Work

Corticothalamic circuits drive voluntary physical exercise-mediated relief of surgery-induced negative emotions in mice

Year: 2026

Type: article

Abstract: Surgery-induced negative emotions (SINE), such as fear and anxiety, are common clinically and hinder postoperative recovery. Although physical exercise is known to modulate various affective disorders, the underlying mechanisms by which voluntary physical exercise alleviates SINE remain unclear. Here we show that emotional stress promotes conditioned defensive expression and anxiety-like behaviors following fear conditioning-paired exploratory laparotomy in mice, whereas preoperative voluntary running wheel exercise significantly decreases these SINE-related behaviors. In exercised male mice, emotional stress enhances the primary motor cortex glutamatergic neuronal (M1 Glu ) activity while suppressing posterior thalamic complex glutamatergic neurons (PO Glu ) via zona incerta GABAergic (ZI GABA ) inputs through a dominant inhibitory M1 Glu → ZI GABA →PO Glu circuit, thereby alleviating SINE behaviors. In addition, raised norepinephrine release in the M1 triggered by emotional stress drives the activity of this circuit to attenuate SINE behaviors. This study identifies a voluntary physical exercise-activated, NE-mediated corticothalamic circuit linking motor activity to emotional processing in male mice, expanding the application of physical exercise and pinpointing therapeutic targets for clinical treatments of post-surgical mental disorders.

Source: Communications Biology

DOI: 10.1038/s42003-026-11086-y