Electrical match between initial segment and somatodendritic compartment for action potential backpropagation in retinal ganglion cells

Abstract

The action potential of most vertebrate neurons initiates in the axon initial segment (AIS), and is then transmitted to the soma where it is regenerated by somatodendritic sodium channels. For successful transmission, the AIS must produce a strong axial current, so as to depolarize the soma to the threshold for somatic regeneration. Theoretically, this axial current depends on AIS geometry and Na+ conductance density. We measured the axial current of mouse RGCs using whole-cell recordings with post-hoc AIS labeling. We found that this current is large, implying high Na+ conductance density, and carries a charge that co-varies with capacitance so as to depolarize the soma by ∼30 mV. Additionally, we observed that the axial current attenuates strongly with depolarization, consistent with sodium channel inactivation, but temporally broadens so as to preserve the transmitted charge. Thus, the AIS appears to be organized so as to reliably backpropagate the axonal action potential.

Neural excitability increases with axonal resistance between soma and axon initial segment

“…In accordance with theory (12,18) and previous numerical studies (16), in the model, the rate of rise of the IS component is reduced when the threshold is hyperpolarized (Fig. 5F).…”

“…5F). In theory, this occurs because the backpropagated current is roughly ΔV =R a (by Ohm's law), where ΔV ≈ E Na − V threshold is the voltage gradient between the soma and AIS (12,18). We verified that this relation was also found in the experimental data.…”

“…Theoretical work predicts that the backpropagated current corresponding to the initial segment (IS) component varies inversely with R a (12,18). Thus, during pinching, the current may not be sufficient to trigger a full spike (19).…”