The IC-SNc neural circuit mediates prepulse inhibition deficits in MPTP-induced Parkinson's disease male mice.

Clinical studies suggest that Parkinson's disease (PD) patients exhibit sensorimotor gating impairment, as manifested by deficits in prepulse inhibition (PPI). However, the underlying neural mechanisms remain elusive. Using the MPTP-induced PD mouse model, we demonstrated that substantia nigra pars compacta dopaminergic (SNcDA) neurons damage directly induces a reduction in PPI, whereas activation of these neurons reverses MPTP-induced PPI deficits. Viral tracing revealed an inferior colliculus (IC)-SNcDA circuit, whose bidirectional modulation mimics or rescues PPI impairment in MPTP male mice. Furthermore, the SNcDA neurons outputs from pedunculopontine nucleus (PPN) to reticulotegmental nucleus (RtTg) also involved in regulating MPTP-induced PPI deficits. This study identifies SNcDA neurons inputs and outputs as key modulators of PPI deficits in MPTP-treated male mice, thereby providing the circuit-level mechanism of sensorimotor gating impairment in early-stage PD.