Prime editing and base editing in mouse models and human cells effectively correct mutations in a gene that causes a childhood neurodevelopmental disorder called alternating hemiplegia of childhood. I...

The worldwide legalization of medicinal cannabis has led to an increased use of products made by commercial operators. These products often contain minor cannabinoids such as cannabinol (CBN) which a...

Dravet syndrome is a severe, intractable epilepsy in which 80 % of patients have a de novo mutation in the gene SCN1A. We recently reported that a hig…

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Pathogenic variants in ATP1A3 encoding the neuronal Na/K-ATPase cause a spectrum of neurodevelopmental disorders including alternating hemiplegia of c…

At the simplest level, neurons are structured to integrate synaptic input and perform computational transforms on that input, converting it into an action potential (AP) code. This process-converting synaptic input into AP output-typically occurs in a specialized region of axon termed the axon initial segment (AIS). The AIS, as its name implies, is often contained to the first section of axon abutted to the soma and is home to a dizzying array of ion channels, attendant scaffolding proteins, intracellular organelles, extracellular proteins, and, in some cases, synapses. The AIS serves multiple roles as the final arbiter for determining if inputs are sufficient to evoke APs, as a gatekeeper that physically separates the somatodendritic domain from the axon proper, and as a regulator of overall neuronal excitability, dynamically tuning its size to best suit the needs of parent neurons. These complex roles have received considerable attention from experimentalists and theoreticians alike. Here, we review recent advances in our understanding of the AIS and its role in neuronal integration and polarity in health and disease.

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