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

Sarah Goethals,Romain Brette,Annabelle Réaux-Le Goazigo,Martijn C. Sierksma,Xavier Nicol

doi:10.1152/jn.00005.2021

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 retinal ganglion cells 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 covaries 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.NEW & NOTEWORTHY We measured the axial current produced at spike initiation by the axon initial segment of mouse retinal ganglion cells. We found that it is a large current, requiring high sodium channel conductance density, which covaries with cell capacitance so as to ensure a ∼30 mV depolarization. During sustained depolarization the current attenuated, but it broadened to preserve somatic depolarization. Thus, properties of the initial segment are adjusted to ensure backpropagation of the axonal action potential.

Highlights

In most vertebrate neurons, action potentials (APs) initiate in the axon initial segment (AIS), a highly organized structure near the soma (Bender & Trussell, 2012), propagate forward to the axon terminals and backward to the soma and dendrites (Debanne et al, 2011)
Work on vertebrate motoneurons showed that APs recorded in the soma typically consist of two components (Fatt, 1957; Coombs et al, 1957): an abrupt depolarization due to the axial current originating from the axon initial segment, followed by a regeneration of the AP at a higher potential, by the opening of somatic sodium channels
These two components are clearly distinguished in recordings of spontaneous APs of retinal ganglion cells (RGC)

Summary

Introduction

Action potentials (APs) initiate in the axon initial segment (AIS), a highly organized structure near the soma (Bender & Trussell, 2012), propagate forward to the axon terminals and backward to the soma and dendrites (Debanne et al, 2011). The fact that the AIS, a small structure, must produce a current able to charge a much larger piece of membrane (soma and proximal dendrites), suggests that conductance density is high, in agreement with immunochemical observations (Lorincz & Nusser, 2010). This has remained a somewhat contentious issue (Fleidervish et al, 2010) because direct patch-clamp measurements in the intact AIS indicate low conductance density (Colbert & Pan, 2002), which could be an artifact due to the anchoring of channels to the cytoskeleton (Kole et al, 2008). We examined the axial current at spike initiation, just below threshold, and with threshold adaptation, and compared these results to theoretical predictions

Results

Summary

Limitations

Ethical statement

A Taylor expansion gives:

Funding information