Transcranial magneto-acoustic stimulation improves corticostriatal transmission in direct medium spiny neurons and rescues neuroplasticity of Parkinson’s disease model mice

Transcranial magneto-acoustic stimulation (TMAS) is a noninvasive neuromodulation technique that has demonstrated benefits for neuroplasticity in Parkinson's disease (PD), yet its underlying mechanisms remain inadequately understood. This study aimed to investigate how TMAS affects dysfunction and synaptic-plasticity impairments in the corticostriatal pathway in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. The results indicated that TMAS was associated with reduced presynaptic glutamate release and with improved N-methyl-D-aspartate receptor (NMDAR)-mediated responses. It also enhanced D1 dopamine receptor-dependent basal synaptic transmission and partially restored bidirectional corticostriatal synaptic plasticity. Furthermore, TMAS tended to normalize the distribution of spine subtypes, improve motor deficits, reduce dopaminergic neuron loss, and decrease aberrant α-synuclein expression. Transcriptomic and enrichment analyses further suggested a coordinated modulation of gene programs related to synaptic organization, ion homeostasis, and immune responses. These findings support TMAS as a promising noninvasive neuromodulation approach in the MPTP mouse model. TMAS attenuated excessive glutamatergic transmission and improved corticostriatal synaptic plasticity, providing a testable mechanistic framework for future studies.