---
_id: '7878'
abstract:
- lang: eng
text: Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal
signaling. While their function is well documented in slices, requirements for
their activation in vivo are poorly understood. We examine this question in adult
mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons
(MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes
beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s
and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases
Cai rises associated with locomotion. In vitro studies and freeze-fracture electron
microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by
close association of the two classes of receptors. Altogether our results suggest
that mGluR1s, acting in synergy with iGluRs, potently contribute to processing
cerebellar neuronal signaling under physiological conditions.
article_number: e56839
article_processing_charge: No
article_type: original
author:
- first_name: Jin
full_name: Bao, Jin
last_name: Bao
- first_name: Michael
full_name: Graupner, Michael
last_name: Graupner
- first_name: Guadalupe
full_name: Astorga, Guadalupe
last_name: Astorga
- first_name: Thibault
full_name: Collin, Thibault
last_name: Collin
- first_name: Abdelali
full_name: Jalil, Abdelali
last_name: Jalil
- first_name: Dwi Wahyu
full_name: Indriati, Dwi Wahyu
last_name: Indriati
- first_name: Jonathan
full_name: Bradley, Jonathan
last_name: Bradley
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Isabel
full_name: Llano, Isabel
last_name: Llano
citation:
ama: Bao J, Graupner M, Astorga G, et al. Synergism of type 1 metabotropic and ionotropic
glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife.
2020;9. doi:10.7554/eLife.56839
apa: Bao, J., Graupner, M., Astorga, G., Collin, T., Jalil, A., Indriati, D. W.,
… Llano, I. (2020). Synergism of type 1 metabotropic and ionotropic glutamate
receptors in cerebellar molecular layer interneurons in vivo. ELife. eLife
Sciences Publications. https://doi.org/10.7554/eLife.56839
chicago: Bao, Jin, Michael Graupner, Guadalupe Astorga, Thibault Collin, Abdelali
Jalil, Dwi Wahyu Indriati, Jonathan Bradley, Ryuichi Shigemoto, and Isabel Llano.
“Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar
Molecular Layer Interneurons in Vivo.” ELife. eLife Sciences Publications,
2020. https://doi.org/10.7554/eLife.56839.
ieee: J. Bao et al., “Synergism of type 1 metabotropic and ionotropic glutamate
receptors in cerebellar molecular layer interneurons in vivo,” eLife, vol.
9. eLife Sciences Publications, 2020.
ista: Bao J, Graupner M, Astorga G, Collin T, Jalil A, Indriati DW, Bradley J, Shigemoto
R, Llano I. 2020. Synergism of type 1 metabotropic and ionotropic glutamate receptors
in cerebellar molecular layer interneurons in vivo. eLife. 9, e56839.
mla: Bao, Jin, et al. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate
Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife, vol.
9, e56839, eLife Sciences Publications, 2020, doi:10.7554/eLife.56839.
short: J. Bao, M. Graupner, G. Astorga, T. Collin, A. Jalil, D.W. Indriati, J. Bradley,
R. Shigemoto, I. Llano, ELife 9 (2020).
date_created: 2020-05-24T22:00:58Z
date_published: 2020-05-13T00:00:00Z
date_updated: 2023-08-21T06:26:50Z
day: '13'
ddc:
- '570'
department:
- _id: RySh
doi: 10.7554/eLife.56839
external_id:
isi:
- '000535191600001'
pmid:
- '32401196'
file:
- access_level: open_access
checksum: 8ea99bb6660cc407dbdb00c173b01683
content_type: application/pdf
creator: dernst
date_created: 2020-05-26T09:34:54Z
date_updated: 2020-07-14T12:48:04Z
file_id: '7891'
file_name: 2020_eLife_Bao.pdf
file_size: 4832050
relation: main_file
file_date_updated: 2020-07-14T12:48:04Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
eissn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar
molecular layer interneurons in vivo
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: 9
year: '2020'
...
---
_id: '7908'
abstract:
- lang: eng
text: Volatile anesthetics are widely used for surgery, but neuronal mechanisms
of anesthesia remain unidentified. At the calyx of Held in brainstem slices from
rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing
the release probability and the number of readily releasable vesicles. In presynaptic
recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated
exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization,
whereas it inhibited exocytosis evoked by a prolonged depolarization via directly
blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic
depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia
is likely mediated by distinct dual mechanisms, depending on input frequencies.
In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane
impaired the fidelity of repetitive spike transmission, more strongly at higher
frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited
monosynaptic corticocortical spike transmission, preferentially at a higher frequency.
We conclude that dual presynaptic mechanisms operate for the anesthetic action
of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass
filtering role in spike transmission at central excitatory synapses.
article_processing_charge: No
article_type: original
author:
- 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: Takayuki
full_name: Yamashita, Takayuki
last_name: Yamashita
- first_name: Tomoyuki
full_name: Takahashi, Tomoyuki
last_name: Takahashi
citation:
ama: Wang HY, Eguchi K, Yamashita T, Takahashi T. Frequency-dependent block of excitatory
neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of
Neuroscience. 2020;40(21):4103-4115. doi:10.1523/JNEUROSCI.2946-19.2020
apa: Wang, H. Y., Eguchi, K., Yamashita, T., & Takahashi, T. (2020). Frequency-dependent
block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms.
Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.2946-19.2020
chicago: Wang, Han Ying, Kohgaku Eguchi, Takayuki Yamashita, and Tomoyuki Takahashi.
“Frequency-Dependent Block of Excitatory Neurotransmission by Isoflurane via Dual
Presynaptic Mechanisms.” Journal of Neuroscience. Society for Neuroscience,
2020. https://doi.org/10.1523/JNEUROSCI.2946-19.2020.
ieee: H. Y. Wang, K. Eguchi, T. Yamashita, and T. Takahashi, “Frequency-dependent
block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms,”
Journal of Neuroscience, vol. 40, no. 21. Society for Neuroscience, pp.
4103–4115, 2020.
ista: Wang HY, Eguchi K, Yamashita T, Takahashi T. 2020. Frequency-dependent block
of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms.
Journal of Neuroscience. 40(21), 4103–4115.
mla: Wang, Han Ying, et al. “Frequency-Dependent Block of Excitatory Neurotransmission
by Isoflurane via Dual Presynaptic Mechanisms.” Journal of Neuroscience,
vol. 40, no. 21, Society for Neuroscience, 2020, pp. 4103–15, doi:10.1523/JNEUROSCI.2946-19.2020.
short: H.Y. Wang, K. Eguchi, T. Yamashita, T. Takahashi, Journal of Neuroscience
40 (2020) 4103–4115.
date_created: 2020-05-31T22:00:48Z
date_published: 2020-05-20T00:00:00Z
date_updated: 2023-08-21T06:31:25Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.2946-19.2020
external_id:
isi:
- '000535694700004'
file:
- access_level: open_access
checksum: 6571607ea9036154b67cc78e848a7f7d
content_type: application/pdf
creator: dernst
date_created: 2020-06-02T09:12:16Z
date_updated: 2020-07-14T12:48:05Z
file_id: '7912'
file_name: 2020_JourNeuroscience_Wang.pdf
file_size: 3817360
relation: main_file
file_date_updated: 2020-07-14T12:48:05Z
has_accepted_license: '1'
intvolume: ' 40'
isi: 1
issue: '21'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 4103-4115
publication: Journal of Neuroscience
publication_identifier:
eissn:
- '15292401'
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Frequency-dependent block of excitatory neurotransmission by isoflurane via
dual presynaptic mechanisms
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: 40
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>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: 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: '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.
date_created: 2020-02-26T10:56:37Z
date_published: 2020-02-28T00:00:00Z
date_updated: 2023-09-07T13:20:03Z
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
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).
date_created: 2020-09-20T22:01:35Z
date_published: 2020-09-14T00:00:00Z
date_updated: 2024-03-27T23:30:30Z
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:
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- 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'
...