Paraventricular Thalamus Neuronal Ensembles Encode Early-life Adversity and Mediate the Consequent Sex-dependent Disruptions of Adult Reward Behaviors

Abstract

AbstractEarly-life adversity increases risk for mental illnesses including depression and substance use disorders, disorders characterized by dysregulated reward behaviors. However, the mechanisms by which transient ELA enduringly impacts reward circuitries are not well understood. In mice, ELA leads to anhedonia-like behaviors in males and augmented motivation for palatable food and sex-reward cues in females. Here, the use of genetic tagging demonstrated robust, preferential, and sex-specific activation of the paraventricular nucleus of the thalamus (PVT) during ELA and a potentiated reactivation of these PVT neurons during a reward task in adult ELA mice. Chemogenetic manipulation of specific ensembles of PVT neurons engaged during ELA identified a role for the posterior PVT in ELA-induced aberrantly augmented reward behaviors in females. In contrast, anterior PVT neurons activated during ELA were required for the anhedonia-like behaviors in males. Thus, the PVT encodes adverse experiences early-in life, prior to the emergence of the hippocampal memory system, and contributes critically to the lasting, sex-modulated impacts of ELA on reward behaviors.