Electroacupuncture Ameliorates Learning and Memory Deficits in Vascular Cognitive Impairment Rats Through Activation of the Supramammillary Nucleus-Dentate Gyrus Circuit.

AIMS: This study aimed to elucidate the potential mechanism, especially neural circuit mechanisms, through which electroacupuncture (EA) mitigates cognitive decline in a rat model of vascular cognitive impairment (VCI).

METHODS

Using a rat two-vessel occlusion (2VO) model, we assessed the therapeutic impact of EA on spatial and non-spatial memory. We integrated in vivo fiber photometry and immunofluorescence to monitor neuronal activities in the dentate gyrus (DG) and supramammillary nucleus (SuM), while Golgi staining was employed to evaluate hippocampal synaptic plasticity. Viral tracing and chemogenetic manipulations were utilized to characterize the functional necessity of the SuMGlu-DG circuit.

RESULTS

EA at ST36 significantly restored learning and memory function. This functional recovery was accompanied by improved synaptic plasticity and heightened neuronal activity in the DG. Fiber photometry revealed that EA specifically activated glutamatergic neurons in the SuM, a key upstream regulator of the DG. Notably, targeted chemogenetic inhibition of the SuMGlu-DG circuit abolished the cognitive improvements typically induced by EA.

CONCLUSION

Our findings demonstrate that EA ameliorates learning and memory deficits in VCI through regulating the SuMGlu-DG circuit.