Environmental Enrichment Suppresses Food Seeking and Increases Inhibitory Interneuron Excitability While Decreasing Corticothalamic Neuronal Recruitment in the Prelimbic Cortex

Cues such as fast-food advertisements associated with food can provoke food cravings which may lead to unhealthy overeating. To effectively control such cravings, we need to better understand the factors that reduce food cue reactivity and reveal corresponding 'anti-craving' brain mechanisms. We previously reported that access to environmental enrichment (EE), that provides cognitive and physical stimulation in mice, reduced cue-evoked sucrose seeking and prelimbic cortex (PL) neuronal reactivity. To date, the phenotype of PL neurons that undergo EE-induced adaptations has not been fully elucidated. Therefore, we used brain slice electrophysiology to investigate how EE modulated intrinsic excitability in the general population of PL interneurons and pyramidal cells. Additionally, we used retrograde tracing and the neuronal activity marker 'Fos' to investigate how EE modulated cue-evoked recruitment of pyramidal cells projecting to the paraventricular nucleus of the thalamus (PVT) and nucleus accumbens core (NAc). Before the cue-evoked sucrose seeking test, EE increased the general, baseline excitability of inhibitory interneurons, but not pyramidal cells. During cue-evoked sucrose seeking, EE selectively suppressed recruitment of corticothalamic (PL → PVT), but not corticoaccumbens (PL → NAc), projections. Collectively, these findings advance our understanding of EE's 'anti-food-seeking' actions by demonstrating both cell type-specific increases in local inhibitory tone and circuit-specific modulation of PL output pathways.