Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Neuroscience

Supervisor

Dr. Stan Leung

Abstract

Acetylcholine (Ach) has a fundamental role in cortical activation. The activation of the hippocampus, a cortex implicated in cognitive and sensorimotor functions, is characterized by an increase in power and frequency of oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range. We studied hippocampal activation in two mutant mouse lines with deficiency in cholinergic functionality: VAChT KDHET (HET), and VAChTNkx2.1-Cre-flox/flox (KO). We hypothesized that the mutant mice, relative to wild-type (WT) mice, will manifest abnormal theta and gamma oscillations during different behaviors, and in response to muscarinic cholinergic antagonist scopolamine hydrochloride and to the NMDA receptor glutamatergic antagonist CPP. Local field potentials (LFPs) were recorded from CA1 stratum radiatum in behaving WT and mutant mice before and after injection of drugs. Immobile theta power decreased in the order of WT, HET, and KO. Injection of scopolamine abolished the awake-immobility theta in WT and KO mice, but a theta peak remained in the HET mutant mice. Injection of CPP abolished the awake-immobility theta in HET mice but not in WT and KO mice. Our data suggests that acetylcholine is critical for immobile theta power. The presence of a scopolamine-resistant and CPP-sensitive theta rhythm during awake-immobility in HET mice is a novel finding, since immobility-associated theta rhythm was found to be scopolamine (or atropine) sensitive in WT mice and other laboratory animals. The compensatory changes that activate a scopolamine-resistant, presumably non-cholinergic, theta rhythm during immobility in HET mice remain to be identified.

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