Plasticity of GABAA receptor diffusion dynamics at the axon initial segment

Abstract

The axon initial segment (AIS), a site of action potential initiation, undergoes activity-dependent homeostatic repositioning to fine-tune neuronal activity. However, little is known about the behavior of GABAA receptors (GABAARs) at synapses made onto the axon and especially the AIS. Here, we study the clustering and lateral diffusion of GABAA Rs in the AIS under baseline conditions, and find that GABAA R lateral mobility is lower in the AIS than dendrites. We find differences in axonal clustering and lateral mobility between GABAA Rs containing the α1 or α2 subunits, which are known to localize differentially to the AIS. Interestingly, we find that chronic activity driving AIS repositioning does not alter GABAergic synapse location along the axon, but decreases GABAA R cluster size at the AIS. Moreover, in response to chronic depolarization, GABAA R diffusion is strikingly increased in the AIS, and not in dendrites, and this is coupled with a decrease in synaptic residency time of GABAA Rs at the AIS. We also demonstrate that activation of L-type voltage-gated calcium channels is important for regulating GABAA R lateral mobility at the AIS during chronic depolarization. Modulation of GABAA R diffusion dynamics at the AIS in response to prolonged activity may be a novel mechanism for regulating GABAergic control of information processing. © 2014 Muir and Kittler.