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

## TL;DR

Environmental enrichment reduces food cravings by boosting brain inhibitory cells and suppressing specific brain pathways linked to food cues.

## Contribution

The study identifies cell-type and circuit-specific mechanisms by which environmental enrichment suppresses cue-evoked food seeking.

## Key findings

- Environmental enrichment increases baseline excitability of inhibitory interneurons in the prelimbic cortex.
- Environmental enrichment selectively suppresses recruitment of corticothalamic (PL → PVT) neurons during cue-evoked food seeking.
- Environmental enrichment does not affect corticoaccumbens (PL → NAc) projections during cue exposure.

## Abstract

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.

Environmental enrichment (EE) reduces cue‐evoked sucrose seeking and is accompanied by enhanced inhibitory interneuron excitability and suppressed corticothalamic recruitment in the prelimbic cortex. Using brain slice electrophysiology, retrograde tracing and Fos assays, we show that EE increases baseline excitability of interneurons but not pyramidal cells, and selectively suppresses PL → PVT, but not PL → NAc, projection neurons during cue exposure. These findings reveal cell‐ and circuit‐specific mechanisms underlying EE's anti‐craving effects and modulation of food cue reactivity.