Tsc1 deletion in Purkinje neurons disrupts the axon initial segment, impairing excitability and cerebellar function.

ABSTRACT: Loss-of-function mutations in tuberous sclerosis 1 (TSC1) are prevalent monogenic causes of autism spectrum disorder (ASD). Selective deletion of Tsc1 from mouse cerebellar Purkinje neurons has been shown to cause several ASD-linked behavioral impairments, which are linked to reduced Purkinje neuron repetitive firing rates. We used electrophysiology methods to investigate why Purkinje neuron-specific Tsc1 deletion (Tsc1^mut/mut) impairs Purkinje neuron firing. These studies revealed a depolarized shift in action potential threshold voltage, an effect that we link to reduced expression of the fast-transient voltage-gated sodium (Nav) current in Tsc1^mut/mut Purkinje neurons. The reduced Nav currents in these cells was associated with diminished secondary immunofluorescen

SUBMITTER: Brown SP 

PROVIDER: S-EPMC11997981 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature