AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Embryonic ablation of COUP-TFI prevented expansion of AIS diameter that occurs during postnatal development in layer II/III pyramidal cells of the motor cortex, thereby leading to impaired action potential generation. Inactivation of COUP-TFI in adult neurons led to reduced AIS diameter and impaired action potential generation. In contrast to different developmental stages, single-cell ablation and global ablation produced opposite effects on spontaneous network in COUP-TFI-deficient neurons. Further, mice exhibited less anxiety-like behaviors after postnatal inactivation of COUP-TFI by tamoxifen. Our results demonstrate that COUP-TFI is indispensable for both expansion and maintenance of AIS diameter and that a change in AIS diameter fine-tunes synaptic inputs.
bioRxiv Subject Collection: Neuroscience