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.

Thesis Files