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Resilience of a Precise Motor Behavior

Citation

Torok, Zsofia Erzsebet (2023) Resilience of a Precise Motor Behavior. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/2ff5-e145. https://resolver.caltech.edu/CaltechTHESIS:10122022-003401041

Abstract

Motor memory retention is an essential part of survival and reproduction of most species. However, these behaviors are variable and hard to measure. The zebra finch provides a great model organism to study motor behavior on a fine scale and ask fundamentally important questions. Zebra finch males learn their song from their father and once learnt this song remains unchanged for the remainder of the animals’ life. This highly stereotypic and precise motor function engages a handful of motor nuclei organized in a spatially spread out manner that allows for precise targeting of each key circuit participant for the production of the behavior. In my studies, I focus on better understanding the role of excitatory and inhibitory neurons in the pre-motor nucleus of the song production system. The goal was to perturb the precision of behavioral execution by collapsing the neuronal circuit responsible for sequential activity. Then, to study if the behavior could re-establish in an adult less plastic state of neuronal organization. After I have shown that motor function recovers to produce the same song post disruption, I investigated the large and small scale changes in neuronal activity and transcriptomics accompanying this degradation and recovery trajectory. I have learned that loss of inhibition leads to hyperactivation which eventually leads to a circuit level homeostatic compensation to shut down the pathological activity level. In addition, the upregulation of MHC1 receptors and microglia points to a homeostatic mechanism for synaptic reorganization and re-establishment. Now that we have the means to execute precise cell-type specific manipulations that are reversible and that we understand the underlying phenomenology of perturbation and recovery, we can ask many questions about the architecture of a highly resilient motor pathway. This could shine light on specific electrophysiological and molecular candidates to study for brain damage repair and neurodegenerative research.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:resilience, neuronal plasticity, motor circuit, neuroscience
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Neurobiology
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Lois, Carlos
Thesis Committee:
  • Bronner, Marianne E. (chair)
  • Pachter, Lior S.
  • Siapas, Athanassios G.
  • Lois, Carlos
Defense Date:25 October 2022
Record Number:CaltechTHESIS:10122022-003401041
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:10122022-003401041
DOI:10.7907/2ff5-e145
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2022.09.09.507372DOIbiorXiv publication detailed in Ch. 2 & 4 and added as Appendix C
https://doi.org/10.1101/2022.05.18.492498DOIbiorXiv publication added as Appendix D
ORCID:
AuthorORCID
Torok, Zsofia ErzsebetORCID: 0000-0001-6298-9940
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15040
Collection:CaltechTHESIS
Deposited By: Zsofia Torok
Deposited On:27 Oct 2022 19:00
Last Modified:27 Oct 2022 19:00

Thesis Files

[img] PDF (Full thesis) - Final Version
Restricted to Caltech community only until 26 April 2023.
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44MB
[img] PDF (bioarchive pdf of Appendix D that was added onto main word document) - Supplemental Material
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1MB

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