Neurochemical Status and Cortical Oscillatory Activity in aGenetic Mouse Model

Date of Award

2020

Degree Name

M.S. in Biology

Department

Department of Biology

Advisor/Chair

Advisor: Pothitos Pitychoutis

Abstract

Calcium (Ca2+) ions comprise critical second messengers for a wide variety of cellularprocesses, including gene expression, cell proliferation and death, and metabolism; neurons are noexception to this. Intraneuronal Ca2+ handling regulates processes such as long-term potentiation(LTP), synaptic transmission, and generation of firing patterns. Subsequently, disruptions ofneuronal Ca2+ has been implicated in several neuropsychiatric and neurodegenerative disorders. Akey component of the neuronal Ca2+ handling toolkit is the sarco/endoplasmic reticulumCa2+ ATPase (SERCA) pump, specifically the SERCA2 isoform. We have recently identified anovel SERCA regulator to be expressed in the central nervous system. In the context of the currentthesis, we assessed how loss of this gene may affect the neurochemical status and the corticaloscillatory activity upon genetic ablation of this gene in mice. Specifically, in the first part of thestudy an ex vivo neurochemical screening in distinct brain regions was conducted using highperformance liquid chromatography (HPLC) with coulometric detection focusing onmonoaminergic (i.e., noradrenaline, serotonin, dopamine) and aminoacidergic neurotransmission(i.e., glutamate, aspartate, ?-aminobutyric acid); in the second part of the study anelectroencephalogram (EEG)-based power spectral analysis was conducted in order to assess howloss of this molecular player affects cortical oscillations in the different vigilance states in micelacking this gene and in their wild type controls. Overall, current findings show that ablation of thisgene results in sex-dependent and brain region-specific endophenotypic alterations and further provide valuable insights to understanding the role of this novel player in brain physiology andpathophysiology.

Keywords

Neurobiology, Neurosciences, Biology, calcium, SERCA2, HPLC, EEG, neurochemistry, power spectral analysis, knockout

Rights Statement

Copyright © 2020, author

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