---
_id: '472'
abstract:
- lang: eng
  text: α-Synuclein is a presynaptic protein the function of which has yet to be identified,
    but its neuronal content increases in patients of synucleinopa-thies including
    Parkinson’s disease. Chronic overexpression of α-synuclein reportedly expresses
    various phenotypes of synaptic dysfunction, but the primary target of its toxicity
    has not been determined. To investigate this, we acutely loaded human recombinant
    α-synuclein or its pathological mutants in their monomeric forms into the calyces
    of Held presynaptic terminals in slices from auditorily mature and immature rats
    of either sex. Membrane capacitance measurements revealed significant and specific
    inhibitory effects of WT monomeric α-synuclein on vesicle endocytosis throughout
    development. However, the α-synuclein A53T mutant affected vesicle endocytosis
    only at immature calyces, where as the A30P mutant had no effect throughout. The
    endocytic impairment by WTα-synuclein was rescued by intraterminal coloading of
    the microtubule (MT) polymerization blocker nocodazole. Furthermore, it was reversibly
    rescued by presynaptically loaded photostatin-1, a pho-toswitcheable inhibitor
    of MT polymerization, inalight-wavelength-dependent manner. Incontrast, endocyticinhibition
    by the A53T mutant at immature calyces was not rescued by nocodazole. Functionally,
    presynaptically loaded WT α-synuclein had no effect on basal synaptic transmission
    evoked at a low frequency, but significantly attenuated exocytosis and impaired
    the fidelity of neurotransmission during prolonged high-frequency stimulation.
    We conclude that monomeric WTα-synuclein primarily inhibits vesicle endocytosis
    via MT overassembly, thereby impairing high-frequency neurotransmission.
author:
- first_name: Kohgaku
  full_name: Eguchi, Kohgaku
  id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
  last_name: Eguchi
  orcid: 0000-0002-6170-2546
- first_name: Zachari
  full_name: Taoufiq, Zachari
  last_name: Taoufiq
- first_name: Oliver
  full_name: Thorn Seshold, Oliver
  last_name: Thorn Seshold
- first_name: Dirk
  full_name: Trauner, Dirk
  last_name: Trauner
- first_name: Masato
  full_name: Hasegawa, Masato
  last_name: Hasegawa
- first_name: Tomoyuki
  full_name: Takahashi, Tomoyuki
  last_name: Takahashi
citation:
  ama: Eguchi K, Taoufiq Z, Thorn Seshold O, Trauner D, Hasegawa M, Takahashi T. Wild-type
    monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via
    tubulin polymerization at the calyx of held. <i>European Journal of Neuroscience</i>.
    2017;37(25):6043-6052. doi:<a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">10.1523/JNEUROSCI.0179-17.2017</a>
  apa: Eguchi, K., Taoufiq, Z., Thorn Seshold, O., Trauner, D., Hasegawa, M., &#38;
    Takahashi, T. (2017). Wild-type monomeric α-synuclein can impair vesicle endocytosis
    and synaptic fidelity via tubulin polymerization at the calyx of held. <i>European
    Journal of Neuroscience</i>. Wiley-Blackwell. <a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">https://doi.org/10.1523/JNEUROSCI.0179-17.2017</a>
  chicago: Eguchi, Kohgaku, Zachari Taoufiq, Oliver Thorn Seshold, Dirk Trauner, Masato
    Hasegawa, and Tomoyuki Takahashi. “Wild-Type Monomeric α-Synuclein Can Impair
    Vesicle Endocytosis and Synaptic Fidelity via Tubulin Polymerization at the Calyx
    of Held.” <i>European Journal of Neuroscience</i>. Wiley-Blackwell, 2017. <a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">https://doi.org/10.1523/JNEUROSCI.0179-17.2017</a>.
  ieee: K. Eguchi, Z. Taoufiq, O. Thorn Seshold, D. Trauner, M. Hasegawa, and T. Takahashi,
    “Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity
    via tubulin polymerization at the calyx of held,” <i>European Journal of Neuroscience</i>,
    vol. 37, no. 25. Wiley-Blackwell, pp. 6043–6052, 2017.
  ista: Eguchi K, Taoufiq Z, Thorn Seshold O, Trauner D, Hasegawa M, Takahashi T.
    2017. Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic
    fidelity via tubulin polymerization at the calyx of held. European Journal of
    Neuroscience. 37(25), 6043–6052.
  mla: Eguchi, Kohgaku, et al. “Wild-Type Monomeric α-Synuclein Can Impair Vesicle
    Endocytosis and Synaptic Fidelity via Tubulin Polymerization at the Calyx of Held.”
    <i>European Journal of Neuroscience</i>, vol. 37, no. 25, Wiley-Blackwell, 2017,
    pp. 6043–52, doi:<a href="https://doi.org/10.1523/JNEUROSCI.0179-17.2017">10.1523/JNEUROSCI.0179-17.2017</a>.
  short: K. Eguchi, Z. Taoufiq, O. Thorn Seshold, D. Trauner, M. Hasegawa, T. Takahashi,
    European Journal of Neuroscience 37 (2017) 6043–6052.
date_created: 2018-12-11T11:46:40Z
date_published: 2017-06-21T00:00:00Z
date_updated: 2021-01-12T08:00:51Z
day: '21'
doi: 10.1523/JNEUROSCI.0179-17.2017
extern: '1'
intvolume: '        37'
issue: '25'
language:
- iso: eng
month: '06'
oa_version: None
page: 6043 - 6052
publication: European Journal of Neuroscience
publication_identifier:
  issn:
  - '02706474'
publication_status: published
publisher: Wiley-Blackwell
publist_id: '7348'
quality_controlled: '1'
status: public
title: Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic
  fidelity via tubulin polymerization at the calyx of held
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 37
year: '2017'
...
---
OA_place: publisher
OA_type: gold
_id: '3443'
abstract:
- lang: eng
  text: In the hippocampal CA1 area, a relatively homogenous population of pyramidal
    cells is accompanied by a diversity of GABAergic interneurons. Previously, we
    found that parvalbumin-expressing basket, axo-axonic, bistratified, and oriens-lacunosum
    moleculare cells, innervating different domains of pyramidal cells, have distinct
    firing patterns during network oscillations in vivo. A second family of interneurons,
    expressing cholecystokinin but not parvalbumin, is known to target the same domains
    of pyramidal cells as do the parvalbumin cells. To test the temporal activity
    of these independent and parallel GABAergic inputs, we recorded the precise spike
    timing of identified cholecystokinin interneurons during hippocampal network oscillations
    in anesthetized rats and determined their molecular expression profiles and synaptic
    targets. The cells were cannabinoid receptor type 1 immunopositive. Contrary to
    the stereotyped firing of parvalbumin interneurons, cholecystokinin-expressing
    basket and dendrite-innervating cells discharge, on average, with 1.7 ± 2.0 Hz
    during high-frequency ripple oscillations in an episode-dependent manner. During
    theta oscillations, cholecystokinin- expressing interneurons fire with 8.8 ± 3.3
    Hz at a characteristic time on the ascending phase of theta waves (155 ± 81°),
    when place cells start firing in freely moving animals. The firing patterns of
    some interneurons recorded in drug-free behaving rats were similar to cholecystokinin
    cells in anesthetized animals. Our results demonstrate that cholecystokinin- and
    parvalbumin-expressing interneurons make different contributions to network oscillations
    and play distinct roles in different brain states. We suggest that the specific
    spike timing of cholecystokinin interneurons and their sensitivity to endocannabinoids
    might contribute to differentiate subgroups of pyramidal cells forming neuronal
    assemblies, whereas parvalbumin interneurons contribute to synchronizing the entire
    network. Copyright © 2005 Society for Neuroscience.
article_processing_charge: No
article_type: original
author:
- first_name: Thomas
  full_name: Klausberger, Thomas
  last_name: Klausberger
- first_name: Laszlo
  full_name: Marton, Laszlo
  last_name: Marton
- first_name: Joseph
  full_name: O'Neill, Joseph
  id: 426376DC-F248-11E8-B48F-1D18A9856A87
  last_name: O'Neill
- first_name: Jojanneke
  full_name: Huck, Jojanneke
  last_name: Huck
- first_name: Yannis
  full_name: Dalezios, Yannis
  last_name: Dalezios
- first_name: Pablo
  full_name: Fuentealba, Pablo
  last_name: Fuentealba
- first_name: Wai
  full_name: Suen, Wai
  last_name: Suen
- first_name: Edit
  full_name: Papp, Edit
  last_name: Papp
- first_name: Takeshi
  full_name: Kaneko, Takeshi
  last_name: Kaneko
- first_name: Masahiko
  full_name: Watanabe, Masahiko
  last_name: Watanabe
- first_name: Jozsef L
  full_name: Csicsvari, Jozsef L
  id: 3FA14672-F248-11E8-B48F-1D18A9856A87
  last_name: Csicsvari
  orcid: 0000-0002-5193-4036
- first_name: Péter
  full_name: Somogyi, Péter
  last_name: Somogyi
citation:
  ama: Klausberger T, Marton L, O’Neill J, et al. Complementary roles of cholecystokinin-
    and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations.
    <i>Journal of Neuroscience</i>. 2005;25(42):9782-9793. doi:<a href="https://doi.org/10.1523/JNEUROSCI.3269-05.2005">10.1523/JNEUROSCI.3269-05.2005</a>
  apa: Klausberger, T., Marton, L., O’Neill, J., Huck, J., Dalezios, Y., Fuentealba,
    P., … Somogyi, P. (2005). Complementary roles of cholecystokinin- and parvalbumin-expressing
    GABAergic neurons in hippocampal network oscillations. <i>Journal of Neuroscience</i>.
    Society for Neuroscience. <a href="https://doi.org/10.1523/JNEUROSCI.3269-05.2005">https://doi.org/10.1523/JNEUROSCI.3269-05.2005</a>
  chicago: Klausberger, Thomas, Laszlo Marton, Joseph O’Neill, Jojanneke Huck, Yannis
    Dalezios, Pablo Fuentealba, Wai Suen, et al. “Complementary Roles of Cholecystokinin-
    and Parvalbumin-Expressing GABAergic Neurons in Hippocampal Network Oscillations.”
    <i>Journal of Neuroscience</i>. Society for Neuroscience, 2005. <a href="https://doi.org/10.1523/JNEUROSCI.3269-05.2005">https://doi.org/10.1523/JNEUROSCI.3269-05.2005</a>.
  ieee: T. Klausberger <i>et al.</i>, “Complementary roles of cholecystokinin- and
    parvalbumin-expressing GABAergic neurons in hippocampal network oscillations,”
    <i>Journal of Neuroscience</i>, vol. 25, no. 42. Society for Neuroscience, pp.
    9782–9793, 2005.
  ista: Klausberger T, Marton L, O’Neill J, Huck J, Dalezios Y, Fuentealba P, Suen
    W, Papp E, Kaneko T, Watanabe M, Csicsvari JL, Somogyi P. 2005. Complementary
    roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal
    network oscillations. Journal of Neuroscience. 25(42), 9782–9793.
  mla: Klausberger, Thomas, et al. “Complementary Roles of Cholecystokinin- and Parvalbumin-Expressing
    GABAergic Neurons in Hippocampal Network Oscillations.” <i>Journal of Neuroscience</i>,
    vol. 25, no. 42, Society for Neuroscience, 2005, pp. 9782–93, doi:<a href="https://doi.org/10.1523/JNEUROSCI.3269-05.2005">10.1523/JNEUROSCI.3269-05.2005</a>.
  short: T. Klausberger, L. Marton, J. O’Neill, J. Huck, Y. Dalezios, P. Fuentealba,
    W. Suen, E. Papp, T. Kaneko, M. Watanabe, J.L. Csicsvari, P. Somogyi, Journal
    of Neuroscience 25 (2005) 9782–9793.
das_tickbox: '1'
date_created: 2018-12-11T12:03:21Z
date_published: 2005-10-19T00:00:00Z
date_updated: 2026-07-01T12:31:21Z
day: '19'
doi: 10.1523/JNEUROSCI.3269-05.2005
extern: '1'
external_id:
  pmid:
  - '16237182'
intvolume: '        25'
issue: '42'
language:
- iso: eng
month: '10'
oa_version: None
page: 9782 - 9793
pmid: 1
publication: Journal of Neuroscience
publication_identifier:
  eissn:
  - 1529-2401
  issn:
  - '02706474'
publication_status: published
publisher: Society for Neuroscience
publist_id: '2944'
status: public
title: Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic
  neurons in hippocampal network oscillations
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 25
year: '2005'
...