Early- but not late-adolescent Western diet consumption programs for long-lasting memory impairments in male but not female rats.

Early life Western diet (WD) consumption leads to impaired memory function, particularly for processes mediated by the hippocampus. However, the precise critical developmental window(s) during which WD exposure negatively impacts hippocampal function are unknown. Here, we exposed male and female rats to a WD model involving free access to a variety of high-fat and/or high-sugar food and drink items during either the early-adolescent period (postnatal days [PN] 26-41; WD-EA) or late-adolescent period (PN 41-56; WD-LA). Control (CTL) rats were given healthy standard chow throughout both periods. To evaluate long-lasting memory capacity well beyond the early life WD exposure periods, we performed behavioral assessments after both a short (4 weeks for WD-EA, 2 weeks for WD-LA) and long (12 weeks for WD-EA, 10 weeks for WD-LA) period of healthy diet intervention. Results revealed no differences in body weight or body composition between diet groups, regardless of sex. Following the shorter period of healthy diet intervention, both male and female WD-EA and WD-LA rats showed deficits in hippocampal-dependent memory compared to CTL rats. Following the longer healthy diet intervention period, memory impairments persisted in male WD-EA but not WD-LA rats. In contrast, in female rats the longer healthy diet intervention reversed the initial memory impairments in both WD-EA and WD-LA rats. Collectively, these findings reveal that early-adolescence is a critical period of long-lasting hippocampal vulnerability to dietary insults in male but not female rats, thus highlighting developmental- and sex-specific effects mediating the relationship between the early life nutritional environment and long-term cognitive health.

Early- but not late-adolescent Western diet consumption programs for long-lasting memory impairments in male but not female rats.

Early life Western diet (WD) consumption leads to impaired memory function, particularly for processes mediated by the hippocampus. However, the precise critical developmental window(s) during which WD exposure negatively impacts hippocampal function are unknown. Here, we exposed male and female rats to a WD model involving free access to a variety of high-fat and/or high-sugar food and drink items during either the early-adolescent period (postnatal days [PN] 26-41; WD-EA) or late-adolescent period (PN 41-56; WD-LA). Control (CTL) rats were given healthy standard chow throughout both periods. To evaluate long-lasting memory capacity well beyond the early life WD exposure periods, we performed behavioral assessments after both a short (4 weeks for WD-EA, 2 weeks for WD-LA) and long (12 weeks for WD-EA, 10 weeks for WD-LA) period of healthy diet intervention. Results revealed no differences in body weight or body composition between diet groups, regardless of sex. Following the shorter period of healthy diet intervention, both male and female WD-EA and WD-LA rats showed deficits in hippocampal-dependent memory compared to CTL rats. Following the longer healthy diet intervention period, memory impairments persisted in male WD-EA but not WD-LA rats. In contrast, in female rats the longer healthy diet intervention reversed the initial memory impairments in both WD-EA and WD-LA rats. Collectively, these findings reveal that early-adolescence is a critical period of long-lasting hippocampal vulnerability to dietary insults in male but not female rats, thus highlighting developmental- and sex-specific effects mediating the relationship between the early life nutritional environment and long-term cognitive health.

Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats.

The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes in male rats. Specifically, results reveal that MCH neuron Ca2+ activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating, and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.