Paraventricular thalamic neurons respond to vagus nerve activation and modulate anxious behavior

Abstract

Interoceptive signals reflecting internal bodily states influence emotional processing. The paraventricular thalamus (PVT) constitutes a key node within the interoceptive network, monitoring circulating humoral factors in the ventricles, and is thus considered to link interoceptive signals to emotion-related behaviors. Here, we demonstrate that the vagus nerve (VN), a principal afferent pathway for interoceptive signaling, also affects PVT neuronal activity in mice. Left vagus nerve stimulation (VNS) induced pronounced c-Fos expression in PVT neurons and elicited transient increases and decreases in neuronal spike rates across all PVT subregions. These VNS-responsive neuronal populations were distinct from those exhibiting transient-to-sustained delayed responses following lipopolysaccharide injection after vagotomy, which selectively activates VN-independent pathways, including humoral factors. VNS-responsive PVT neurons projected to limbic structures and modulated anxiety-like behavior. Taken together, these findings demonstrate that PVT neuronal populations integrate and relay interoceptive signals across multiple pathways and timescales, thereby playing a pivotal role in linking vagus nerve-related bodily states to emotional responses.