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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.

Axonal arbors in many neuronal networks are exuberant early during development and become refined by activity-dependent competitive mechanisms. Theoretical work proposed non-competitive interactions between co-active axons to co-stabilize their connections, but the demonstration of such interactions is lacking. Here, we provide experimental evidence that reducing cyclic AMP (cAMP) signaling in a subset of retinal ganglion cells favors the elimination of thalamic projections from neighboring neurons, pointing to a cAMP-dependent interaction that promotes axon stabilization., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The shape of the presynaptic action potential (AP) has a strong impact on neurotransmitter release. Because of the small size of most terminals in the central nervous system, little is known about the regulation of their AP shape during natural firing patterns in vivo. The calyx of Held is a giant axosomatic terminal in the auditory brainstem, whose biophysical properties have been well studied in slices. Here, we made whole-cell recordings from calyceal terminals in newborn rat pups. The calyx showed a characteristic burst firing pattern, which has previously been shown to originate from the cochlea. Surprisingly, even for frequencies over 200 Hz, the AP showed little or no depression. Current injections showed that the rate of rise of the AP depended strongly on its onset potential, and that the membrane potential after the AP ( V after ) was close to the value at which no depression would occur during high-frequency activity. Immunolabeling revealed that Na v 1.6 is already present at the calyx shortly after its formation, which was in line with the fast recovery from AP depression that we observed in slice recordings. Our findings thus indicate that fast recovery from depression and an inter-AP membrane potential that minimizes changes on the next AP in vivo, together enable high timing precision of the calyx of Held already shortly after its formation., Competing Interests: The authors declare no conflict of interest.