---
_id: '12809'
abstract:
- lang: eng
text: "Understanding the mechanisms of learning and memory formation has always
been one of\r\nthe main goals in neuroscience. Already Pavlov (1927) in his early
days has used his classic\r\nconditioning experiments to study the neural mechanisms
governing behavioral adaptation.\r\nWhat was not known back then was that the
part of the brain that is largely responsible for\r\nthis type of associative
learning is the cerebellum.\r\nSince then, plenty of theories on cerebellar learning
have emerged. Despite their differences,\r\none thing they all have in common
is that learning relies on synaptic and intrinsic plasticity.\r\nThe goal of my
PhD project was to unravel the molecular mechanisms underlying synaptic\r\nplasticity
in two synapses that have been shown to be implicated in motor learning, in an\r\neffort
to understand how learning and memory formation are processed in the cerebellum.\r\nOne
of the earliest and most well-known cerebellar theories postulates that motor
learning\r\nlargely depends on long-term depression at the parallel fiber-Purkinje
cell (PC-PC) synapse.\r\nHowever, the discovery of other types of plasticity in
the cerebellar circuitry, like long-term\r\npotentiation (LTP) at the PC-PC synapse,
potentiation of molecular layer interneurons (MLIs),\r\nand plasticity transfer
from the cortex to the cerebellar/ vestibular nuclei has increased the\r\npopularity
of the idea that multiple sites of plasticity might be involved in learning.\r\nStill
a lot remains unknown about the molecular mechanisms responsible for these types
of\r\nplasticity and whether they occur during physiological learning.\r\nIn the
first part of this thesis we have analyzed the variation and nanodistribution
of voltagegated calcium channels (VGCCs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid\r\ntype glutamate receptors (AMPARs) on the parallel fiber-Purkinje cell
synapse after vestibuloocular reflex phase reversal adaptation, a behavior that
has been suggested to rely on PF-PC\r\nLTP. We have found that on the last day
of adaptation there is no learning trace in form of\r\nVGCCs nor AMPARs variation
at the PF-PC synapse, but instead a decrease in the number of\r\nPF-PC synapses.
These data seem to support the view that learning is only stored in the\r\ncerebellar
cortex in an initial learning phase, being transferred later to the vestibular
nuclei.\r\nNext, we have studied the role of MLIs in motor learning using a relatively
simple and well characterized behavioral paradigm – horizontal optokinetic reflex
(HOKR) adaptation. We\r\nhave found behavior-induced MLI potentiation in form
of release probability increase that\r\ncould be explained by the increase of
VGCCs at the presynaptic side. Our results strengthen\r\nthe idea of distributed
cerebellar plasticity contributing to learning and provide a novel\r\nmechanism
for release probability increase. "
acknowledged_ssus:
- _id: EM-Fac
- _id: Bio
- _id: PreCl
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Catarina
full_name: Alcarva, Catarina
id: 3A96634C-F248-11E8-B48F-1D18A9856A87
last_name: Alcarva
citation:
ama: 'Alcarva C. Plasticity in the cerebellum: What molecular mechanisms are behind
physiological learning. 2023. doi:10.15479/at:ista:12809'
apa: 'Alcarva, C. (2023). Plasticity in the cerebellum: What molecular mechanisms
are behind physiological learning. Institute of Science and Technology Austria.
https://doi.org/10.15479/at:ista:12809'
chicago: 'Alcarva, Catarina. “Plasticity in the Cerebellum: What Molecular Mechanisms
Are behind Physiological Learning.” Institute of Science and Technology Austria,
2023. https://doi.org/10.15479/at:ista:12809.'
ieee: 'C. Alcarva, “Plasticity in the cerebellum: What molecular mechanisms are
behind physiological learning,” Institute of Science and Technology Austria, 2023.'
ista: 'Alcarva C. 2023. Plasticity in the cerebellum: What molecular mechanisms
are behind physiological learning. Institute of Science and Technology Austria.'
mla: 'Alcarva, Catarina. Plasticity in the Cerebellum: What Molecular Mechanisms
Are behind Physiological Learning. Institute of Science and Technology Austria,
2023, doi:10.15479/at:ista:12809.'
short: 'C. Alcarva, Plasticity in the Cerebellum: What Molecular Mechanisms Are
behind Physiological Learning, Institute of Science and Technology Austria, 2023.'
date_created: 2023-04-06T07:54:09Z
date_published: 2023-04-06T00:00:00Z
date_updated: 2023-04-26T12:16:56Z
day: '06'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/at:ista:12809
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file_date_updated: 2023-04-07T06:18:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa_version: Published Version
page: '115'
project:
- _id: 267DFB90-B435-11E9-9278-68D0E5697425
name: 'Plasticity in the cerebellum: Which molecular mechanisms are behind physiological
learning?'
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: 'Plasticity in the cerebellum: What molecular mechanisms are behind physiological
learning'
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '11393'
abstract:
- lang: eng
text: "AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their
role is\r\nimplicated in complex processes such as learning and memory and various
neurological\r\ndiseases. These receptors are composed of different subunits and
the subunit composition can\r\naffect channel properties, receptor trafficking
and interaction with other associated proteins.\r\nUsing the high sensitivity
SDS-digested freeze-fracture replica labeling (SDS-FRL) for\r\nelectron microscopy
I investigated the number, density, and localization of AMPAR subunits,\r\nGluA1,
GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse\r\nhippocampus.
I have found that the immunogold labeling for all of these subunits in the\r\npostsynaptic
sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare.
The labeling density for the all subunits in the extrasynaptic sites showed a
gradual\r\nincrease from the pyramidal cell soma towards the distal part of stratum
radiatum. The densities\r\nof extrasynaptic GluA1, GluA2 and panAMPA labeling
reached 10-15% of synaptic densities,\r\nwhile the ratio of extrasynaptic labeling
for GluA3 was significantly lower compared than those\r\nfor other subunits. The
labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their\r\ndensities
were higher in the periphery than center of synapses. In contrast, the GluA3-\r\ncontaining
receptors were more centrally localized compared to the GluA1- and GluA2-\r\ncontaining
receptors.\r\nThe hippocampus plays a central role in learning and memory. Contextual
learning has been\r\nshown to require the delivery of AMPA receptors to CA1 synapses
in the dorsal hippocampus.\r\nHowever, proximodistal heterogeneity of this plasticity
and particular contribution of different\r\nAMPA receptor subunits are not fully
understood. By combining inhibitory avoidance task, a\r\nhippocampus-dependent
contextual fear-learning paradigm, with SDS-FRL, I have revealed an\r\nincrease
in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area.\r\nThe
intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred\r\npattern.
Furthermore, this synaptic plasticity was evident selectively in stratum radiatum
but\r\nnot stratum oriens, and in the CA1 subregion proximal but not distal to
CA2. These findings\r\nfurther contribute to our understanding of how specific
hippocampal subregions and AMPA\r\nreceptor subunits are involved in physiological
learning.\r\nAlthough the immunolabeling results above shed light on subunit-specific
plasticity in\r\nAMPAR distribution, no tools to visualize and study the subunit
composition at the single\r\nchannel level in situ have been available. Electron
microscopy with conventional immunogold\r\nlabeling approaches has limitations
in the single channel analysis because of the large size of\r\nantibodies and
steric hindrance hampering multiple subunit labeling of single channels. I\r\nmanaged
to develop a new chemical labeling system using a short peptide tag and small\r\nsynthetic
probes, which form specific covalent bond with a cysteine residue in the tag fused
to\r\nproteins of interest (reactive tag system). I additionally made substantial
progress into adapting\r\nthis system for AMPA receptor subunits."
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Marijo
full_name: Jevtic, Marijo
id: 4BE3BC94-F248-11E8-B48F-1D18A9856A87
last_name: Jevtic
citation:
ama: Jevtic M. Contextual fear learning induced changes in AMPA receptor subtypes
along the proximodistal axis in dorsal hippocampus. 2022. doi:10.15479/at:ista:11393
apa: Jevtic, M. (2022). Contextual fear learning induced changes in AMPA receptor
subtypes along the proximodistal axis in dorsal hippocampus. Institute of
Science and Technology Austria. https://doi.org/10.15479/at:ista:11393
chicago: Jevtic, Marijo. “Contextual Fear Learning Induced Changes in AMPA Receptor
Subtypes along the Proximodistal Axis in Dorsal Hippocampus.” Institute of Science
and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11393.
ieee: M. Jevtic, “Contextual fear learning induced changes in AMPA receptor subtypes
along the proximodistal axis in dorsal hippocampus,” Institute of Science and
Technology Austria, 2022.
ista: Jevtic M. 2022. Contextual fear learning induced changes in AMPA receptor
subtypes along the proximodistal axis in dorsal hippocampus. Institute of Science
and Technology Austria.
mla: Jevtic, Marijo. Contextual Fear Learning Induced Changes in AMPA Receptor
Subtypes along the Proximodistal Axis in Dorsal Hippocampus. Institute of
Science and Technology Austria, 2022, doi:10.15479/at:ista:11393.
short: M. Jevtic, Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes
along the Proximodistal Axis in Dorsal Hippocampus, Institute of Science and Technology
Austria, 2022.
date_created: 2022-05-17T08:57:41Z
date_published: 2022-05-16T00:00:00Z
date_updated: 2023-09-07T14:53:44Z
day: '16'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/at:ista:11393
file:
- access_level: closed
checksum: 8fc695d88020d70d231dad0e9f10b138
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: cchlebak
date_created: 2022-05-17T09:08:06Z
date_updated: 2023-05-17T22:30:03Z
embargo_to: open_access
file_id: '11395'
file_name: MJ thesis.docx
file_size: 56427603
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date_created: 2022-05-17T12:09:25Z
date_updated: 2023-05-17T22:30:03Z
embargo: 2023-05-16
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file_size: 4351981
relation: main_file
file_date_updated: 2023-05-17T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '108'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7391'
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: Contextual fear learning induced changes in AMPA receptor subtypes along the
proximodistal axis in dorsal hippocampus
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '9562'
abstract:
- lang: eng
text: Left-right asymmetries can be considered a fundamental organizational principle
of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell
synaptic connection shows an input-side dependent asymmetry where the hemispheric
location of the presynaptic CA3 neuron determines the synaptic properties. Left-input
synapses terminating on apical dendrites in stratum radiatum have a higher density
of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1
and smaller areas with less often perforated PSDs. On the other hand, left-input
synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities
than right-input ones. Apical and basal synapses further employ different signaling
pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize
synaptic membrane proteins with high sensitivity and resolution, and has been
used to reveal the asymmetry at the electron microscopic level. However, it requires
time-consuming manual demarcation of the synaptic surface for quantitative measurements.
To facilitate the analysis of replica labeling, I first developed a software named
Darea, which utilizes deep-learning to automatize this demarcation. With Darea
I characterized the synaptic distribution of NMDA and AMPA receptors as well as
the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I
explored the role of GluN2B and its carboxy-terminus in the establishment of input-side
dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B
expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged
to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were
detected. We further discovered a previously unknown functional asymmetry of GluN2A,
which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus
plays a critical role in normal formation of input-side dependent asymmetry.
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
citation:
ama: 'Kleindienst D. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor
subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning.
2021. doi:10.15479/at:ista:9562'
apa: 'Kleindienst, D. (2021). 2B or not 2B: Hippocampal asymmetries mediated
by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis
by Deep-Learning. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9562'
chicago: 'Kleindienst, David. “2B or Not 2B: Hippocampal Asymmetries Mediated by
NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by
Deep-Learning.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9562.'
ieee: 'D. Kleindienst, “2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor
subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning,”
Institute of Science and Technology Austria, 2021.'
ista: 'Kleindienst D. 2021. 2B or not 2B: Hippocampal asymmetries mediated by NMDA
receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning.
Institute of Science and Technology Austria.'
mla: 'Kleindienst, David. 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA
Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning.
Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9562.'
short: 'D. Kleindienst, 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor
Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning,
Institute of Science and Technology Austria, 2021.'
date_created: 2021-06-17T14:10:47Z
date_published: 2021-06-01T00:00:00Z
date_updated: 2023-09-11T12:55:53Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/at:ista:9562
file:
- access_level: open_access
checksum: 659df5518db495f679cb1df9e9bd1d94
content_type: application/pdf
creator: dkleindienst
date_created: 2021-06-17T14:03:14Z
date_updated: 2022-07-02T22:30:04Z
embargo: 2022-07-01
file_id: '9563'
file_name: Thesis.pdf
file_size: 77299142
relation: main_file
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creator: dkleindienst
date_created: 2021-06-17T14:04:30Z
date_updated: 2022-07-02T22:30:04Z
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file_id: '9564'
file_name: Thesis_source.zip
file_size: 369804895
relation: source_file
file_date_updated: 2022-07-02T22:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '124'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '9756'
relation: part_of_dissertation
status: public
- id: '9437'
relation: part_of_dissertation
status: public
- id: '8532'
relation: part_of_dissertation
status: public
- id: '612'
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: '2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B
C-terminus and high-throughput image analysis by Deep-Learning'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2021'
...
---
_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
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title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
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title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
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keyword:
- Cav2.3
- medial habenula (MHb)
- interpeduncular nucleus (IPN)
language:
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month: '02'
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page: '79'
publication_identifier:
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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: '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.'
date_created: 2018-12-11T11:44:22Z
date_published: 2018-06-27T00:00:00Z
date_updated: 2023-09-07T12:39:22Z
day: '27'
ddc:
- '571'
- '576'
degree_awarded: PhD
department:
- _id: RySh
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supervisor:
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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: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...