierhof.
“Agitation Modules: Flexible Means to Accelerate Automated Freeze Substitution.”
Journal of Histochemistry and Cytochemistry. SAGE Publications, 2018. https://doi.org/10.1369/0022155418786698.'
ieee: 'S. Reipert et al., “Agitation modules: Flexible means to accelerate
automated freeze substitution,” Journal of Histochemistry and Cytochemistry,
vol. 66, no. 12. SAGE Publications, pp. 903–921, 2018.'
ista: 'Reipert S, Goldammer H, Richardson C, Goldberg M, Hawkins T, Saeckl E, Kaufmann
W, Antreich S, Stierhof Y. 2018. Agitation modules: Flexible means to accelerate
automated freeze substitution. Journal of Histochemistry and Cytochemistry. 66(12),
903–921.'
mla: 'Reipert, Siegfried, et al. “Agitation Modules: Flexible Means to Accelerate
Automated Freeze Substitution.” Journal of Histochemistry and Cytochemistry,
vol. 66, no. 12, SAGE Publications, 2018, pp. 903–21, doi:10.1369/0022155418786698.'
short: S. Reipert, H. Goldammer, C. Richardson, M. Goldberg, T. Hawkins, E. Saeckl,
W. Kaufmann, S. Antreich, Y. Stierhof, Journal of Histochemistry and Cytochemistry
66 (2018) 903–921.
date_created: 2018-12-11T11:44:57Z
date_published: 2018-12-01T00:00:00Z
date_updated: 2026-06-18T17:50:00Z
day: '01'
ddc:
- '570'
department:
- _id: RySh
- _id: EM-Fac
doi: 10.1369/0022155418786698
external_id:
isi:
- '000452277700005'
pmid:
- '29969056'
intvolume: ' 66'
isi: 1
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1369/0022155418786698
month: '12'
oa: 1
oa_version: Published Version
page: 903-921
pmid: 1
publication: Journal of Histochemistry and Cytochemistry
publication_identifier:
issn:
- 0022-1554
publication_status: published
publisher: SAGE Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Agitation modules: Flexible means to accelerate automated freeze substitution'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 66
year: '2018'
...
---
_id: '562'
abstract:
- lang: eng
text: Primary neuronal cell culture preparations are widely used to investigate
synaptic functions. This chapter describes a detailed protocol for the preparation
of a neuronal cell culture in which giant calyx-type synaptic terminals are formed.
This chapter also presents detailed protocols for utilizing the main technical
advantages provided by such a preparation, namely, labeling and imaging of synaptic
organelles and electrophysiological recordings directly from presynaptic terminals.
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
author:
- first_name: Dimitar
full_name: Dimitrov, Dimitar
last_name: Dimitrov
- first_name: Laurent
full_name: Guillaud, Laurent
last_name: Guillaud
- first_name: Kohgaku
full_name: Eguchi, Kohgaku
id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
last_name: Eguchi
orcid: 0000-0002-6170-2546
- first_name: Tomoyuki
full_name: Takahashi, Tomoyuki
last_name: Takahashi
citation:
ama: 'Dimitrov D, Guillaud L, Eguchi K, Takahashi T. Culture of mouse giant central
nervous system synapses and application for imaging and electrophysiological analyses.
In: Skaper SD, ed. Neurotrophic Factors. Vol 1727. Springer; 2018:201-215.
doi:10.1007/978-1-4939-7571-6_15'
apa: Dimitrov, D., Guillaud, L., Eguchi, K., & Takahashi, T. (2018). Culture
of mouse giant central nervous system synapses and application for imaging and
electrophysiological analyses. In S. D. Skaper (Ed.), Neurotrophic Factors
(Vol. 1727, pp. 201–215). Springer. https://doi.org/10.1007/978-1-4939-7571-6_15
chicago: Dimitrov, Dimitar, Laurent Guillaud, Kohgaku Eguchi, and Tomoyuki Takahashi.
“Culture of Mouse Giant Central Nervous System Synapses and Application for Imaging
and Electrophysiological Analyses.” In Neurotrophic Factors, edited by
Stephen D. Skaper, 1727:201–15. Springer, 2018. https://doi.org/10.1007/978-1-4939-7571-6_15.
ieee: D. Dimitrov, L. Guillaud, K. Eguchi, and T. Takahashi, “Culture of mouse giant
central nervous system synapses and application for imaging and electrophysiological
analyses,” in Neurotrophic Factors, vol. 1727, S. D. Skaper, Ed. Springer,
2018, pp. 201–215.
ista: 'Dimitrov D, Guillaud L, Eguchi K, Takahashi T. 2018.Culture of mouse giant
central nervous system synapses and application for imaging and electrophysiological
analyses. In: Neurotrophic Factors. Methods in Molecular Biology, vol. 1727, 201–215.'
mla: Dimitrov, Dimitar, et al. “Culture of Mouse Giant Central Nervous System Synapses
and Application for Imaging and Electrophysiological Analyses.” Neurotrophic
Factors, edited by Stephen D. Skaper, vol. 1727, Springer, 2018, pp. 201–15,
doi:10.1007/978-1-4939-7571-6_15.
short: D. Dimitrov, L. Guillaud, K. Eguchi, T. Takahashi, in:, S.D. Skaper (Ed.),
Neurotrophic Factors, Springer, 2018, pp. 201–215.
date_created: 2018-12-11T11:47:11Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2021-01-12T08:03:05Z
day: '01'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1007/978-1-4939-7571-6_15
editor:
- first_name: Stephen D.
full_name: Skaper, Stephen D.
last_name: Skaper
external_id:
pmid:
- '29222783'
file:
- access_level: open_access
checksum: 8aa174ca65a56fbb19e9f88cff3ac3fd
content_type: application/pdf
creator: dernst
date_created: 2019-11-19T07:47:43Z
date_updated: 2020-07-14T12:47:09Z
file_id: '7046'
file_name: 2018_NeurotrophicFactors_Dimitrov.pdf
file_size: 787407
relation: main_file
file_date_updated: 2020-07-14T12:47:09Z
has_accepted_license: '1'
intvolume: ' 1727'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Submitted Version
page: 201 - 215
pmid: 1
publication: Neurotrophic Factors
publication_status: published
publisher: Springer
publist_id: '7252'
quality_controlled: '1'
scopus_import: 1
status: public
title: Culture of mouse giant central nervous system synapses and application for
imaging and electrophysiological analyses
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1727
year: '2018'
...
---
_id: '326'
abstract:
- lang: eng
text: Three-dimensional (3D) super-resolution microscopy technique structured illumination
microscopy (SIM) imaging of dendritic spines along the dendrite has not been previously
performed in fixed tissues, mainly due to deterioration of the stripe pattern
of the excitation laser induced by light scattering and optical aberrations. To
address this issue and solve these optical problems, we applied a novel clearing
reagent, LUCID, to fixed brains. In SIM imaging, the penetration depth and the
spatial resolution were improved in LUCID-treated slices, and 160-nm spatial resolution
was obtained in a large portion of the imaging volume on a single apical dendrite.
Furthermore, in a morphological analysis of spine heads of layer V pyramidal neurons
(L5PNs) in the medial prefrontal cortex (mPFC) of chronic dexamethasone (Dex)-treated
mice, SIM imaging revealed an altered distribution of spine forms that could not
be detected by high-NA confocal imaging. Thus, super-resolution SIM imaging represents
a promising high-throughput method for revealing spine morphologies in single
dendrites.
acknowledged_ssus:
- _id: EM-Fac
article_processing_charge: No
author:
- first_name: Kazuaki
full_name: Sawada, Kazuaki
last_name: Sawada
- first_name: Ryosuke
full_name: Kawakami, Ryosuke
last_name: Kawakami
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Tomomi
full_name: Nemoto, Tomomi
last_name: Nemoto
citation:
ama: Sawada K, Kawakami R, Shigemoto R, Nemoto T. Super resolution structural analysis
of dendritic spines using three-dimensional structured illumination microscopy
in cleared mouse brain slices. European Journal of Neuroscience. 2018;47(9):1033-1042.
doi:10.1111/ejn.13901
apa: Sawada, K., Kawakami, R., Shigemoto, R., & Nemoto, T. (2018). Super resolution
structural analysis of dendritic spines using three-dimensional structured illumination
microscopy in cleared mouse brain slices. European Journal of Neuroscience.
Wiley. https://doi.org/10.1111/ejn.13901
chicago: Sawada, Kazuaki, Ryosuke Kawakami, Ryuichi Shigemoto, and Tomomi Nemoto.
“Super Resolution Structural Analysis of Dendritic Spines Using Three-Dimensional
Structured Illumination Microscopy in Cleared Mouse Brain Slices.” European
Journal of Neuroscience. Wiley, 2018. https://doi.org/10.1111/ejn.13901.
ieee: K. Sawada, R. Kawakami, R. Shigemoto, and T. Nemoto, “Super resolution structural
analysis of dendritic spines using three-dimensional structured illumination microscopy
in cleared mouse brain slices,” European Journal of Neuroscience, vol.
47, no. 9. Wiley, pp. 1033–1042, 2018.
ista: Sawada K, Kawakami R, Shigemoto R, Nemoto T. 2018. Super resolution structural
analysis of dendritic spines using three-dimensional structured illumination microscopy
in cleared mouse brain slices. European Journal of Neuroscience. 47(9), 1033–1042.
mla: Sawada, Kazuaki, et al. “Super Resolution Structural Analysis of Dendritic
Spines Using Three-Dimensional Structured Illumination Microscopy in Cleared Mouse
Brain Slices.” European Journal of Neuroscience, vol. 47, no. 9, Wiley,
2018, pp. 1033–42, doi:10.1111/ejn.13901.
short: K. Sawada, R. Kawakami, R. Shigemoto, T. Nemoto, European Journal of Neuroscience
47 (2018) 1033–1042.
date_created: 2018-12-11T11:45:50Z
date_published: 2018-03-07T00:00:00Z
date_updated: 2023-09-19T09:58:40Z
day: '07'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1111/ejn.13901
external_id:
isi:
- '000431496400001'
file:
- access_level: open_access
checksum: 98e901d8229e44aa8f3b51d248dedd09
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T16:16:50Z
date_updated: 2020-07-14T12:46:06Z
file_id: '5721'
file_name: 2018_EJN_Sawada.pdf
file_size: 4850261
relation: main_file
file_date_updated: 2020-07-14T12:46:06Z
has_accepted_license: '1'
intvolume: ' 47'
isi: 1
issue: '9'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 1033 - 1042
publication: European Journal of Neuroscience
publication_status: published
publisher: Wiley
publist_id: '7539'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Super resolution structural analysis of dendritic spines using three-dimensional
structured illumination microscopy in cleared mouse brain slices
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 47
year: '2018'
...
---
_id: '41'
abstract:
- lang: eng
text: 'The small-conductance, Ca2+-activated K+ (SK) channel subtype SK2 regulates
the spike rate and firing frequency, as well as Ca2+ transients in Purkinje cells
(PCs). To understand the molecular basis by which SK2 channels mediate these functions,
we analyzed the exact location and densities of SK2 channels along the neuronal
surface of the mouse cerebellar PCs using SDS-digested freeze-fracture replica
labeling (SDS-FRL) of high sensitivity combined with quantitative analyses. Immunogold
particles for SK2 were observed on post- and pre-synaptic compartments showing
both scattered and clustered distribution patterns. We found an axo-somato-dendritic
gradient of the SK2 particle density increasing 12-fold from soma to dendritic
spines. Using two different immunogold approaches, we also found that SK2 immunoparticles
were frequently adjacent to, but never overlap with, the postsynaptic density
of excitatory synapses in PC spines. Co-immunoprecipitation analysis demonstrated
that SK2 channels form macromolecular complexes with two types of proteins that
mobilize Ca2+: CaV2.1 channels and mGlu1α receptors in the cerebellum. Freeze-fracture
replica double-labeling showed significant co-clustering of particles for SK2
with those for CaV2.1 channels and mGlu1α receptors. SK2 channels were also detected
at presynaptic sites, mostly at the presynaptic active zone (AZ), where they are
close to CaV2.1 channels, though they are not significantly co-clustered. These
data demonstrate that SK2 channels located in different neuronal compartments
can associate with distinct proteins mobilizing Ca2+, and suggest that the ultrastructural
association of SK2 with CaV2.1 and mGlu1α provides the mechanism that ensures
voltage (excitability) regulation by distinct intracellular Ca2+ transients in
PCs.'
article_number: '311'
article_processing_charge: No
article_type: original
author:
- first_name: Rafæl
full_name: Luján, Rafæl
last_name: Luján
- first_name: Carolina
full_name: Aguado, Carolina
last_name: Aguado
- first_name: Francisco
full_name: Ciruela, Francisco
last_name: Ciruela
- first_name: Xavier
full_name: Arus, Xavier
last_name: Arus
- first_name: Alejandro
full_name: Martín Belmonte, Alejandro
last_name: Martín Belmonte
- first_name: Rocío
full_name: Alfaro Ruiz, Rocío
last_name: Alfaro Ruiz
- first_name: Jesus
full_name: Martinez Gomez, Jesus
last_name: Martinez Gomez
- first_name: Luis
full_name: De La Ossa, Luis
last_name: De La Ossa
- first_name: Masahiko
full_name: Watanabe, Masahiko
last_name: Watanabe
- first_name: John
full_name: Adelman, John
last_name: Adelman
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
citation:
ama: Luján R, Aguado C, Ciruela F, et al. Sk2 channels associate with mGlu1α receptors
and CaV2.1 channels in Purkinje cells. Frontiers in Cellular Neuroscience.
2018;12. doi:10.3389/fncel.2018.00311
apa: Luján, R., Aguado, C., Ciruela, F., Arus, X., Martín Belmonte, A., Alfaro Ruiz,
R., … Fukazawa, Y. (2018). Sk2 channels associate with mGlu1α receptors and CaV2.1
channels in Purkinje cells. Frontiers in Cellular Neuroscience. Frontiers
Media. https://doi.org/10.3389/fncel.2018.00311
chicago: Luján, Rafæl, Carolina Aguado, Francisco Ciruela, Xavier Arus, Alejandro
Martín Belmonte, Rocío Alfaro Ruiz, Jesus Martinez Gomez, et al. “Sk2 Channels
Associate with MGlu1α Receptors and CaV2.1 Channels in Purkinje Cells.” Frontiers
in Cellular Neuroscience. Frontiers Media, 2018. https://doi.org/10.3389/fncel.2018.00311.
ieee: R. Luján et al., “Sk2 channels associate with mGlu1α receptors and
CaV2.1 channels in Purkinje cells,” Frontiers in Cellular Neuroscience,
vol. 12. Frontiers Media, 2018.
ista: Luján R, Aguado C, Ciruela F, Arus X, Martín Belmonte A, Alfaro Ruiz R, Martinez
Gomez J, De La Ossa L, Watanabe M, Adelman J, Shigemoto R, Fukazawa Y. 2018. Sk2
channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells.
Frontiers in Cellular Neuroscience. 12, 311.
mla: Luján, Rafæl, et al. “Sk2 Channels Associate with MGlu1α Receptors and CaV2.1
Channels in Purkinje Cells.” Frontiers in Cellular Neuroscience, vol. 12,
311, Frontiers Media, 2018, doi:10.3389/fncel.2018.00311.
short: R. Luján, C. Aguado, F. Ciruela, X. Arus, A. Martín Belmonte, R. Alfaro Ruiz,
J. Martinez Gomez, L. De La Ossa, M. Watanabe, J. Adelman, R. Shigemoto, Y. Fukazawa,
Frontiers in Cellular Neuroscience 12 (2018).
date_created: 2018-12-11T11:44:19Z
date_published: 2018-09-19T00:00:00Z
date_updated: 2025-07-10T11:52:35Z
day: '19'
ddc:
- '570'
department:
- _id: RySh
doi: 10.3389/fncel.2018.00311
ec_funded: 1
external_id:
isi:
- '000445090100002'
file:
- access_level: open_access
checksum: 0bcaec8d596162af0b7fe3f31325d480
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T08:49:03Z
date_updated: 2020-07-14T12:46:23Z
file_id: '5684'
file_name: fncel-12-00311.pdf
file_size: 6834251
relation: main_file
file_date_updated: 2020-07-14T12:46:23Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 25CBA828-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '720270'
name: Human Brain Project Specific Grant Agreement 1
publication: Frontiers in Cellular Neuroscience
publication_identifier:
issn:
- 1662-5102
publication_status: published
publisher: Frontiers Media
publist_id: '8013'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje
cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2018'
...
---
_id: '705'
abstract:
- lang: eng
text: Although dopamine receptors D1 and D2 play key roles in hippocampal function,
their synaptic localization within the hippocampus has not been fully elucidated.
In order to understand precise functions of pre- or postsynaptic dopamine receptors
(DRs), the development of protocols to differentiate pre- and postsynaptic DRs
is essential. So far, most studies on determination and quantification of DRs
did not discriminate between subsynaptic localization. Therefore, the aim of the
study was to generate a robust workflow for the localization of DRs. This work
provides the basis for future work on hippocampal DRs, in light that DRs may have
different functions at pre- or postsynaptic sites. Synaptosomes from rat hippocampi
isolated by a sucrose gradient protocol were prepared for super-resolution direct
stochastic optical reconstruction microscopy (dSTORM) using Bassoon as a presynaptic
zone and Homer1 as postsynaptic density marker. Direct labeling of primary validated
antibodies against dopamine receptors D1 (D1R) and D2 (D2R) with Alexa Fluor 594
enabled unequivocal assignment of D1R and D2R to both, pre- and postsynaptic sites.
D1R immunoreactivity clusters were observed within the presynaptic active zone
as well as at perisynaptic sites at the edge of the presynaptic active zone. The
results may be useful for the interpretation of previous studies and the design
of future work on DRs in the hippocampus. Moreover, the reduction of the complexity
of brain tissue by the use of synaptosomal preparations and dSTORM technology
may represent a useful tool for synaptic localization of brain proteins.
article_processing_charge: No
author:
- first_name: Andras
full_name: Miklosi, Andras
last_name: Miklosi
- first_name: Giorgia
full_name: Del Favero, Giorgia
last_name: Del Favero
- first_name: Tanja
full_name: Bulat, Tanja
last_name: Bulat
- first_name: Harald
full_name: Höger, Harald
last_name: Höger
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Doris
full_name: Marko, Doris
last_name: Marko
- first_name: Gert
full_name: Lubec, Gert
last_name: Lubec
citation:
ama: Miklosi A, Del Favero G, Bulat T, et al. Super resolution microscopical localization
of dopamine receptors 1 and 2 in rat hippocampal synaptosomes. Molecular Neurobiology.
2018;55(6):4857 – 4869. doi:10.1007/s12035-017-0688-y
apa: Miklosi, A., Del Favero, G., Bulat, T., Höger, H., Shigemoto, R., Marko, D.,
& Lubec, G. (2018). Super resolution microscopical localization of dopamine
receptors 1 and 2 in rat hippocampal synaptosomes. Molecular Neurobiology.
Springer. https://doi.org/10.1007/s12035-017-0688-y
chicago: Miklosi, Andras, Giorgia Del Favero, Tanja Bulat, Harald Höger, Ryuichi
Shigemoto, Doris Marko, and Gert Lubec. “Super Resolution Microscopical Localization
of Dopamine Receptors 1 and 2 in Rat Hippocampal Synaptosomes.” Molecular Neurobiology.
Springer, 2018. https://doi.org/10.1007/s12035-017-0688-y.
ieee: A. Miklosi et al., “Super resolution microscopical localization of
dopamine receptors 1 and 2 in rat hippocampal synaptosomes,” Molecular Neurobiology,
vol. 55, no. 6. Springer, pp. 4857 – 4869, 2018.
ista: Miklosi A, Del Favero G, Bulat T, Höger H, Shigemoto R, Marko D, Lubec G.
2018. Super resolution microscopical localization of dopamine receptors 1 and
2 in rat hippocampal synaptosomes. Molecular Neurobiology. 55(6), 4857 – 4869.
mla: Miklosi, Andras, et al. “Super Resolution Microscopical Localization of Dopamine
Receptors 1 and 2 in Rat Hippocampal Synaptosomes.” Molecular Neurobiology,
vol. 55, no. 6, Springer, 2018, pp. 4857 – 4869, doi:10.1007/s12035-017-0688-y.
short: A. Miklosi, G. Del Favero, T. Bulat, H. Höger, R. Shigemoto, D. Marko, G.
Lubec, Molecular Neurobiology 55 (2018) 4857 – 4869.
date_created: 2018-12-11T11:48:02Z
date_published: 2018-06-01T00:00:00Z
date_updated: 2023-09-19T09:58:11Z
day: '01'
department:
- _id: RySh
doi: 10.1007/s12035-017-0688-y
external_id:
isi:
- '000431991500025'
intvolume: ' 55'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa_version: None
page: 4857 – 4869
publication: Molecular Neurobiology
publication_status: published
publisher: Springer
publist_id: '6991'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Super resolution microscopical localization of dopamine receptors 1 and 2 in
rat hippocampal synaptosomes
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 55
year: '2018'
...
---
OA_place: publisher
_id: '51'
abstract:
- lang: eng
text: Asymmetries have long been known about in the central nervous system. From
gross anatomical differences, such as the presence of the parapineal organ in
only one hemisphere of the developing zebrafish, to more subtle differences in
activity between both hemispheres, as seen in freely roaming animals or human
participants under PET and fMRI imaging analysis. The presence of asymmetries
has been demonstrated to have huge behavioural implications, with their disruption
often leading to the generation of neurological disorders, memory problems, changes
in personality, and in an organism's health and well-being. For my Ph.D. work
I aimed to tackle two important avenues of research. The first being the process
of input-side dependency in the hippocampus, with the goal of finding a key gene
responsible for its development (Gene X). The second project was to do with experience-induced
laterality formation in the hippocampus. Specifically, how laterality in the synapse
density of the CA1 stratum radiatum (s.r.) could be induced purely through environmental
enrichment. Through unilateral tracer injections into the CA3, I was able to selectively
measure the properties of synapses within the CA1 and investigate how they differed
based upon which hemisphere the presynaptic neurone originated. Having found the
existence of a previously unreported reversed (left-isomerism) i.v. mutant, through
morpholocal examination of labelled terminals in the CA1 s.r., I aimed to elucidate
a key gene responsible for the process of left or right determination of inputs
to the CA1 s.r.. This work relates to the previous finding of input-side dependent
asymmetry in the wild-type rodent, where the origin of the projecting neurone
to the CA1 will determine the morphology of a synapse, to a greater degree than
the hemisphere in which the projection terminates. Using left- and right-isomerism
i.v. mice, in combination with whole genome sequence analysis, I highlight Ena/VASP-like
(Evl) as a potential target for Gene X. In relation to this topic, I also highlight
my work in the recently published paper of how knockout of PirB can lead to a
lack of input-side dependency in the murine hippocampus. For the second question,
I show that the environmental enrichment paradigm will lead to an asymmetry in
the synapse densities in the hippocampus of mice. I also highlight that the nature
of the enrichment is of less consequence than the process of enrichment itself.
I demonstrate that the CA3 region will dramatically alter its projection targets,
in relation to environmental stimulation, with the asymmetry in synaptic density,
caused by enrichment, relying heavily on commissural fibres. I also highlight
the vital importance of input-side dependent asymmetry, as a necessary component
of experience-dependent laterality formation in the CA1 s.r.. However, my results
suggest that it isn't the only cause, as there appears to be a CA1 dependent mechanism
also at play. Upon further investigation, I highlight the significant, and highly
important, finding that the changes seen in the CA1 s.r. were predominantly caused
through projections from the left-CA3, with the right-CA3 having less involvement
in this mechanism.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Matthew J
full_name: Case, Matthew J
id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Case
citation:
ama: 'Case MJ. From the left to the right: A tale of asymmetries, environments,
and hippocampal development. 2018. doi:10.15479/AT:ISTA:th_1032'
apa: 'Case, M. J. (2018). From the left to the right: A tale of asymmetries,
environments, and hippocampal development. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:th_1032'
chicago: 'Case, Matthew J. “From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:th_1032.'
ieee: 'M. J. Case, “From the left to the right: A tale of asymmetries, environments,
and hippocampal development,” Institute of Science and Technology Austria, 2018.'
ista: 'Case MJ. 2018. From the left to the right: A tale of asymmetries, environments,
and hippocampal development. Institute of Science and Technology Austria.'
mla: 'Case, Matthew J. From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development. Institute of Science and Technology Austria,
2018, doi:10.15479/AT:ISTA:th_1032.'
short: 'M.J. Case, From the Left to the Right: A Tale of Asymmetries, Environments,
and Hippocampal Development, Institute of Science and Technology Austria, 2018.'
corr_author: '1'
date_created: 2018-12-11T11:44:22Z
date_published: 2018-06-27T00:00:00Z
date_updated: 2026-04-08T14:13:44Z
day: '27'
ddc:
- '571'
- '576'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:th_1032
file:
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checksum: dcc7b55619d8509dd62b8e99d6cdee44
content_type: application/msword
creator: dernst
date_created: 2019-04-09T07:16:26Z
date_updated: 2021-02-11T23:30:13Z
embargo_to: open_access
file_id: '6251'
file_name: 2018_Thesis_Case_Source.doc
file_size: 141270528
relation: source_file
- access_level: open_access
checksum: f69fdd5c8709c4e618aa8c1a1221153d
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T07:16:23Z
date_updated: 2021-02-11T11:17:14Z
embargo: 2019-07-05
file_id: '6252'
file_name: 2018_Thesis_Case.pdf
file_size: 15193621
relation: main_file
file_date_updated: 2021-02-11T23:30:13Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '186'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8003'
pubrep_id: '1032'
related_material:
record:
- id: '682'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
title: 'From the left to the right: A tale of asymmetries, environments, and hippocampal
development'
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2018'
...
---
_id: '612'
abstract:
- lang: eng
text: Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically
and postsynaptically through the modulation of different effector signalling pathways.
Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested
freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity
for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments,
showing both scattered and clustered distribution patterns. Quantitative analysis
of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles
increasing 26-fold from somata to dendritic spines. To understand the spatial
relationship of GABAB receptors with two key effector ion channels, the G protein-gated
inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel,
biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation
analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels
in the cerebellum. Using double-labelling immunoelectron microscopic techniques,
co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas
they were mainly segregated in the dendritic shafts. In contrast, co-clustering
of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically,
although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was
detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller
in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1
was significantly smaller in the active zone than in the dendritic shafts and
spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in
different subcellular compartments. These data provide a better framework for
understanding the different roles played by GABAB receptors and their effector
ion channels in the cerebellar network.
article_processing_charge: No
article_type: original
author:
- first_name: Rafael
full_name: Luján, Rafael
last_name: Luján
- first_name: Carolina
full_name: Aguado, Carolina
last_name: Aguado
- first_name: Francisco
full_name: Ciruela, Francisco
last_name: Ciruela
- first_name: Javier
full_name: Cózar, Javier
last_name: Cózar
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Luis
full_name: De La Ossa, Luis
last_name: De La Ossa
- first_name: Bernhard
full_name: Bettler, Bernhard
last_name: Bettler
- first_name: Kevin
full_name: Wickman, Kevin
last_name: Wickman
- first_name: Masahiko
full_name: Watanabe, Masahiko
last_name: Watanabe
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
citation:
ama: Luján R, Aguado C, Ciruela F, et al. Differential association of GABAB receptors
with their effector ion channels in Purkinje cells. Brain Structure and Function.
2018;223(3):1565-1587. doi:10.1007/s00429-017-1568-y
apa: Luján, R., Aguado, C., Ciruela, F., Cózar, J., Kleindienst, D., De La Ossa,
L., … Fukazawa, Y. (2018). Differential association of GABAB receptors with their
effector ion channels in Purkinje cells. Brain Structure and Function.
Springer. https://doi.org/10.1007/s00429-017-1568-y
chicago: Luján, Rafael, Carolina Aguado, Francisco Ciruela, Javier Cózar, David
Kleindienst, Luis De La Ossa, Bernhard Bettler, et al. “Differential Association
of GABAB Receptors with Their Effector Ion Channels in Purkinje Cells.” Brain
Structure and Function. Springer, 2018. https://doi.org/10.1007/s00429-017-1568-y.
ieee: R. Luján et al., “Differential association of GABAB receptors with
their effector ion channels in Purkinje cells,” Brain Structure and Function,
vol. 223, no. 3. Springer, pp. 1565–1587, 2018.
ista: Luján R, Aguado C, Ciruela F, Cózar J, Kleindienst D, De La Ossa L, Bettler
B, Wickman K, Watanabe M, Shigemoto R, Fukazawa Y. 2018. Differential association
of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure
and Function. 223(3), 1565–1587.
mla: Luján, Rafael, et al. “Differential Association of GABAB Receptors with Their
Effector Ion Channels in Purkinje Cells.” Brain Structure and Function,
vol. 223, no. 3, Springer, 2018, pp. 1565–87, doi:10.1007/s00429-017-1568-y.
short: R. Luján, C. Aguado, F. Ciruela, J. Cózar, D. Kleindienst, L. De La Ossa,
B. Bettler, K. Wickman, M. Watanabe, R. Shigemoto, Y. Fukazawa, Brain Structure
and Function 223 (2018) 1565–1587.
date_created: 2018-12-11T11:47:29Z
date_published: 2018-04-01T00:00:00Z
date_updated: 2026-06-29T22:31:06Z
day: '01'
ddc:
- '571'
department:
- _id: RySh
doi: 10.1007/s00429-017-1568-y
ec_funded: 1
external_id:
isi:
- '000428419500030'
file:
- access_level: open_access
checksum: a55b3103476ecb5f4f983d8801807e8b
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:15:36Z
date_updated: 2020-07-14T12:47:20Z
file_id: '5157'
file_name: IST-2018-1013-v1+1_2018_Kleindienst_Differential.pdf
file_size: 5542926
relation: main_file
file_date_updated: 2020-07-14T12:47:20Z
has_accepted_license: '1'
intvolume: ' 223'
isi: 1
issue: '3'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1565 - 1587
project:
- _id: 25CBA828-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '720270'
name: Human Brain Project Specific Grant Agreement 1
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Brain Structure and Function
publication_status: published
publisher: Springer
publist_id: '7192'
pubrep_id: '1013'
quality_controlled: '1'
related_material:
record:
- id: '9562'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Differential association of GABAB receptors with their effector ion channels
in Purkinje cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 223
year: '2018'
...
---
_id: '1146'
abstract:
- lang: eng
text: 'Aim: The present study was to compare the effects of nicotinic acid and nicotinamide
on the plasma methyl donors, choline and betaine. Methods: Thirty adult subjects
were randomly divided into three groups of equal size, and orally received purified
water (C group), nicotinic acid (300 mg, NA group) or nicotinamide (300 mg, NM
group). Plasma nicotinamide, N 1-methylnicotinamide, homocysteine, betaine and
choline levels before and 1.5-h and 3-h post-dosing, plasma normetanephrine and
metanephrine concentrations at 3-h post-dosing, and the urinary excretion of N
1-methyl-2-pyridone-5-carboxamide during the test period were examined. Results:
The level of 3-h plasma nicotinamide, N 1-methylnicotinamide, homocysteine, the
urinary excretion of N 1-methyl-2-pyridone-5-carboxamide and pulse pressure (PP)
in the NM group was 221%, 3972%, 61%, 1728% and 21.2% higher than that of the
control group (P < 0.01, except homocysteine and PP P < 0.05), while the
3-h plasma betaine, normetanephrine and metanephrine level in the NM group was
24.4%, 9.4% and 11.7% lower (P < 0.05, except betaine P < 0.01), without
significant difference in choline levels. Similar but less pronounced changes
were observed in the NA group, with a lower level of 3-h plasma N 1-methylnicotinamide
(1.90 ± 0.20 μmol/l vs. 3.62 ± 0.27 μmol/l, P < 0.01) and homocysteine (12.85
± 1.39 μmol/l vs. 18.08 ± 1.02 μmol/l, P < 0.05) but a higher level of betaine
(27.44 ± 0.71 μmol/l vs. 23.52 ± 0.61 μmol/l, P < 0.05) than that of the NM
group. Conclusion: The degradation of nicotinamide consumes more betaine than
that of nicotinic acid at identical doses. This difference should be taken into
consideration in niacin fortification. © 2016 Elsevier Ltd and European Society
for Clinical Nutrition and Metabolism.'
acknowledgement: We thank all the participants for their contribution to this study
and volunteers from the Nursing School of Dalian University for their supporting
to collect blood and urine samples of the participants. We also thank Dr. Yasunori
Takayama from National Institute for Physiological Sciences of Japan for his kind
help.
article_processing_charge: No
author:
- first_name: Wuping
full_name: Sun, Wuping
last_name: Sun
- first_name: Ming-Zhu
full_name: Zhai, Ming-Zhu
id: 34009CFA-F248-11E8-B48F-1D18A9856A87
last_name: Zhai
- first_name: Da
full_name: Li, Da
last_name: Li
- first_name: Yiming
full_name: Zhou, Yiming
last_name: Zhou
- first_name: Nana
full_name: Chen, Nana
last_name: Chen
- first_name: Ming
full_name: Guo, Ming
last_name: Guo
- first_name: Shisheng
full_name: Zhou, Shisheng
last_name: Zhou
citation:
ama: Sun W, Zhai M-Z, Li D, et al. Comparison of the effects of nicotinic acid and
nicotinamide degradation on plasma betaine and choline levels. Clinical Nutrition.
2017;36(4):1136-1142. doi:10.1016/j.clnu.2016.07.016
apa: Sun, W., Zhai, M.-Z., Li, D., Zhou, Y., Chen, N., Guo, M., & Zhou, S. (2017).
Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma
betaine and choline levels. Clinical Nutrition. Elsevier. https://doi.org/10.1016/j.clnu.2016.07.016
chicago: Sun, Wuping, Ming-Zhu Zhai, Da Li, Yiming Zhou, Nana Chen, Ming Guo, and
Shisheng Zhou. “Comparison of the Effects of Nicotinic Acid and Nicotinamide Degradation
on Plasma Betaine and Choline Levels.” Clinical Nutrition. Elsevier, 2017.
https://doi.org/10.1016/j.clnu.2016.07.016.
ieee: W. Sun et al., “Comparison of the effects of nicotinic acid and nicotinamide
degradation on plasma betaine and choline levels,” Clinical Nutrition,
vol. 36, no. 4. Elsevier, pp. 1136–1142, 2017.
ista: Sun W, Zhai M-Z, Li D, Zhou Y, Chen N, Guo M, Zhou S. 2017. Comparison of
the effects of nicotinic acid and nicotinamide degradation on plasma betaine and
choline levels. Clinical Nutrition. 36(4), 1136–1142.
mla: Sun, Wuping, et al. “Comparison of the Effects of Nicotinic Acid and Nicotinamide
Degradation on Plasma Betaine and Choline Levels.” Clinical Nutrition,
vol. 36, no. 4, Elsevier, 2017, pp. 1136–42, doi:10.1016/j.clnu.2016.07.016.
short: W. Sun, M.-Z. Zhai, D. Li, Y. Zhou, N. Chen, M. Guo, S. Zhou, Clinical Nutrition
36 (2017) 1136–1142.
date_created: 2018-12-11T11:50:24Z
date_published: 2017-08-01T00:00:00Z
date_updated: 2025-09-22T09:59:49Z
day: '01'
department:
- _id: RySh
doi: 10.1016/j.clnu.2016.07.016
external_id:
isi:
- '000404315200029'
intvolume: ' 36'
isi: 1
issue: '4'
language:
- iso: eng
month: '08'
oa_version: None
page: 1136-1142
publication: Clinical Nutrition
publication_identifier:
issn:
- 0261-5614
publication_status: published
publisher: Elsevier
publist_id: '6212'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Comparison of the effects of nicotinic acid and nicotinamide degradation on
plasma betaine and choline levels
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 36
year: '2017'
...
---
_id: '627'
abstract:
- lang: eng
text: Beige adipocytes are a new type of recruitable brownish adipocytes, with highly
mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige
adipocytes were found among white adipocytes, especially in subcutaneous white
adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation
of energy metabolism and fat deposition. Transient receptor potential melastatin
8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in
the regulation of various cellular functions. It has been reported that TRPM8
activation enhanced the thermogenic function of brown adiposytes. However, the
involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our
data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein
and functional levels. The mRNA expression of Trpm8 was significantly increased
in the differentiated white adipocytes than pre-adipocytes. Moreover, activation
of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white
aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes
was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In
addition, high fat diet (HFD)-induced obesity in mice was significantly recovered
by co-treatment with menthol. Dietary menthol enhanced WAT "browning"
and improved glucose metabolism in HFD-induced obesity mice as well. Therefore,
we concluded that TRPM8 might be involved in WAT "browning" by increasing
the expression levels of genes related to thermogenesis and energy metabolism.
And dietary menthol could be a novel approach for combating human obesity and
related metabolic diseases.
article_processing_charge: No
author:
- first_name: Changyu
full_name: Jiang, Changyu
last_name: Jiang
- first_name: Ming-Zhu
full_name: Zhai, Ming-Zhu
id: 34009CFA-F248-11E8-B48F-1D18A9856A87
last_name: Zhai
- first_name: Dong
full_name: Yan, Dong
last_name: Yan
- first_name: Da
full_name: Li, Da
last_name: Li
- first_name: Chen
full_name: Li, Chen
last_name: Li
- first_name: Yonghong
full_name: Zhang, Yonghong
last_name: Zhang
- first_name: Lizu
full_name: Xiao, Lizu
last_name: Xiao
- first_name: Donglin
full_name: Xiong, Donglin
last_name: Xiong
- first_name: Qiwen
full_name: Deng, Qiwen
last_name: Deng
- first_name: Wuping
full_name: Sun, Wuping
last_name: Sun
citation:
ama: Jiang C, Zhai M-Z, Yan D, et al. Dietary menthol-induced TRPM8 activation enhances
WAT “browning” and ameliorates diet-induced obesity. Oncotarget. 2017;8(43):75114-75126.
doi:10.18632/oncotarget.20540
apa: Jiang, C., Zhai, M.-Z., Yan, D., Li, D., Li, C., Zhang, Y., … Sun, W. (2017).
Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates
diet-induced obesity. Oncotarget. Impact Journals. https://doi.org/10.18632/oncotarget.20540
chicago: Jiang, Changyu, Ming-Zhu Zhai, Dong Yan, Da Li, Chen Li, Yonghong Zhang,
Lizu Xiao, Donglin Xiong, Qiwen Deng, and Wuping Sun. “Dietary Menthol-Induced
TRPM8 Activation Enhances WAT ‘Browning’ and Ameliorates Diet-Induced Obesity.”
Oncotarget. Impact Journals, 2017. https://doi.org/10.18632/oncotarget.20540.
ieee: C. Jiang et al., “Dietary menthol-induced TRPM8 activation enhances
WAT ‘browning’ and ameliorates diet-induced obesity,” Oncotarget, vol.
8, no. 43. Impact Journals, pp. 75114–75126, 2017.
ista: Jiang C, Zhai M-Z, Yan D, Li D, Li C, Zhang Y, Xiao L, Xiong D, Deng Q, Sun
W. 2017. Dietary menthol-induced TRPM8 activation enhances WAT “browning” and
ameliorates diet-induced obesity. Oncotarget. 8(43), 75114–75126.
mla: Jiang, Changyu, et al. “Dietary Menthol-Induced TRPM8 Activation Enhances WAT
‘Browning’ and Ameliorates Diet-Induced Obesity.” Oncotarget, vol. 8, no.
43, Impact Journals, 2017, pp. 75114–26, doi:10.18632/oncotarget.20540.
short: C. Jiang, M.-Z. Zhai, D. Yan, D. Li, C. Li, Y. Zhang, L. Xiao, D. Xiong,
Q. Deng, W. Sun, Oncotarget 8 (2017) 75114–75126.
date_created: 2018-12-11T11:47:34Z
date_published: 2017-08-24T00:00:00Z
date_updated: 2025-09-11T07:28:59Z
day: '24'
ddc:
- '571'
department:
- _id: RySh
doi: 10.18632/oncotarget.20540
external_id:
isi:
- '000411760400142'
file:
- access_level: open_access
checksum: 2219e5348bbfe1aac2725aa620c33280
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:15Z
date_updated: 2020-07-14T12:47:26Z
file_id: '5201'
file_name: IST-2017-907-v1+1_20540-294640-4-PB.pdf
file_size: 6101606
relation: main_file
file_date_updated: 2020-07-14T12:47:26Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
issue: '43'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 75114 - 75126
publication: Oncotarget
publication_identifier:
issn:
- 1949-2553
publication_status: published
publisher: Impact Journals
publist_id: '7167'
pubrep_id: '907'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates
diet-induced obesity
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 8
year: '2017'
...
---
OA_type: closed access
_id: '643'
abstract:
- lang: eng
text: It has been reported that nicotinamide-overload induces oxidative stress associated
with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This
study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance
tests (GTT) were carried out in adult Sprague-Dawley rats treated with or without
cumulative doses of B vitamins. More specifically, insulin tolerance tests (ITT)
were also carried out in adult Sprague-Dawley rats treated with or without cumulative
doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration
significantly increased the plasma H2O2 levels associated with high insulin levels.
Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration
of nicotinic acid, another form of Vitamin B3, also significantly increased plasma
insulin level and H2O2 generation. Moreover, cumulative administration of nicotinic
acid or nicotinamide impaired glucose metabolism. This study suggested that excess
Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.
article_processing_charge: No
article_type: original
author:
- first_name: Wuping
full_name: Sun, Wuping
last_name: Sun
- first_name: Ming-Zhu
full_name: Zhai, Ming-Zhu
id: 34009CFA-F248-11E8-B48F-1D18A9856A87
last_name: Zhai
- first_name: Qian
full_name: Zhou, Qian
last_name: Zhou
- first_name: Chengrui
full_name: Qian, Chengrui
last_name: Qian
- first_name: Changyu
full_name: Jiang, Changyu
last_name: Jiang
citation:
ama: Sun W, Zhai M-Z, Zhou Q, Qian C, Jiang C. Effects of B vitamins overload on
plasma insulin level and hydrogen peroxide generation in rats. Chinese Journal
of Physiology. 2017;60(4):207-214. doi:10.4077/CJP.2017.BAF469
apa: Sun, W., Zhai, M.-Z., Zhou, Q., Qian, C., & Jiang, C. (2017). Effects of
B vitamins overload on plasma insulin level and hydrogen peroxide generation in
rats. Chinese Journal of Physiology. Chinese Physiological Society. https://doi.org/10.4077/CJP.2017.BAF469
chicago: Sun, Wuping, Ming-Zhu Zhai, Qian Zhou, Chengrui Qian, and Changyu Jiang.
“Effects of B Vitamins Overload on Plasma Insulin Level and Hydrogen Peroxide
Generation in Rats.” Chinese Journal of Physiology. Chinese Physiological
Society, 2017. https://doi.org/10.4077/CJP.2017.BAF469.
ieee: W. Sun, M.-Z. Zhai, Q. Zhou, C. Qian, and C. Jiang, “Effects of B vitamins
overload on plasma insulin level and hydrogen peroxide generation in rats,” Chinese
Journal of Physiology, vol. 60, no. 4. Chinese Physiological Society, pp.
207–214, 2017.
ista: Sun W, Zhai M-Z, Zhou Q, Qian C, Jiang C. 2017. Effects of B vitamins overload
on plasma insulin level and hydrogen peroxide generation in rats. Chinese Journal
of Physiology. 60(4), 207–214.
mla: Sun, Wuping, et al. “Effects of B Vitamins Overload on Plasma Insulin Level
and Hydrogen Peroxide Generation in Rats.” Chinese Journal of Physiology,
vol. 60, no. 4, Chinese Physiological Society, 2017, pp. 207–14, doi:10.4077/CJP.2017.BAF469.
short: W. Sun, M.-Z. Zhai, Q. Zhou, C. Qian, C. Jiang, Chinese Journal of Physiology
60 (2017) 207–214.
date_created: 2018-12-11T11:47:40Z
date_published: 2017-08-31T00:00:00Z
date_updated: 2025-09-11T07:19:13Z
day: '31'
ddc:
- '570'
department:
- _id: RySh
doi: 10.4077/CJP.2017.BAF469
external_id:
isi:
- '000409566300002'
pmid:
- '28847140'
intvolume: ' 60'
isi: 1
issue: '4'
language:
- iso: eng
month: '08'
oa_version: None
page: 207 - 214
pmid: 1
publication: Chinese Journal of Physiology
publication_identifier:
issn:
- 0304-4920
publication_status: published
publisher: Chinese Physiological Society
publist_id: '7142'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Effects of B vitamins overload on plasma insulin level and hydrogen peroxide
generation in rats
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 60
year: '2017'
...