Dissecting the stress circuits of the paraventricular nucleus of the thalamus

National Institute Of Mental Health

Investigators

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Abstract

During the past year, our laboratory advanced its goal of understanding how thalamic circuits integrate internal states with external cues to guide behavior through several key publications. In one study, Macdonald et al. (2025, bioRxiv), we identified a synaptic mechanism by which projections from the PVT to the nucleus accumbens assign motivational value to action-derived safety. This work showed that thalamostriatal plasticity at PVT→CIN synapses stabilizes safety as an internally constructed goal, revealing how the thalamus supports value learning independently of action learning. In a complementary line of work, Yurgel, Gao et al. (2025, Science Advances), in collaboration with the Hattar group, uncovered an stress-sensitive circuit whereby the anterior PVT signals to the suprachiasmatic nucleus to reprogram circadian rhythms. Unlike light, which can either advance or delay circadian phase, stressors consistently induced phase delays, highlighting a distinct thalamic pathway through which aversive experiences reshape temporal organization of behavior. Finally, as part of a collaborative effort led by the McMahon and Marenco groups, Schulmann et al. (2024, bioRxiv) identified a conserved cell-type gradient across the human mediodorsal thalamus and PVT. Our contributions to this study helped establish a transcriptomic framework for the human midline thalamus and provided a foundation for cross-species comparisons linking molecular architecture to cognition and psychopathology. Collectively, these studies reinforce the view that the PVT is a central node in internal goal prioritization, whether by encoding the motivational value of safety, transmitting stress signals to circadian clocks, or embodying conserved organizational principles in the human thalamus. By situating the PVT at the intersection of internal state representation and adaptive behavior, this work advances a broader conceptualization of the thalamus as a computational hub for internal-state inference with implications for psychiatric disease.