The glutamatergic NTS-PAG/PVN pathway underlies myocardial injury and anxiety-like behavior induced by myocardial ischemia-reperfusion.

For patients with myocardial ischemia-reperfusion injury (MIRI), cardiac dysfunction accompanied by anxiety is an extremely common comorbidity. Although the association between these two conditions has received some attention, the underlying neural mechanisms remain unclear. Here, we functionally characterized two distinct glutamatergic (Glu) neural pathways in the nucleus tractus solitarius (NTS) of male mice, a pathway from the NTS to the periaqueductal gray (PAG) that mediates anxiety-like behaviors in MIRI mice, and a pathway from the NTS to the paraventricular nucleus of the hypothalamus (PVN) that influences cardiac dysfunction following MIRI. Chemogenetic inhibition of these two pathways simultaneously ameliorated both the anxiety-like behaviors and cardiac dysfunction in MIRI mice. Thus, our study reveals that the distinct circuits NTSGlu-PAG and NTSGlu-PVN separately encode anxiety-like emotions and cardiac dysfunction after myocardial ischemia-reperfusion, thereby providing insights at the neural circuit level for improving both cardiac dysfunction and anxiety-like emotions following MIRI.