Aberrant axon initial segment is an indicator for task-independent neural activity in autism model mice

Abstract

Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in several communicative behaviors. Identification of biomarkers for ASD based on task-independent neural activity has been elusive. The axonal initial segment (AIS), located at the proximal part of the axon, is crucial for initiating action potentials (APs) and adaptable through activity-dependent AIS plasticity. In our study, we discovered decrease in AIS length in layer V pyramidal neurons (PyNs) of the prelimbic cortex (PrL) and increase in layer II/III PyNs in the somatosensory cortex of duplicated human 15q11-13 region (15q dup) ASD model mice. Electrophysiological studies using whole-cell patch-clamp recordings in the PrL revealed diminished ability to generate APs. We discovered lack of AIS plasticity in 15q dup mice under conditions of elevated potassium chloride. Retrograde tracing demonstrated that AIS shortening depends on the projection targets. These results indicate that activity-dependent aberrant AIS structures can serve as indicators of altered task-independent neural activity in ASD mouse models.