Abstract
Electroacupuncture (EA) has been shown to suppress premature ventricular complexes (PVCs) following myocardial infarction (MI) in humans. However, the specific neural circuitry and causal mechanisms underlying this effect remain unclear. Here, we reveal a previously unrecognized connection from the primary motor cortex (M1) to the nucleus rostral ventrolateral medulla (RVLM) circuitry via the layer 5 of the primary motor cortex (M1L5)-zona incerta (ZI) pathway, which selectively suppresses PVCs in post-MI mice. Utilizing viral tracing, fiber photometry recordings, and optogenetic stimulation, we demonstrate that EA inhibits glutamatergic projections from M1L5 to ZI, leading to the activation of local GABAergic neurons and subsequent inhibition of RVLM (M1L5-ZI-RVLM). Furthermore, optogenetic or chemogenetic inhibition of the M1L5-ZI-RVLM circuit replicates the anti-PVC effects observed with EA in MI mice. Artificial activation of M1L5-projecting ZI neurons reverses the suppressive effects of EA on PVCs in MI mice. Overall, our findings highlight the M1L5-ZI-RVLM circuit as a crucial mediator of EA-induced suppression of PVCs following myocardial infarction. Additionally, this newly identified corticothalamic circuit may represent a promising target for mitigating PVCs post-myocardial infarction.