# Cell Type–Specific Encoding of Cocaine‐Conditioned Responses in the Lateral Preoptic Area

## TL;DR

This study shows how different types of neurons in the lateral preoptic area respond to cocaine-related cues in mice, revealing distinct patterns linked to drug-associated behaviors.

## Contribution

The study identifies cell type–specific neural activity patterns in the LPO during cocaine conditioning, linking them to conditioned behavioral outcomes.

## Key findings

- Both glutamatergic and GABAergic neurons in the LPO showed reduced activity in the cocaine-paired chamber after conditioning.
- Only glutamatergic neurons increased activity in the saline-paired chamber, correlating with preference for that context.
- Reduced GABAergic activity was associated with stronger preference for the cocaine-paired chamber.

## Abstract

The lateral preoptic area (LPO) is a functionally heterogeneous hypothalamic structure that is increasingly recognised for its role in motivated and drug‐seeking behaviours. Although prior studies have shown that LPO neurons exhibit diverse activity patterns during cocaine self‐administration, the specific contributions of glutamatergic and GABAergic populations to conditioned responses to cocaine remain unclear. In this study, we recorded the activity of LPO glutamatergic (vglut2‐expressing) and GABAergic (vgat‐expressing) neuronal subpopulations during cocaine conditioning to identify how these cell types respond to drug‐associated cues in awake, behaving mice.

Our results revealed that, after cocaine conditioning, both glutamatergic and GABAergic populations showed reduced activity upon entry into the cocaine‐paired chamber. However, only glutamatergic neurons exhibited increased activity when mice entered the saline‐paired chamber. The magnitude of these activity changes was also correlated with behavioural outcomes: reduced GABAergic activity was associated with greater preference for the cocaine‐paired chamber, whereas stronger glutamatergic responses were associated with greater preference for the saline‐paired chamber.

These findings indicate that LPO GABAergic and glutamatergic neurons exhibit distinct, cell type–specific patterns during cocaine‐conditioned place preference. Rather than indicating opposing motivational states, the results highlight that LPO activity relates to conditioned behaviours in a cell type– and context‐dependent manner. By linking activity in glutamatergic and GABAergic neurons with conditioned responses, this work provides initial evidence for how LPO circuits may contribute to drug‐associated learning.

Cocaine conditioning induces context‐specific and cell type–specific dependent changes in activity in glutamatergic and GABAergic neuronal populations of the lateral preoptic area.