期刊
JOURNAL OF NEUROPHYSIOLOGY
卷 129, 期 4, 页码 937-947出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00029.2022
关键词
auditory cortex; auditory processing; autism; patch -clamp; development
Disruptions in the CNTNAP2 gene are associated with language impairments and symptoms of autism spectrum disorder (ASD). Knocking out this gene in rodents leads to ASD-like symptoms, including auditory processing deficits. This study found that CNTNAP2 is crucial for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex.
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 audi-tory 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 spontane-ous synaptic input. Intrinsic cell properties such as action potential half-widths, rheobase, and action-potential firing frequencies were dif-ferent 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 syn-aptic 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据