Biomedical Sciences ETDs

Publication Date

Summer 5-30-2017

Abstract

Up to 61% of adolescent school aged children with fetal alcohol spectrum disorder (FASD) have been suspended or expelled. Executive function deficits, like dis-inhibition and cognitive inflexibility, have been proposed to be better predictors of behavioral problems then IQ score, which qualifies these individuals for developmental disability and special school programs. Reversal learning, a widely used behavioral paradigm for assessing cognitive flexibility across species, has been shown to be impaired in rodent models of prenatal alcohol exposure (PAE). Here we show that a mouse model with daily maternal drinking, resulting in a BAC of 85 mg/dl throughout gestation, results in maladaptive perseveration, or repetitive incorrect errors, on a visual touch-screen reversal paradigm. Reversal of visual touch screen learning has been shown to be mediated by the orbital frontal cortex (OFC), while associative learning is mediated by the dorsal striatum (DS). However, no studies have addressed the in vivo changes in neural signaling that occur after PAE that result in maladaptive perseveration. Pairing PAE with in vivo electrophysiology we have shown that spike firing changes in the OFC and DS may explain prolonged perseveration, however the magnitude of change suggests they are not the sole underlying mechanism of impaired reversal learning. Our data suggest that during early reversal, decreases in functional connectivity and over coordination of spikes with low frequency oscillations may be driving perseveration in PAE treated mice. Therefore, future treatments should be targeted to increase coordinated activity during executive function tasks to help correct negative repetitive behaviors in FASD individuals.

Keywords

in vivo electrophysiology; prenatal alcohol; reversal; orbital frontal cortex; corticostriatal

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Jonathan Brigman

Second Committee Member

Kevin Caldwell

Third Committee Member

Derek Hamilton

Fourth Committee Member

James Cavanagh

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