Food seeking suppression by environmental enrichment accompanies cell type- and circuit-specific prelimbic cortical modulation

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 enhanced the general, baseline excitability of inhibitory interneurons, but not pyramidal cells, thereby promoting inhibitory overdrive. During cue-evoked sucrose seeking, EE suppressed recruitment of PVT-, but not NAc-projecting, neurons thereby selectively promoting corticothalamic, but not corticoaccumbens, excitatory underdrive. Collectively, we further illuminate EEs anti-food seeking actions whereby EE promotes both cell type-specific (inhibitory interneuron overdrive) and circuit-specific (excitatory corticothalamic underdrive) neuroadaptations in the PL.