Date of Award

2010

Degree Type

Thesis

Degree Name

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. John F MacDonald

Second Advisor

Dr. Vania Prado

Abstract

The hippocampus is a region of the brain known for its role in learning and memory. The neural correlate of memory formation is believed to be changes in synaptic efficacy through processes broadly termed “synaptic plasticity”. Synaptic plasticity includes long term changes that increases (potentiation, LTP) or decreases (depression) synaptic strength. The hippocampus receives modulatory cholinergic afferents originating in the basal forebrain. This project investigates changes in bidirectional synaptic plasticity in gene-modified vesicular acetylcholine transporter protein-knockdown (VAChT-KD) mice, which express decreased acetylcholine secretion. Extracellular field recordings were performed on hippocampal slices to characterize synaptic physiology in the CA1- region glutamatergic synapses. VAChT-KD mice expressed reduced basal transmission and activity-dependent LTP, though depression was not changed. Furthermore, acute application of the cholinergic agonist carbachol rescued the LTP deficit. This project demonstrates that decreased cholinergic tone can affect hippocampal synaptic processes and suggests mechanisms by which cholinergic pathways may act on synapse physiology.

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