Abstract
The anatomical properties of the axon initial segment (AIS) are tailored in certain types of CNS neurons to help optimize different aspects of neuronal function. Here, we questioned whether the AISs of retinal ganglion cells (RGC) were similarly customized, and if so, whether they supported specific RGC functions. To explore this, we measured the AIS properties in alpha sustained RGCs (α S RGCs) of mouse; α S RGCs sizes vary systematically along the nasal temporal axis of the retina, making these cells an attractive population with which to study potential correlations between AIS properties and cell size. Measurements of AIS length as well as distance from the soma revealed that both were scaled to cell size, i.e., cells with large dendritic fields had long AISs that were relatively far from the soma. Within the AIS, the percentage of Nav1.6 voltage-gated sodium channels remained highly consistent, regardless of cell size or other AIS properties. Although ON RGCs were slightly larger than OFF cells at any given location of the retina, the level of scaling and relative distribution of voltage-gated sodium channels were highly similar. Computational modeling revealed that AIS scaling influenced spiking thresholds, spike rate as well as the kinetics of individual action potentials, Interestingly, the effect of individual features of the AIS varied for different neuronal functions, e.g., AIS length had a larger effect on the efficacy by which the AIS initiated spike triggered the somatic spike than it did on repetitive spiking. The polarity of the effect varied for different properties, i.e., increases to soma size increased spike threshold while increases to AIS length decreased threshold. Thus, variations in the relative level of scaling for individual components could fine tune threshold or other neuronal functions. Light responses were highly consistent across the full range of cell sizes suggesting that scaling may post-synaptically shape response stability, e.g., in addition to several well-known pre-synaptic contributors.
Highlights
The axon initial segment (AIS) is a specialized portion of the proximal axon that mediates the initiation and propagation of action potentials in CNS neurons
Our findings that show that at any given retinal eccentricity ON-α S retinal ganglion cells (RGCs) are slightly larger than OFF-α S RGCs (Supplementary Figure S2), including the fact that the AIS is longer and more distant from the soma in ON cells (Figure 2B), coupled with previous work that found that increases to both AIS length and distance reduce activation threshold in response to electrical stimulation (Jeng et al, 2011), suggests that at any given location ON cells have a slightly lower threshold than do OFF cells
PW performed the electrophysiology experiments and computational modeling
Summary
The axon initial segment (AIS) is a specialized portion of the proximal axon that mediates the initiation and propagation of action potentials in CNS neurons. In a previous study in rat retinal ganglion cells (RGCs) (Van Wart et al, 2007) the Nav1.6 portion was reported to comprise ∼2/3 of the total AIS length details were not provided as to whether the ratio was for a single cell type or an average across the population of all RGCs tested. The alpha Sustained (α S) RGCs of the mouse retina is a attractive population with which to study AIS structure and function because the size of these cells varies systematically across the retina (Bleckert et al, 2014), i.e., the relationship between AIS properties and cell size can be directly evaluated. Scaling may help to stabilize responses across the population
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