---
_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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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'
...