Author ORCID Identifier

0000-0002-7616-5624

Defense Date

2020

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Javier González-Maeso

Second Advisor

Jennifer Wolstenholme

Third Advisor

Roland Pittman

Abstract

Sensorimotor gating impairments are observed across a range of neuropsychiatric conditions. The prepulse inhibition of the acoustic startle response (PPI) is a validated measure of sensorimotor gating. Genetic and pharmacological manipulations in rodents have shown PPI is regulated by specific brain monoaminergic systems. Using genetically heterogeneous NIH-HS rats, we stratified individuals by %PPI. In low PPI animals, we observed elevated mRNA levels of certain neurotransmitter receptors, including metabotropic glutamate receptor Grm2, dopamine receptors Drd1 and Drd2, serotonin receptors Htr1a and Htr2a, and scaffolding protein Homer1, in the frontal cortex (FC) and striatum (STR). We found Drd2 mRNA levels were significantly increased in the low PPI group in STR. Multinomial regression analysis indicated Grm2 in FC and Grm2 and Drd2 in STR predicted PPI group. Additional studies showed a linear relationship between PPI and Grm2 in FC and Drd2 in STR. To explore possible epigenetic regulation of altered gene transcription, we adapted chromatin immunoprecipitation (ChIP) for novel application in frozen brain tissue. We evaluated abundance of acetylated histone H3 (H3ac) and trimethylation of lysine residue 27 of histone H3 (H3K27me3) at regions upstream of gene transcription start sites. No differences in levels of H3ac or H3K27me3 were observed. Studies assessing abundance of other histone modifications are warranted. These efforts may offer insight on how epigenetic modification leads to altered transcription of synaptic plasticity genes regulating sensorimotor gating observed in neuropsychiatric conditions.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

3-17-2020

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