Fatty Acids and Preclinical Models of Psychiatric Disorders

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DESCRIPTION (provided by applicant): Deficiency in dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) negatively impacts cognitive and affective functioning. A plethora of psychopathology literature also implicates n-3 PUFA deficiency in psychiatric disorders, including mood disorders and schizophrenia. Thus, defining potential neuronal mechanisms that link n-3 PUFA levels to behavioral deficits has important implications for basic neuroscience, as well as for public health, given that the trend of the modern diet has been toward reduced n-3 PUFA intake. The overarching objective of this exploratory R21 application is to move a field, which is becoming increasingly relevant to mental health, forward from the phenomenological stage to delineating brain mechanisms. We propose to use a rodent model to gain mechanistic understanding of the impact of n-3 PUFA deficiency and supplementation on coordinated neuronal activity of the prefrontal cortex (PFC) and ventral striatum (vStr) of adolescent rats. We have found subtle behavioral impairments in n-3 PUFA deficient adolescent rats, suggestive of disrupted motivational and attentional processing. Electrophysiological recordings of single unit activity and local field potentials (LFPs) in PFC subregions and vStr of behaviorally engaged adolescent rats will be made during a reward driven learning task to address two hypotheses: (1) n-3 PUFA deficiency disrupts the dynamics of neuronal activity in the PFC and ventral striatum in response to salient task relevant events, (2) These cellular disruptions are ameliorated with n-3 PUFA supplementation. It is anticipated that the results of these studies will increase our mechanistic understanding of the functional circuitry that influences the behavioral effects of n-3 PUFA deficiency and supplementation. PUBLIC HEALTH RELEVANCE: Through the use of animal models and innovative methodology, this project will increase our mechanistic understanding of how omega -3 supplementation may serve as protective intervention in individuals with psychiatric disease vulnerability.