UCSF

The axon initial segment is a specialized region of most neurons where action potentials are initiated. The function of this compartment is derived from its dense collection of ion channels and scaffolding proteins, ranging from voltage-gated sodium channels and the ankyrin proteins that tether them to GABA receptors and the calcium stores that show tight colocalization with voltage-gated potassium channels. While careful work has illuminated how structure supports function in this complex compartment, several mysteries remain: (1) how are calcium channels organized at the axon initial segment, and how does this organization elucidate their function? and (2) how do chandelier cells, the GABAergic interneurons that exclusively and selectively target the axon initial segment, affect the function and output of their pyramidal neuron targets?Here, using whole-cell patch-clamp electrophysiology, calcium imaging, and two-photon laser-scanning microscopy, I show that a mixture of calcium channels are found in the axon initial segment of layer 5 pyramidal neurons, where their differential organization hints at different functional roles. Additionally, I show that the complement of calcium channels present at the initial segment is a mixture of channels typically found in the dendrites or axon terminals exclusively. I go on to identify the mechanism by which chandelier cells inhibit pyramidal neuron output, despite a shift in the reversal potential of GABA that occurs in the middle of adolescent development that occurs only at the initial segment. These data support the idea that the axon initial segment is a specialized intermediate zone that incorporates properties of both somatodendritic and axonal regions.