Developmental changes in electrophysiological properties of auditory cortical neurons in the Cntnap2 knockout rat

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2 rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2 littermates at three postnatal age ranges (P8-12, P18-21, and P70-90). Consistent changes across age were seen in all measures of intrinsic membrane properties and spontaneous synaptic input. Intrinsic cell properties such as action potential half-widths, rheobase, and action-potential firing frequencies were different between wildtype and Cntnap2 rats predominantly during the juvenile stage (P18-21), whereas adult Cntnap2 rats showed higher frequencies of spontaneous and mini postsynaptic currents (sPSCs; mPSCs), with lower sPSC amplitudes. These results indicate that intrinsic cell properties are altered in Cntnap2 rats during the juvenile age, leading to a hyperexcitable phenotype during this stage of synaptic remodeling and refinement. Although intrinsic properties eventually normalize by reaching adulthood, changes in synaptic input, potentially caused by the differences in intrinsic membrane properties, seem to manifest in the adult age and are presumably responsible for the hyperreactive behavioral phenotype. In conjunction with a previous study, the present results also indicate a large influence of breeding scheme, i.e., pre- or postnatal environment, on the impact of Cntnap2 on cellular physiology.NEW & NOTEWORTHY This study shows that neurons in the auditory cortex of Cntnap2 knockout rats are hyperexcitable only during the juvenile age, whereas resulting changes in synaptic input persist in the adult. In conjunction with a previous study, the present results indicate that it is not the genes alone, but also the influence of pre- and postnatal environment, that shape neuronal function, highlighting the importance of early intervention in neurodevelopmental disorders.