Effect of electro-acupuncture on motor dysfunction in middle cerebral artery occlusion/reperfusion rats though cortex-striatum somatostatin neural circuit

Ischemic stroke caused motor dysfunction results poses substantial health burdens and socioeconomic challenges. Electro-acupuncture (EA) at the acupoints of Quchi (LI11) and Zusanli (ST36) has shown positive efficacy in motor dysfunction after stroke. Considering the reported functions of the GABAergic system in locomotion, the present study aims to investigate the detailed mechanism of EA effects on motor regulation, focusing on the neural histological and chemical changes in the GABAergic system. Results demonstrated that EA at LI11 and ST36 improved the modified neurological severity score (mNNS) score and motor function of MCAO/R rats. EA at LI11 and ST36 also prompted γ-aminobutyric acid-ergic (GABAergic) system by the expression of GABA related receptors and GABA interneurons. Here, We have identified long-range projecting GABAergic interneurons, which can be classified into different subtypes based on the molecular markers they express: Parvalbumin (PV+), Somatostatin (SST+), and Vasoactive Intestinal Peptide (VIP+). Additionally, optogenetic stimulation of this projecting neurons can improve the motor dysfunction of MCAO/R rats. Notably, cortex M1-striatum (CS)-SST neural circuit which showed an indescribable role in locomotion improvement under EA intervention. The downregulation of the type II dopamine receptor in medium-sized spiny neurons (DR2-MSNs) and the upregulation of Synaptophysin (SYN) and Postsynaptic Density-95 (PSD95) suggest that MSNs and synaptic plasticity might be the downstream mechanisms of EA treatment at LI11 and ST36. To conclude, EA at LI11 and ST36 can promote synaptic plasticity and improve motor function by targeting and regulate downregulated DR2-MSNs neurons through the CS-SST neural circuit.