Coupling Compartmental Models to Live Neurons to Investigate Action Potential Mechanisms

Abstract

In mammalian central neurons, action potentials are initiated in the axonal initial segment (AIS) by Nav1.2 and Nav1.6 channels, and shaped and terminated by other voltage-gated ion channels. From the AIS, the AP travels down the axon towards the presynaptic site, but also back-propagates towards the soma. The role of axonal sodium channels in AP initiation and propagation is still incompletely understood, mostly because it is difficult to record from these channels at the AIS. Instead, most experimental evidence of axonal activity is obtained indirectly, from electrical recordings at the soma. To better understand these mechanisms, we developed a real-time computational procedure where a compartmental model of the axon is coupled to a live neuron using dynamic clamp. The properties of this computational model (e.g., spatial distribution and kinetics of ion channels) are varied until the firing activity of the hybrid construct (neuron + axon compartmental model) best matches the normal activity of the neuron.