Action Potential Generation at an Axon Initial Segment-Like Process in the Axonless Retinal AII Amacrine Cell

In axon-bearing neurons, action potentials conventionally initiate at the axon initial segment (AIS) and are important for neuron excitability and cell-to-cell communication. However in axonless neurons, spike origin has remained unclear. Here we report in the axonless, spiking AII amacrine cell of the mouse retina a dendritic process sharing organizational and functional similarities with the AIS. This process was revealed through viral-mediated expression of channelrhodopsin-2-GFP with the AIS-targeting motif of sodium channels (NavII-III). The AII processes showed clustering of voltage-gated Na+ channel 1.1 (Na(v)1.1) as well as AIS markers ankyrin-G and neurofascin. Furthermore, NavII-III targeting disrupted Na(v)1.1 clustering in the AII process, which drastically decreased Na+ current and abolished the ability of the AII amacrine cell to generate spiking. Our findings indicate that, despite lacking an axon, spiking in the axonless neuron can originate at a specialized AIS-like process.