Activation of Cortical Somatostatin Interneurons Rescues Synapse Loss and Motor Deficits after Acute MPTP Infusion

Adult dendritic spines present structural and functional plasticity, which forms the basis of learning and memory. To provide in vivo evidence of spine plasticity under neurotoxicity, we generated an acute motor deficit model by single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into adult mice. Acute MPTP infusion impairs motor learnings across test paradigms. In vivo two-photon imaging further revealed MPTP-induced prominent dendritic spine loss and substantially increased calcium spikes in apical tufts of layer 5 pyramidal neurons in the motor cortex. MPTP infusion also decreased the activity of somatostatin (SST)-expressing inhibitory interneurons. Further chemogenetic re-activation of SST interneurons reversed MPTP-induced hyperactivation of dendrites, rescued spine loss, and enhanced motor learning. Taken together, our study reports MPTP-induced structural and functional deficits of dendritic spines and suggests the potency of modulating local inhibitory transmission to relieve neurological disorders.