Modulation of Input-Output Balance by the Axon Initial Segment

Brain stimulation therapies involve activating or touching the brain directly with electricity, magnets, or implants to treat different brain traumas or disorders. However, most studies do not take in account the relation between these therapies and the corresponding morphological and molecular changes in neurons. These changes depend on the external stimulation frequency and intensity, and are different in each subset of neurons, meaning an absence of neuronal excitability control. In this sense, the Axon Initial Segment is place of action potential initiation. This axonal domain has the property of changing its density of voltage gated ion channels, its position and length in response to different levels of stimuli. In this presentation we will review the molecular mechanisms that control neuronal excitability at the Axon Initial Segment and the different types of AIS plasticity that may explain the success or failure of therapies involving electrical stimulation of neurons.