Small domain, large consequences: the axon initial segment as a key player in neuronal excitability

Abstract

Abstract The axon initial segment (AIS) is a crucial axonal domain for neuronal function – it allows neurons to generate action potentials, maintain their polarity or modulate their own excitability, thereby adapting to sudden and more long-term changes in network state. Although the AIS has been a well-described structure in neurons with work dating back to the 1960s, its fundamental role in neuronal function has only really been appreciated in the last decade. It is therefore no surprise that the AIS now also emerges as a hub for the onset of various pathophysiological conditions. In this review, we will focus on AIS development, function, and plasticity in the context of neuronal network activity and will highlight recent results that indicate a role for the AIS in the regulation and fine-tuning of input-output relations in single neurons.