---
_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. <i>International Journal of Molecular Sciences</i>. 2020;21(18). doi:<a
    href="https://doi.org/10.3390/ijms21186737">10.3390/ijms21186737</a>
  apa: Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J.,
    Fukazawa, Y., &#38; Shigemoto, R. (2020). Deep learning-assisted high-throughput
    analysis of freeze-fracture replica images applied to glutamate receptors and
    calcium channels at hippocampal synapses. <i>International Journal of Molecular
    Sciences</i>. MDPI. <a href="https://doi.org/10.3390/ijms21186737">https://doi.org/10.3390/ijms21186737</a>
  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.” <i>International Journal
    of Molecular Sciences</i>. MDPI, 2020. <a href="https://doi.org/10.3390/ijms21186737">https://doi.org/10.3390/ijms21186737</a>.
  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,” <i>International Journal of Molecular Sciences</i>,
    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.” <i>International Journal of Molecular Sciences</i>,
    vol. 21, no. 18, 6737, MDPI, 2020, doi:<a href="https://doi.org/10.3390/ijms21186737">10.3390/ijms21186737</a>.
  short: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y.
    Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).
date_created: 2020-09-20T22:01:35Z
date_published: 2020-09-14T00:00:00Z
date_updated: 2024-03-25T23:30:16Z
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 (HBP SGA 2)
publication: International Journal of Molecular Sciences
publication_identifier:
  eissn:
  - '14220067'
  issn:
  - '16616596'
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 21
year: '2020'
...
---
_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&#62;B&#60; receptors in the hippocampus in
    a mouse model of Alzheimer’s disease. <i>Brain Pathology</i>. 2020;30(3):554-575.
    doi:<a href="https://doi.org/10.1111/bpa.12802">10.1111/bpa.12802</a>
  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&#62;B&#60; receptors in the hippocampus in
    a mouse model of Alzheimer’s disease. <i>Brain Pathology</i>. Wiley. <a href="https://doi.org/10.1111/bpa.12802">https://doi.org/10.1111/bpa.12802</a>
  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&#62;B&#60; Receptors
    in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” <i>Brain Pathology</i>.
    Wiley, 2020. <a href="https://doi.org/10.1111/bpa.12802">https://doi.org/10.1111/bpa.12802</a>.
  ieee: A. Martín-Belmonte <i>et al.</i>, “Reduction in the neuronal surface of post
    and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model
    of Alzheimer’s disease,” <i>Brain Pathology</i>, 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&#62;B&#60;
    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&#62;B&#60; Receptors in the Hippocampus in a Mouse Model
    of Alzheimer’s Disease.” <i>Brain Pathology</i>, vol. 30, no. 3, Wiley, 2020,
    pp. 554–75, doi:<a href="https://doi.org/10.1111/bpa.12802">10.1111/bpa.12802</a>.
  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: 2023-09-06T14:48:01Z
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 (HBP SGA 1)
- _id: 26436750-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '785907'
  name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)
publication: Brain Pathology
publication_identifier:
  eissn:
  - '17503639'
  issn:
  - '10156305'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 30
year: '2020'
...
---
_id: '31'
abstract:
- lang: eng
  text: Correlations in sensory neural networks have both extrinsic and intrinsic
    origins. Extrinsic or stimulus correlations arise from shared inputs to the network
    and, thus, depend strongly on the stimulus ensemble. Intrinsic or noise correlations
    reflect biophysical mechanisms of interactions between neurons, which are expected
    to be robust to changes in the stimulus ensemble. Despite the importance of this
    distinction for understanding how sensory networks encode information collectively,
    no method exists to reliably separate intrinsic interactions from extrinsic correlations
    in neural activity data, limiting our ability to build predictive models of the
    network response. In this paper we introduce a general strategy to infer population
    models of interacting neurons that collectively encode stimulus information. The
    key to disentangling intrinsic from extrinsic correlations is to infer the couplings
    between neurons separately from the encoding model and to combine the two using
    corrections calculated in a mean-field approximation. We demonstrate the effectiveness
    of this approach in retinal recordings. The same coupling network is inferred
    from responses to radically different stimulus ensembles, showing that these couplings
    indeed reflect stimulus-independent interactions between neurons. The inferred
    model predicts accurately the collective response of retinal ganglion cell populations
    as a function of the stimulus.
acknowledgement: This work was supported by ANR Trajectory, the French State program
  Investissements d’Avenir managed by the Agence Nationale de la Recherche (LIFESENSES;
  ANR-10-LABX-65), EC Grant No. H2020-785907 from the Human Brain Project, NIH Grant
  No. U01NS090501, and an AVIESAN-UNADEV grant to O.M. M.C. was supported by the Agence
  Nationale de la Recherche Jeune Chercheur/Jeune Chercheuse grant (ANR-17-CE37-0013).
article_number: '042410'
article_processing_charge: No
article_type: original
author:
- first_name: Ulisse
  full_name: Ferrari, Ulisse
  last_name: Ferrari
- first_name: Stephane
  full_name: Deny, Stephane
  last_name: Deny
- first_name: Matthew J
  full_name: Chalk, Matthew J
  last_name: Chalk
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
- first_name: Olivier
  full_name: Marre, Olivier
  last_name: Marre
- first_name: Thierry
  full_name: Mora, Thierry
  last_name: Mora
citation:
  ama: Ferrari U, Deny S, Chalk MJ, Tkačik G, Marre O, Mora T. Separating intrinsic
    interactions from extrinsic correlations in a network of sensory neurons. <i>Physical
    Review E</i>. 2018;98(4). doi:<a href="https://doi.org/10.1103/PhysRevE.98.042410">10.1103/PhysRevE.98.042410</a>
  apa: Ferrari, U., Deny, S., Chalk, M. J., Tkačik, G., Marre, O., &#38; Mora, T.
    (2018). Separating intrinsic interactions from extrinsic correlations in a network
    of sensory neurons. <i>Physical Review E</i>. American Physical Society. <a href="https://doi.org/10.1103/PhysRevE.98.042410">https://doi.org/10.1103/PhysRevE.98.042410</a>
  chicago: Ferrari, Ulisse, Stephane Deny, Matthew J Chalk, Gašper Tkačik, Olivier
    Marre, and Thierry Mora. “Separating Intrinsic Interactions from Extrinsic Correlations
    in a Network of Sensory Neurons.” <i>Physical Review E</i>. American Physical
    Society, 2018. <a href="https://doi.org/10.1103/PhysRevE.98.042410">https://doi.org/10.1103/PhysRevE.98.042410</a>.
  ieee: U. Ferrari, S. Deny, M. J. Chalk, G. Tkačik, O. Marre, and T. Mora, “Separating
    intrinsic interactions from extrinsic correlations in a network of sensory neurons,”
    <i>Physical Review E</i>, vol. 98, no. 4. American Physical Society, 2018.
  ista: Ferrari U, Deny S, Chalk MJ, Tkačik G, Marre O, Mora T. 2018. Separating intrinsic
    interactions from extrinsic correlations in a network of sensory neurons. Physical
    Review E. 98(4), 042410.
  mla: Ferrari, Ulisse, et al. “Separating Intrinsic Interactions from Extrinsic Correlations
    in a Network of Sensory Neurons.” <i>Physical Review E</i>, vol. 98, no. 4, 042410,
    American Physical Society, 2018, doi:<a href="https://doi.org/10.1103/PhysRevE.98.042410">10.1103/PhysRevE.98.042410</a>.
  short: U. Ferrari, S. Deny, M.J. Chalk, G. Tkačik, O. Marre, T. Mora, Physical Review
    E 98 (2018).
date_created: 2018-12-11T11:44:15Z
date_published: 2018-10-17T00:00:00Z
date_updated: 2023-09-18T09:18:44Z
day: '17'
department:
- _id: GaTk
doi: 10.1103/PhysRevE.98.042410
ec_funded: 1
external_id:
  isi:
  - '000447486100004'
intvolume: '        98'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.biorxiv.org/content/10.1101/243816v2.full
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 26436750-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '785907'
  name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)
publication: Physical Review E
publication_identifier:
  issn:
  - '24700045'
publication_status: published
publisher: American Physical Society
publist_id: '8024'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Separating intrinsic interactions from extrinsic correlations in a network
  of sensory neurons
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 98
year: '2018'
...