---
_id: '2018'
abstract:
- lang: eng
  text: Synaptic cell adhesion molecules are increasingly gaining attention for conferring
    specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic
    adhesion molecules that distribute on distinct axons, and their presence restricts
    the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific
    subdendritic segments of target neurons. However, the neural circuits and functional
    roles of netrin-G isoform complexes remain unclear. Here, we use netrin-G-KO and
    NGL-KO mice to reveal that netrin-G1/NGL1 and netrin-G2/NGL2 interactions specify
    excitatory synapses in independent hippocampal pathways. In the hippocampal CA1
    area, netrin-G1/NGL1 and netrin-G2/NGL2 were expressed in the temporoammonic and
    Schaffer collateral pathways, respectively. The lack of presynaptic netrin-Gs
    led to the dispersion of NGLs from postsynaptic membranes. In accord, netrin-G
    mutant synapses displayed opposing phenotypes in long-term and short-term plasticity
    through discrete biochemical pathways. The plasticity phenotypes in netrin-G-KOs
    were phenocopied in NGL-KOs, with a corresponding loss of netrin-Gs from presynaptic
    membranes. Our findings show that netrin-G/NGL interactions differentially control
    synaptic plasticity in distinct circuits via retrograde signaling mechanisms and
    explain how synaptic inputs are diversified to control neuronal activity.
acknowledgement: This work was supported by “Funding Program for World-Leading Innovative
  R&D on Science and Technology (FIRST Program)” initiated by the Council for Science
  and Technology Policy.
article_processing_charge: No
article_type: original
author:
- first_name: Hiroshi
  full_name: Matsukawa, Hiroshi
  last_name: Matsukawa
- first_name: Sachiko
  full_name: Akiyoshi Nishimura, Sachiko
  last_name: Akiyoshi Nishimura
- first_name: Qi
  full_name: Zhang, Qi
  last_name: Zhang
- first_name: Rafael
  full_name: Luján, Rafael
  last_name: Luján
- first_name: Kazuhiko
  full_name: Yamaguchi, Kazuhiko
  last_name: Yamaguchi
- first_name: Hiromichi
  full_name: Goto, Hiromichi
  last_name: Goto
- first_name: Kunio
  full_name: Yaguchi, Kunio
  last_name: Yaguchi
- first_name: Tsutomu
  full_name: Hashikawa, Tsutomu
  last_name: Hashikawa
- first_name: Chie
  full_name: Sano, Chie
  last_name: Sano
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Toshiaki
  full_name: Nakashiba, Toshiaki
  last_name: Nakashiba
- first_name: Shigeyoshi
  full_name: Itohara, Shigeyoshi
  last_name: Itohara
citation:
  ama: Matsukawa H, Akiyoshi Nishimura S, Zhang Q, et al. Netrin-G/NGL complexes encode
    functional synaptic diversification. <i>Journal of Neuroscience</i>. 2014;34(47):15779-15792.
    doi:<a href="https://doi.org/10.1523/JNEUROSCI.1141-14.2014">10.1523/JNEUROSCI.1141-14.2014</a>
  apa: Matsukawa, H., Akiyoshi Nishimura, S., Zhang, Q., Luján, R., Yamaguchi, K.,
    Goto, H., … Itohara, S. (2014). Netrin-G/NGL complexes encode functional synaptic
    diversification. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a
    href="https://doi.org/10.1523/JNEUROSCI.1141-14.2014">https://doi.org/10.1523/JNEUROSCI.1141-14.2014</a>
  chicago: Matsukawa, Hiroshi, Sachiko Akiyoshi Nishimura, Qi Zhang, Rafael Luján,
    Kazuhiko Yamaguchi, Hiromichi Goto, Kunio Yaguchi, et al. “Netrin-G/NGL Complexes
    Encode Functional Synaptic Diversification.” <i>Journal of Neuroscience</i>. Society
    for Neuroscience, 2014. <a href="https://doi.org/10.1523/JNEUROSCI.1141-14.2014">https://doi.org/10.1523/JNEUROSCI.1141-14.2014</a>.
  ieee: H. Matsukawa <i>et al.</i>, “Netrin-G/NGL complexes encode functional synaptic
    diversification,” <i>Journal of Neuroscience</i>, vol. 34, no. 47. Society for
    Neuroscience, pp. 15779–15792, 2014.
  ista: Matsukawa H, Akiyoshi Nishimura S, Zhang Q, Luján R, Yamaguchi K, Goto H,
    Yaguchi K, Hashikawa T, Sano C, Shigemoto R, Nakashiba T, Itohara S. 2014. Netrin-G/NGL
    complexes encode functional synaptic diversification. Journal of Neuroscience.
    34(47), 15779–15792.
  mla: Matsukawa, Hiroshi, et al. “Netrin-G/NGL Complexes Encode Functional Synaptic
    Diversification.” <i>Journal of Neuroscience</i>, vol. 34, no. 47, Society for
    Neuroscience, 2014, pp. 15779–92, doi:<a href="https://doi.org/10.1523/JNEUROSCI.1141-14.2014">10.1523/JNEUROSCI.1141-14.2014</a>.
  short: H. Matsukawa, S. Akiyoshi Nishimura, Q. Zhang, R. Luján, K. Yamaguchi, H.
    Goto, K. Yaguchi, T. Hashikawa, C. Sano, R. Shigemoto, T. Nakashiba, S. Itohara,
    Journal of Neuroscience 34 (2014) 15779–15792.
date_created: 2018-12-11T11:55:14Z
date_published: 2014-11-19T00:00:00Z
date_updated: 2025-09-29T12:00:37Z
day: '19'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.1141-14.2014
external_id:
  isi:
  - '000345907500026'
  pmid:
  - '25411505'
file:
- access_level: open_access
  checksum: 6913e9bc26e9fc1c0441a739a4199229
  content_type: application/pdf
  creator: dernst
  date_created: 2022-05-24T08:41:41Z
  date_updated: 2022-05-24T08:41:41Z
  file_id: '11410'
  file_name: 2014_JournNeuroscience_Matsukawa.pdf
  file_size: 3963728
  relation: main_file
  success: 1
file_date_updated: 2022-05-24T08:41:41Z
has_accepted_license: '1'
intvolume: '        34'
isi: 1
issue: '47'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 15779 - 15792
pmid: 1
publication: Journal of Neuroscience
publication_identifier:
  eissn:
  - 1529-2401
  issn:
  - 0270-6474
publication_status: published
publisher: Society for Neuroscience
publist_id: '5054'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Netrin-G/NGL complexes encode functional synaptic diversification
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 34
year: '2014'
...
---
_id: '2064'
abstract:
- lang: eng
  text: We examined the synaptic structure, quantity, and distribution of α-amino-3-hydroxy-5-methylisoxazole-4-propionic
    acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type glutamate receptors (AMPARs
    and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture
    replica labeling technique. Four excitatory synapses formed by two distinct inputs,
    auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed.
    These excitatory synapse types included AN synapses on bushy cells (AN-BC synapses)
    and fusiform cells (AN-FC synapses) and PF synapses on FC (PF-FC synapses) and
    cartwheel cell spines (PF-CwC synapses). Immunogold labeling revealed differences
    in synaptic structure as well as AMPAR and NMDAR number and/or density in both
    AN and PF synapses, indicating a target-dependent organization. The immunogold
    receptor labeling also identified differences in the synaptic organization of
    FCs based on AN or PF connections, indicating an input-dependent organization
    in FCs. Among the four excitatory synapse types, the AN-BC synapses were the smallest
    and had the most densely packed intramembrane particles (IMPs), whereas the PF-CwC
    synapses were the largest and had sparsely packed IMPs. All four synapse types
    showed positive correlations between the IMP-cluster area and the AMPAR number,
    indicating a common intrasynapse-type relationship for glutamatergic synapses.
    Immunogold particles for AMPARs were distributed over the entire area of individual
    AN synapses; PF synapses often showed synaptic areas devoid of labeling. The gold-labeling
    for NMDARs occurred in a mosaic fashion, with less positive correlations between
    the IMP-cluster area and the NMDAR number. Our observations reveal target- and
    input-dependent features in the structure, number, and organization of AMPARs
    and NMDARs in AN and PF synapses.
acknowledgement: "National Institutes of Health (NIH) Grant Number: 1R01DC013048‐0;
  Biotechnology and Biological Sciences Research Council, UK Grant Number: BB/J015938/1\r\n"
article_processing_charge: No
author:
- first_name: Maía
  full_name: Rubio, Maía
  last_name: Rubio
- first_name: Yugo
  full_name: Fukazawa, Yugo
  last_name: Fukazawa
- first_name: Naomi
  full_name: Kamasawa, Naomi
  last_name: Kamasawa
- first_name: Cheryl
  full_name: Clarkson, Cheryl
  last_name: Clarkson
- first_name: Elek
  full_name: Molnár, Elek
  last_name: Molnár
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  ama: Rubio M, Fukazawa Y, Kamasawa N, Clarkson C, Molnár E, Shigemoto R. Target-
    and input-dependent organization of AMPA and NMDA receptors in synaptic connections
    of the cochlear nucleus. <i>Journal of Comparative Neurology</i>. 2014;522(18):4023-4042.
    doi:<a href="https://doi.org/10.1002/cne.23654">10.1002/cne.23654</a>
  apa: Rubio, M., Fukazawa, Y., Kamasawa, N., Clarkson, C., Molnár, E., &#38; Shigemoto,
    R. (2014). Target- and input-dependent organization of AMPA and NMDA receptors
    in synaptic connections of the cochlear nucleus. <i>Journal of Comparative Neurology</i>.
    Wiley-Blackwell. <a href="https://doi.org/10.1002/cne.23654">https://doi.org/10.1002/cne.23654</a>
  chicago: Rubio, Maía, Yugo Fukazawa, Naomi Kamasawa, Cheryl Clarkson, Elek Molnár,
    and Ryuichi Shigemoto. “Target- and Input-Dependent Organization of AMPA and NMDA
    Receptors in Synaptic Connections of the Cochlear Nucleus.” <i>Journal of Comparative
    Neurology</i>. Wiley-Blackwell, 2014. <a href="https://doi.org/10.1002/cne.23654">https://doi.org/10.1002/cne.23654</a>.
  ieee: M. Rubio, Y. Fukazawa, N. Kamasawa, C. Clarkson, E. Molnár, and R. Shigemoto,
    “Target- and input-dependent organization of AMPA and NMDA receptors in synaptic
    connections of the cochlear nucleus,” <i>Journal of Comparative Neurology</i>,
    vol. 522, no. 18. Wiley-Blackwell, pp. 4023–4042, 2014.
  ista: Rubio M, Fukazawa Y, Kamasawa N, Clarkson C, Molnár E, Shigemoto R. 2014.
    Target- and input-dependent organization of AMPA and NMDA receptors in synaptic
    connections of the cochlear nucleus. Journal of Comparative Neurology. 522(18),
    4023–4042.
  mla: Rubio, Maía, et al. “Target- and Input-Dependent Organization of AMPA and NMDA
    Receptors in Synaptic Connections of the Cochlear Nucleus.” <i>Journal of Comparative
    Neurology</i>, vol. 522, no. 18, Wiley-Blackwell, 2014, pp. 4023–42, doi:<a href="https://doi.org/10.1002/cne.23654">10.1002/cne.23654</a>.
  short: M. Rubio, Y. Fukazawa, N. Kamasawa, C. Clarkson, E. Molnár, R. Shigemoto,
    Journal of Comparative Neurology 522 (2014) 4023–4042.
date_created: 2018-12-11T11:55:30Z
date_published: 2014-07-29T00:00:00Z
date_updated: 2025-09-29T11:47:23Z
day: '29'
department:
- _id: RySh
doi: 10.1002/cne.23654
external_id:
  isi:
  - '000343973100005'
intvolume: '       522'
isi: 1
issue: '18'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198489/
month: '07'
oa: 1
oa_version: Submitted Version
page: 4023 - 4042
publication: Journal of Comparative Neurology
publication_status: published
publisher: Wiley-Blackwell
publist_id: '4974'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Target- and input-dependent organization of AMPA and NMDA receptors in synaptic
  connections of the cochlear nucleus
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 522
year: '2014'
...
