Date of Award

11-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Biomedical Sciences

Track

Neuroscience

Research Advisor

Detlef H. Heck, PhD

Committee

John D. Boughter, PhD; Max L. Fletcher, PhD; Megan K. Mulligan, PhD; Shalini Narayana, PhD

Keywords

Cerebellum; Coherence, Oscillations, Phase Amplitude Coupling, Respiration

Abstract

Long known for its role in motor control, it is increasingly clear that the cerebellum is also involved in numerous cognitive and affective behaviors. Though the neuronal mechanism for the role of the cerebellum in cognition is still unclear, there is a consensus that it involves cerebellar interactions with the cerebral cortex. Recent studies suggest that the cerebellum monitors, and possibly coordinates, the precise phase alignment or coherence of neuronal oscillations in cerebral cortical areas. Here, we asked how loss of cerebellar function affects respiratory rhythms and the interactions of local field potential (LFP) oscillations between the lobulus simplex (LS) in the cerebellum, medial prefrontal cortex (mPFC), and dorsal CA1 (dCA1) using multisite in vivo extracellular recordings in freely moving mice. We compared a mouse model of cerebellar ataxia and their littermate controls. The ataxic mice were designed to have a genetically induced loss of Purkinje cell neurotransmission, resulting in an expected repertoire of cerebellar motor deficits. Here we asked whether these mice also have neurophysiological defects that are indicative of cognitive circuit dysfunction. We quantified respiratory interval regularity and rhythmicity, power spectra of LFP oscillations in each structure, the magnitudes of coherence of oscillations and Granger causality between each pair of structures using a nonparametric spectral method, and the phase amplitude coupling (PAC) of LFP oscillations within and between each structure. Resting-state coherence of gamma oscillations between LS and mPFC was significantly increased in ataxic mice relative to their controls. Ataxic animals also showed significantly larger Granger causality from the mPFC to cerebellar LS in gamma frequencies compared to littermate controls. Significant PAC within LS was observed at very high gamma frequencies. Our findings reveal that Purkinje cell neurotransmission is required for normal functional interactions between the cerebellum and cerebral cortex and between cerebral cortical areas involved in cognitive functions, suggesting an involvement of the cerebellum in the modulation or coordination of functional communication between brain areas.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

https://orcid.org/0000-0001-7480-5977

DOI

10.21007/etd.cghs.2022.0605

Additional Files
2022-023-ChapmanB-DOA.pdf (189 kB)
Declaration of Authorship
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