The central role of hypothalamic circuits for anti-Parkinsonian effects of acupuncture

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in central nervous system disorders has remained elusive. In this study, using an established model of acupuncture treatment in Parkinson’s disease (PD) mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. Moreover, we identify two distinct neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, we elucidate their individual roles in mediating acupuncture-induced motor recovery and memory improvements following PD onset. Additionally, we demonstrate the underlying mechanisms of recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. In conclusion, we find these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture but also a potential cellular target for treating both motor and non-motor PD symptoms.