Dissertation
Effects of optogenetic theta burst stimulation of the lateral cerebellar nucleus on prelimbic cortex physiology
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2024
DOI: 10.25820/etd.007792
Abstract
Evidence continues to accumulate that through wide-reaching polysynaptic connections, the cerebellum can influence regions of the cerebral cortex that are involved in cognitive processes. Because of this, there is focus on the cerebellum as a therapeutic node for treating cognitive dysfunction. One brain region known to be involved in cognition across mammalian species that is likely manipulated by cerebellar stimulation is the prefrontal cortex. Intermittent theta burst stimulation focused on the cerebellum can influence cognitive functioning in healthy and psychiatric patients. Literature has shown that evoked cerebellar activity can produce observable changes in the rodent prelimbic cortex, a subregion of the medial prefrontal cortex, across a range of physiological measures including electrophysiology and neurotransmitter release. However, little is known about plasticity effects in the prelimbic cortex after intermittent theta burst stimulation of the cerebellum. Here, the lateral cerebellar nucleus in the rat was focally stimulated using optogenetic intermittent theta burst stimulation to focus on electrophysiological, transcriptomic, and dendritic spine changes in response to stimulation to further our understanding of plasticity mechanisms that are at play in cerebellar stimulation. Multisite local field potential recordings were performed in the prelimbic cortex during intermittent theta burst stimulation, with an optrode placed in the LCN for simultaneous recording and stimulation. Separate groups of animals received intermittent theta burst stimulation and brain tissue was collected for gene expression analysis and dendritic spine analysis in the prelimbic cortex. It was revealed that a five-day, twice-daily delivery of optogenetic intermittent theta burst stimulation to the right lateral cerebellar nucleus in rats is capable of evoking a physiological response within the contralateral prelimbic cortex. Effects were limited to the acute timescale, with differences due to stimulation impacting coherence within the theta, beta, and gamma frequencies and synaptic plasticity-related gene expression changes. A longitudinal assessment, measured by a subsequent electrophysiological recording and dendritic spine analysis within the prelimbic cortex, indicated that the stimulation as it was implemented may not induce long-term change. Such results further our understanding of cerebellar intermittent theta burst stimulation, and provide mechanistic insight for the human behavioral changes seen with this stimulation in healthy and neuropsychiatric individuals. This work furthers our understanding of the cerebellum’s interactions with the frontal cortex, and provides a multitude of novel directions to investigate in the cerebellar stimulation space.
Details
- Title: Subtitle
- Effects of optogenetic theta burst stimulation of the lateral cerebellar nucleus on prelimbic cortex physiology
- Creators
- Parker Williamson Abbott
- Contributors
- Krystal L Parker (Advisor)John H Freeman (Committee Member)Rainbo CK Hultman (Committee Member)Jason J Radley (Committee Member)Aislinn J Williams (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Summer 2024
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007792
- Number of pages
- xvii, 169 pages
- Copyright
- Copyright 2024 Parker Williamson Abbott
- Language
- English
- Date submitted
- 05/14/2024
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 142-169).
- Public Abstract (ETD)
The cerebellum is a brain area that has a profound influence on your ability to learn new motor skills. However, evidence continues to show that it is also involved in cognition. Brain disorders that impact the cerebellum can often present with motor impairments but can also present with impairments in cognition, and these symptoms often overlap with brain disorders like schizophrenia and autism spectrum disorder. Evidence has shown that stimulating the cerebellum with non-invasive methods can mediate the cognitive impairments seen in such brain disorders. In this thesis project, I explored a deeper understanding of how stimulation of the cerebellum might impact the frontal cortex, another area of the brain involved in cognition, through experimentation on several features that suggest brain activity changes. I recorded activity within the frontal cortex and cerebellum during stimulation to determine whether features of the brain activity were altered. Additionally, I investigated how genes that play a role in changing the brain were impacted by cerebellar stimulation, and subsequently how changes in dendritic spines, contact points on brain cells that allow them to communicate with other brain cells, could explain why we observe the effects of cerebellar stimulation. These results have important implications for clinical cerebellar stimulation and allow us to understand what changes might occur to alleviate symptoms of cognitive dysfunction in brain disorders like schizophrenia and autism spectrum disorders.
- Academic Unit
- Interdisciplinary Studies Program
- Record Identifier
- 9984698055002771
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