Dataset Information

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

ABSTRACT: 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 currents) in the maturing cerebellum, precluding analog facilitation. These results suggest that analog-to-digital facilitation is tempered by development or experience in stellate cells.

SUBMITTER: Rowan MJM

PROVIDER: S-EPMC5328503 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rapid State-Dependent Alteration in K<sub>v</sub>3 Channel Availability Drives Flexible Synaptic Signaling Dependent on Somatic Subthreshold Depolarization.

Rowan Matthew J M MJM Christie Jason M JM

Cell reports 20170201 8

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 potentia ...[more]

PMID: 28228266

Similar Datasets

Project description:Backgroundβ Amyloid (Aβ)-mediated neuronal hyperactivity, a key feature of the early stage of Alzheimer's disease (AD), is recently proposed to be initiated by the suppression of glutamate reuptake. Nevertheless, the underlying mechanism by which the impaired glutamate reuptake causes neuronal hyperactivity remains unclear. Chronic suppression of the glutamate reuptake causes accumulation of ambient glutamate that could diffuse from synaptic sites at the dendrites to the soma to elevate the tonic activation of somatic N-methyl-D-aspartate receptors (NMDARs). However, less attention has been paid to the potential role of tonic activity change in extrasynaptic glutamate receptors (GluRs) located at the neuronal soma on generation of neuronal hyperactivity.MethodsWhole-cell patch-clamp recordings were performed on CA1 pyramidal neurons in acute hippocampal slices exposed to TFB-threo-β-benzyloxyaspartic acid (TBOA) or human Aβ1-42 peptide oligomer. A series of dendritic patch-clamp recordings were made at different distances from the soma to identify the location of the changes in synaptic inputs. Moreover, single-channel recording in the cell-attached mode was performed to investigate the activity changes of single NMDARs at the soma.ResultsBlocking glutamate uptake with either TBOA or the human Aβ1-42 peptide oligomer elicited potentiation of synaptic inputs in CA1 hippocampal neurons. Strikingly, this potentiation specifically occurred at the soma, depending on the activation of somatic GluN2B-containing NMDARs (GluN2B-NMDARs) and accompanied by a substantial and persistent increment in the open probability of somatic NMDARs. Blocking the activity of GluN2B-NMDARs at the soma completely reversed both the TBOA-induced or the Aβ1-42-induced somatic potentiation and neuronal hyperactivity.ConclusionsThe somatic potentiation of synaptic inputs may represent a novel amplification mechanism that elevates cell excitability and thus contributes to neuronal hyperactivity initiated by impaired glutamate reuptake in AD.

Dataset Information

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

Publications

Rapid State-Dependent Alteration in K<sub>v</sub>3 Channel Availability Drives Flexible Synaptic Signaling Dependent on Somatic Subthreshold Depolarization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets