Axon Initial Segment Kv1 Channels Control Axonal Action Potential Waveform and Synaptic Efficacy

Abstract

Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

Effects of Axonal Topology on the Somatic Modulation of Synaptic Outputs

“…In neocortical pyramidal cells and dentate granule cells in acute slice preparations, it has been shown that axonal depolarization by somatic depolarization is reduced with a length constant of 400 -550 m (Alle and Geiger, 2006;Shu et al, 2006;Kole et al, 2007). The present work proposes that this value may overestimate the true range of the ⌬V soma influence in some types of neurons because of to two facts: (1) AP is smaller than , and (2) the axonal diameter is spatially inhomogeneous.…”

“…However, several pioneering studies have demonstrated previously that the membrane potential of the neuronal cell body before action potential (AP) generation affects neurotransmission at synapses that are distant from the cell body Geiger, 2006, 2008;Shu et al, 2006;Kole et al, 2007;Scott et al, 2008;Christie et al, 2011). Although the underlying mechanisms remain controversial, the long-distance effect of the axon is mediated, at least in part, by an analog-like distortion of the AP waveform (Shu et al, 2006(Shu et al, , 2007Kole et al, 2007); APs originating from more depolarized membrane potentials are broader, and the broadened APs facilitate downstream synaptic transmission. This form of synaptic augmentation may be mediated by enhanced calcium dynamics at presynaptic terminals (Awatramani et al, 2005;Hori and Takahashi, 2009;Christie et al, 2011) (but see Alle and Geiger, 2008;Scott et al, 2008).…”

“…This somatic depolarization is reported to decay along the axon with length constants () of 430 m in rat hippocampal mossy fibers (Alle and Geiger, 2006), 417 m in layer 5 pyramidal cells in ferret prefrontal cortex (Shu et al, 2006), and 553 m of layer 5 pyramidal cells in rat somatosensory cortex (Kole et al, 2007). On the other hand, cable theory predicts that these values are variable depending on cylinder diameter and the cable wiring pattern (Rall, 1959).…”

Axonal bleb recording

“…2A, B). Subthreshold depolarization can cause accumulated inactivation of these channels and result in broadening of axonal action potentials, leading to an increase in transmitter release [4,37] . Therefore, these K V 1 channels mediate the membrane potential-dependent analog signaling between cortical neurons.…”

Reemerging role of cable properties in action potential initiation

“…Because the S3 segment has the greatest distance from the soma, and the thinnest axonal diameter (19,20) compared with S1 and S2, S3 has the greatest axoplasmic resistance isolating it from the somatodendritic compartments, which have a large membrane area and associated capacitive sink (Fig. 1).…”