Regulation of Axon Initial Segment Diameter by COUP-TFI Fine-tunes Action Potential Generation

The axon initial segment(AIS)is a specialized structure that controls neuronal excitability via action potential(AP)generation.Currently,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(chicken ovalbumin upstream promotor-transcription factor 1)is an essential regulator of AIS diameter in both developing and adult mouse neocortex.Either embryonic or adult ablation of COUP-TFI results in reduced AIS diameter and impaired AP generation.Although COUP-TFI ablations in sparse single neurons and in populations of neurons have similar impacts on AIS diameter and AP generation,they strengthen and weaken,respectively,the receiving spontaneous network in mutant neurons.In contrast,overexpression of COUP-TFI in sparse single neurons increases the AIS diameter and facilitates AP generation,but decreases the receiving spontaneous network.Our findings demonstrate that COUP-TFI is indispensable for both the expansion and maintenance of AIS diameter and that AIS diameter fine-tunes action potential generation and synaptic inputs in mammalian cortical neurons.

Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells

Spinal motor neurons deficiency results in a series of devastating disorders such as amyotrophic lateral sclerosis(ALS),spinal muscular atrophy(SMA)and spinal cord injury(SCI).These disorders are currently incurable,while human pluripotent stem cells(hPSCs)-derived spinal motor neurons are promising but suffered from inappropriate regional identity and functional immaturity for the study and treatment of posterior spinal cord related injuries.In this study,we have established human spinal cord neural progenitor cells(hSCNPCs)via hPSCs differentiated neuromesodermal progenitors(NMPs)and demonstrated the hSCNPCs can be continuously expanded up to 40 passages.hSCNPCs can be rapidly differentiated into posterior spinal motor neurons with high efficiency.The functional maturity has been examined in detail.Moreover,a co-culture scheme which is compatible for both neural and muscular differentiation is developed to mimic the neuromuscular junction(NMJ)formation in vitro.Together,these studies highlight the potential avenues for generating clinically relevant spinal motor neurons and modeling neuromuscular diseases through our defined hSCNPCs.

Giant infrared bulk photovoltaic effect in tellurene for broad-spectrum neuromodulation

Given the surpassing of the Shockley-Quiesser efficiency limit in conventional p-n junction photovoltaic effect,bulk photovoltaic effect(BPVE)has garnered significant research interest.However,the BPVE primarily focuses on a narrow wavelength range,limiting its potential applications.Here we report a giant infrared bulk photovoltaic effect in tellurene(Te)for broad-spectrum neuromodulation.The generated photocurrent in uniformly illuminated Te excludes other photoelectric effects and is attributed to the BPVE.The bulk photovoltaic wavelength in Te spans a wide range from the ultraviolet(390 nm)to the mid-infrared(3.8μm).Moreover,the photocurrent density of 70.4 A cm^(−2) under infrared light simulation outperforms that in previous ultraviolet and visible semiconductors as well as infrared semimetals.Te attached to the dendrites or somata of the cortical neurons successfully elicit action potentials under broad-spectrum light irradiation.This work lays the foundation for the further development of infrared BPVE in narrow bandgap materials.