Date of Award

1-1-2011

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Psychology

Program

Behavioral Neuroscience

Content Description

1 online resource (iii, 134 pages) : illustrations.

Dissertation/Thesis Chair

Robert Rosellini

Committee Members

Bruce Dudek, Christine Wagner

Keywords

affect, attention, folate, inhibitory control, Mthfd1, Prefrontal cortex, Folic acid

Subject Categories

Biological Psychology | Nutrition

Abstract

Folate status plays an essential role in embryogenesis and brain development; however, its importance in supporting cognitive functioning throughout adulthood is less clear. The present study was interested in examining the effects of genetic and dietary alterations in folate status on prefrontal cortical functions in mice, modeling a common polymorphism in the MTHFD1 gene in folate metabolism. A factorial design was used crossing two genotypes (mice with a gene trap insertion in the Mthfd1 gene exhibiting 50% decreased Mthfd1 expression: Mthfd1gt/+ mice or wildtype mice) with two levels of dietary folate (folate sufficient or folate deficient). The mice were tested on a series of visual attention tasks adapted from the 5-choice serial reaction time task to assess learning, attention, inhibitory control, and regulation of emotion/affect. Results revealed dissociable cognitive outcomes depending on the dietary and/or genetic alteration. A folate deficient diet produced a transient but pronounced increase in impulsivity whenever task contingencies changed throughout the task series. In contrast, Mthfd1gt/+ mice showed improved behavioral performance relative to wildtype mice initially in the task series, implicating a compensatory effect that spared cognitive functioning possibly via an increase in methylation capacity. However, an attention deficit was notable for Mthfd1gt/+ mice under more demanding task conditions. Another behavioral pattern seen in the Mthfd1gt/+ mice was a blunted affective response suggestive of a deficit in error-processing or error detection. Importantly, a smaller pilot study showed that choline and acetylcholine metabolism was altered only in Mthfd1gt/+ mice, which could have also contributed to the behavioral patterns seen in these mice. Although a replication study is needed, research of this type is crucial for advancing our understanding of the influence of gene-diet interactions on health outcomes, ultimately informing folate recommendations for individuals with varying genotypes.

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