Date of Award

Fall 2011

Degree Type

Thesis

Degree Name

Master of Health Sciences (MSc)

Department

Medical Sciences

Supervisor

Premysl Bercik

Co-Supervisor

Stephen Collins

Language

English

Committee Member

Ram Mishra

Abstract

Emerging evidence indicates that the commensal microbiota communicates with the brain and influences behavior. In animal models, perturbation of the microbiota is accompanied by changes in brain-derived neurotrophic factor (BDNF) levels in the brain. However, underlying mechanisms are unknown. We investigated whether vagal-parasympathetic and sympathetic branches of the autonomic nervous system are involved in the microbiota-gut-brain signalling and attempt to identify specific brain regions that are responsive to alterations in the intestinal microbiota. Specific pathogen-free Balb/c mice, with or without surgical vagotomy or chemical sympathectomy, received oral non-absorbable antimicrobials (ATM) ad libitum for 7 days. Behavior was tested on day 7 in the light/dark preference and step-down latency tests. Specific brain regions were sectioned and stained for the neuronal activation marker, c-fos. Perturbation of the microbiota significantly enhanced the exploratory behavior of mice in both tests and increased the expression of c-fos and phosphorylated c-fos in the hippocampus and dentate gyrus. c-fos expression in the nucleus of the solitary tract was unaffected and neither vagal-parasympathetic nor sympathetic neurotransmission were required for induction of the behavioral change following perturbation of the microbiota. Instability of the commensal microbiota enhances the activation of the hippocampal formation and influences host behavior in a manner that is independent of vagal-parasympathetic and sympathetic autonomic neurotransmission.

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