Persistently increased post-stress activity of paraventicular thalamic neurons is essential for the emergence of stress-induced alterations in behaviour
PLoS Biol 23(1): e3002962 (2025)
DOI: 10.1371/journal.pbio.3002962
Jász A1,2, Biró L1,3, Buday Z1,2,3, Király B1,3,4, Szalárdy O5, Horváth K6, Komlósi G1,3, Bódizs R5, Kovács K6, Diana MA7, Hangya B1,3, Acsády L1,3
1 Lendület Laboratory of Thalamus Research, HUN-REN Institute of Experimental Medicine, Budapest, Hungary
2 Neurosciences PhD School, Semmelweis University, Budapest, Hungary
3 Institute of Experimental Medicine, Budapest, Hungary
4 Department of Biological Physics, Institute of Physics, Eötvös Loránd University, Budapest, Hungary
5 Psychophysiology and Chronobiology Research Group, Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary
6 Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary
7 Université Paris Cité, CNRS, Saint-Pères Paris Institute for the Neurosciences, Paris, France
ABSTRACT
A single exposure to a stressful event can result in enduring changes in behaviour. Long-term modifications in neuronal networks induced by stress are well explored but the initial steps leading to these alterations remain incompletely understood. In this study, we found that acute stress exposure triggers an immediate increase in the firing activity of calretinin-positive neurons in the paraventricular thalamic nucleus (PVT/CR+) that persists for several days in mice. This increase in activity had a causal role in stress-induced changes in spontaneous behaviour. Attenuating PVT/CR+ neuronal activity for only 1 h after the stress event rescued both the protracted increase in PVT/CR+ firing rate and the stress-induced behavioural alterations. Activation of the key forebrain targets (basolateral amygdala, prelimbic cortex, and nucleus accumbens) that mediate defensive behaviour has also been reduced by this post-stress inhibition. Reduction of PVT/CR+ cell activity 5 days later remained still effective in ameliorating stress-induced changes in spontaneous behaviour. The results demonstrate a critical role of the prolonged, post-stress changes in firing activity of PVT/CR+ neurons in shaping the behavioural changes associated with stress. Our data proposes a therapeutic window for intervention in acute stress-related disorders, offering potential avenues for targeted treatment strategies.