Date of Award

5-2016

Document Type

Honors Thesis

Degree Name

Bachelor of Science

Department

Biological Science

Advisor/Committee Chair

Annalisa Scimemi

Abstract

Obsessive Compulsive disorder (OCD) is a neuropsychiatric disorder characterized by the onset of recurrent thoughts, anxiety, and repetitive motor behaviors. The molecular basis of OCD remains elusive, but recent meta-analysis and genome-wide association studies (GWAS) suggest the existence of a genetic association between polymorphisms in the gene coding for excitatory amino acid carrier 1 (EAAC1) and OCD. It is also known that the Cortico-Striatal-Thalamo-Cortical (CSTC) pathway shows patterned hyperactivity in patients with OCD. EAAC1 is the primary neuronal glutamate transporter in the brain and is abundantly expressed in the cortex and the striatum, two regions that are part of the CTSC pathway. It is currently unknown whether mice that do not express the transporter EAAC1 have a behavioral phenotype consistent with that of OCD in humans, which would make them useful to study the molecular basis of the disease. Through a variety of behavioral tests our research examines phenotypic differences between wild-type C57BL/6 mice and conventional EAAC1 knockout mice (EAAC1-/-) to determine how EAAC1 regulates motor activity, anxiety, and coordinated information processing in the CSTC pathway. Our results suggest that the loss of EAAC1 expression is associated with the onset of motor hyperactivity and anxiety in mice of either sex. These behaviors are reminiscent of the repetitive behaviors and increased anxiety of patients with OCD. Taken together, these findings suggest that EAAC1-/- mice may be a valuable model in which to determine the molecular mechanisms underlying hyperactivity in the CSTC pathway and OCD.

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