Neural and molecular investigation into the paraventricular thalamus for chronic restraint stress induced depressive-like behaviors

Abstract

IntroductionDisturbance of neural circuits and chronic stress contribute to depression onset. Given the crucial role of paraventricular nucleus of thalamus (PVT) in emotional behaviors, however, the specific neural and molecular mechanism of PVT in depression still unclear. ObjectiveOur study aim to explore the neural and molecular mechanism of PVT in depression. MethodsIn the present study, we utilize behavioral tests,chemogenetics, RNA-sequence, molecular profiling and pharmacological approaches to investigate the role of PVT in depression. ResultsWe observed that CamkIIα neurons in PVT were inactivated by chronic restraint stress (CRS) with reduced c-Fos positive neurons. Activation of PVTCamkIIα neurons displayed antidepressant-like effect in both naive and CRS mice, whereas inhibition or ablation of these neurons is sufficient to trigger depressive-like behaviors. Moreover, we found that activating PVT → Nucleus accumbens (NAc) circuit attenuated depressive-like behaviors induced by CRS, while inhibiting this circuit directly caused behavioral deficits in mice. Intriguingly, artificially enhancing PVT → Central amygdala (CeA) pathway failed to alleviate depressive-like behaviors. Importantly, increased expression of neuropeptide Y (NPY) and depressive-like behaviors induced by CRS could be ameliorated via antidepressant treatment, manipulation of PVTCamkIIα neurons (or PVT → NAc circuit) and NPY inhibitor. ConclusionTaken together, our study uncovered that PVT regulated depressive-like behaviors via PVT → NAc circuit together with NPY, thus shedding light on potential target for preventing depression and promoting clinical translation.