Diet and the neurodevelopment of impulsivity

Project Summary Impulsivity refers to the propensity toward rapid action without forethought of the consequences and devaluing rewards that are delayed in time in favor of immediate gratification. Food impulsivity is associated with obesity and binge-eating disorder and can counter efforts to make healthy food choices. Regions of the

brain that regulate food impulsive behaviors, such as the hippocampus and medial prefrontal cortex (mPFC), undergo neuroplasticity during adolescence and emerging evidence indicates that hippocampal-dependent memory is vulnerable to the deleterious impact adolescent consumption of “Western diets” (WD) high in

saturated fat and added sugars. Furthermore, hippocampal dysfunction associated with adolescent WD consumption is not easily reversible by switching to a healthy diet during adulthood. We propose that adolescent consumption of a WD impairs hippocampal development leading to increased impulsive eating

behavior during adulthood. Our unpublished preliminary data are consistent with this hypothesis and show that female rodents fed a WD during adolescence have increased impulsive actions when responding for a palatable food reinforcer during adulthood. Proposed work will extend this model to males and will also

determine whether females and males on a WD during adolescence show a propensity to select smaller and more immediate food rewards over waiting for a larger payoff (delay discounting test of impulsive choice). Our additional preliminary in vivo calcium imaging data reveal differential calcium dynamics in the ventral CA1

hippocampus (vCA1) prior to impulsive vs. non-impulsive food-directed action, with analogous effects observed in the nucleus accumbens shell (ACBsh). Building off these findings, we propose to determine how specific hippocampal circuits (vCA1->mPFC and vCA1->ACBsh) known for their role in modulating reward

behaviors, inhibitory control, and impulsivity, are impacted by an adolescent WD consumption in rats. To determine whether behavioral intervention can reverse the long-lasting increased food impulsivity associated with adolescent WD, we will also investigate whether aerobic exercise, which is known to attenuate WD-

induced hippocampal-dependent memory impairments, can attenuate adolescent WD-induced food impulsive actions and choices. Further, we have previously shown that the incretin hormone glucagon-like peptide-1 (GLP-1) acts on a vCA1->mPFC pathway to reduce food impulsive behavior. Thus, here we propose to

determine whether clinically relevant FDA-approved GLP-1 analogue treatment reverses or attenuates adolescent WD-induced food impulsive behaviors. This proposal is sufficiently powered to determine sex differences for all experiments, and results from these studies will provide a critical contribution to obesity

developmental neuroscience research and advance our understanding of how diet impacts eating behaviors.