Rapid State-Dependent Alteration in Kv3 Channel Availability Drives Flexible Synaptic Signaling Dependent on Somatic Subthreshold Depolarization

Abstract

Summary In many neurons, subthreshold depolarization in the soma can transiently increase action potential (AP)-evoked neurotransmission via analog-to-digital facilitation. The mechanisms underlying this form of short-term synaptic plasticity are unclear, in part, due to the relative inaccessibility of the axon to direct physiological interrogation. Using voltage imaging and patch-clamp recording from presynaptic boutons of cerebellar stellate interneurons, we observed that depolarizing somatic potentials readily spread into the axon, resulting in AP broadening, increased spike-evoked Ca2+ entry, and enhanced neurotransmission strength. Kv3 channels, which drive AP repolarization, rapidly inactivated upon incorporation of Kv3.4 subunits. This leads to fast susceptibility to depolarization-induced spike broadening and analog facilitation independent of Ca2+-dependent protein kinase C signaling. The spread of depolarization into the axon was attenuated by hyperpolarization-activated currents (Ih) in the maturing cerebellum, precluding analog facilitation. These results suggest that analog-to-digital facilitation is tempered by development or experience in stellate cells.

Kv3.1 and Kv3.3 subunits differentially contribute to Kv3 channels and action potential repolarization in principal neurons of the auditory brainstem

“…Several reports have suggested that Kv3.3 or Kv3.4 subunits could be differentially incorporated into somatic versus presynaptic channels in the cerebellum and spinal cord (Brooke et al . 2004; 2010; Rowan & Christie, 2017). But the extent to which all Kv3 subunits contribute to presynaptic AP repolarization and thus influence transmitter release is an open question.…”

Full function of exon junction complex factor, Rbm8a, is critical for interneuron development

“…Meanwhile, another gene involved in myelin maintenance, Mal2, is upregulated more than twofold. Two CNS-related DEGs were Kcnc4, a voltage-gated potassium ion channel 48 , and Gda, a guanine deaminase concentrated in the brain that regulates microtubule assembly 49 . Kcnc4 conducts potassium outward following an action potential, restoring the membrane to resting state 48 .…”

“…Two CNS-related DEGs were Kcnc4, a voltage-gated potassium ion channel 48 , and Gda, a guanine deaminase concentrated in the brain that regulates microtubule assembly 49 . Kcnc4 conducts potassium outward following an action potential, restoring the membrane to resting state 48 . Likewise, the increase in Gda expression could indicate a misregulation of the cytoskeleton or an increase in cellular outgrowths.…”

Signal propagation along the axon

“…This analog-digital facilitation induced by depolarization (d-ADF) is not exclusively observed in glutamate-releasing neurons but it is also seen on GABA-releasing interneurons. In this case, the mechanism depends either on spike-waveform through presynaptic Kv3.4 [29 ] or on the increase in basal calcium during subthreshold depolarization via activation of P/Q type calcium channels [30,31]. Modulation of basal calcium concentration by presynaptic membrane potential is also the main mechanism of d-ADF in auditory neurons [32,33], mitral cells of the olfactory bulb [34] and sensory neurons of the Aplysia [35].…”