# Paraventricular Nucleus of the Thalamus Neurons That Project to the Nucleus Accumbens Show Enhanced c‐Fos Expression During Early‐Stage Cue‐Reward Associative Learning in Male Rats

## TL;DR

This study finds that specific brain neurons become more active early in learning how cues relate to rewards in rats.

## Contribution

The study identifies that PVT neurons projecting to the nucleus accumbens show enhanced c-Fos expression during early cue-reward learning.

## Key findings

- PVT neurons projecting to the nucleus accumbens show increased c-Fos expression after first exposure to cue-reward associations.
- Control groups with random cue-reward intervals showed significantly lower c-Fos activation in these neurons.
- Early c-Fos activation in these neurons may modulate plasticity in the nucleus accumbens during associative learning.

## Abstract

The paraventricular nucleus of the thalamus (PVT) is a central node in brain networks controlling motivated behaviors. It processes inputs from cerebral cortex, brainstem, and hypothalamus and has efferents that project to a wide range of structures, including the nucleus accumbens (nAcc). It is known that PVT neurons projecting to the nAcc show c‐Fos activation in response to reward‐related cues, in well‐trained animals. We previously found that c‐Fos expression is also increased early in the conditioning process, during the first session of learning a new cue‐reward association in rats, but neurons with projections to nAcc were not identified in that study. Here, we tested the hypothesis that nAcc‐projecting PVT neurons would show this enhanced c‐Fos expression following first exposure to the association of a visual cue with a subsequent food reward. Male rats were stereotaxically injected in the nAcc with a retrogradely transported adeno‐associated virus construct leading to green fluorescent protein (GFP) expression in cell bodies of afferents from PVT. Following a single session of cue‐reward training, processing of the brains with dual immunohistochemistry for c‐Fos and GFP showed significantly higher density of double labelled neurons in the conditioned group, compared to controls in which the same number of cues and rewards were delivered at random intervals with respect to each other. Such activation of immediate early gene expression in PVT to nAcc projecting neurons very early in paired associative reward learning may have a role in modulating plasticity in the nAcc.

Retrogradely transported AAV was injected bilaterally into nAcc, leading to GFP expression in PVT projection neurons. In the control group, a visual cue and food rewards occurred at random intervals. In the S→R group, the cue preceded the reward by a fixed interval. After one task session, double immunohistochemistry for GFP and c‐Fos expression revealed significantly increased density of c‐Fos positive nuclei in PVT projection neurons in the S→R group compared to controls. Created with BioRender.com.