# Motivating Effects of Negative-hedonic Valence Encoded in Engrams

## TL;DR

This study explores how the brain forms associations between negative emotions and environmental cues, leading to compulsive behaviors like alcohol seeking.

## Contribution

The paper identifies specific brain regions involved in encoding associations between negative emotional states and alcohol-related stimuli.

## Key findings

- Engrams in the PVT, CeA, and DS encode associations between dysphoric states and environmental contexts.
- These engrams may drive compulsive alcohol seeking and relapse vulnerability in alcohol-dependent rats.
- The study highlights a neural mechanism linking negative hedonic states to maladaptive behavior.

## Abstract

Engrams are neuronal alterations that encode associations between environmental contexts and subjectively rewarding or aversive experiences within sparsely activated neuronal assemblies that regulate behavioral responses. How positive- or negative-hedonic states are represented in brain neurocircuits is a fundamental question relevant for understanding the processing of emotionally meaningful stimuli that drive appropriate or maladaptive behavior, respectively. It is well-known that animals avoid noxious stimuli and experiences. Little is known, however, how the conditioning of environmental or contextual stimuli to behavior that leads to amelioration of dysphoric states establishes powerful associations leading to compulsive maladaptive behavior. Here we have studied engrams that encode the conditioned effects of alcohol-related stimuli associated with the reversal of the dysphoric withdrawal state in alcohol dependent rats and document the recruitment of engrams in the paraventricular nucleus of the thalamus (PVT), the central nucleus of the amygdala (CeA), and the Dorsal Striatum (DS). The findings suggest that the encoding of associations between reversal of negative hedonic states and environmental contexts in these engrams may serve as a neural mechanism for compulsive alcohol seeking and vulnerability to relapse associated with dysregulation of reward to a pathological allostatic level.