The encoding of interoceptive-based predictions by the paraventricular nucleus of the thalamus D2R+ neurons

ABSTRACT Understanding how the brain integrates internal physiological states with external sensory cues to guide behavior is a fundamental question in neuroscience. This process relies on interoceptive predictions, which are internal models that anticipate changes in the body’s physiological state based on sensory inputs and prior experiences. Despite recent advances in identifying the neural substrates of interoceptive predictions, the precise neuronal circuits involved remain elusive. In our study, we demonstrate that Dopamine 2 Receptor (D2R+) expressing neurons in the paraventricular nucleus of the thalamus (PVT) play key roles in interoception and interoceptive predictions. Specifically, these neurons are engaged in behaviors leading to physiologically relevant outcomes, with their activity highly dependent on the interoceptive state of the mice and the expected outcome. Furthermore, we show that chronic inhibition of PVT D2R+ neurons impairs the long-term performance of interoceptive-guided motivated behavior. Collectively, our findings provide insights into the role of PVT D2R+ neurons in learning and updating state-dependent predictions by integrating past experiences with current physiological conditions to optimize goal-directed behavior.