Date of Award

2010

Degree Type

Thesis

Degree Name

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Susanne Schmid

Second Advisor

Dr. Arthur Brown

Third Advisor

Dr. Steven Laviolette

Abstract

Individuals with schizophrenia have impairments in prepulse inhibition of startle (PPI) which correlates with cognitive deficits. Nicotine improves the performance of patients and healthy individuals with PPI deficits on PPI tests. We hypothesized that nicotine directly affect startle-mediating neurons of the caudal pontine recticular nucleus (PnC) of the brainstem using electrophysiological recordings. The data revealed that nicotine (10 pM) increases leak current amplitude, reduces membrane resistance, and depolarizes the resting membrane potential. Nicotine had no significant effect on the EPSC amplitude for neither the trigeminal nor auditory stimulations. All effects were reversed only by a high dose (10 pM) of the a-j nAChR antagonist MLA and a low dose of TMPH (lOOnM; antagonizes all but the a7 nAChR). The effect of nicotine persisted in the presence of cadmium (100 pM), which blocks synaptic transmission. These results confirm the functional expression of nAChRs in the PnC and suggest a role of nAChRs in modulating startle responses directly in the brainstem.

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