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Voltage gated calcium channel activation by backpropagating action potentials downregulates NMDAR function

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Item Type:Article
Title:Voltage gated calcium channel activation by backpropagating action potentials downregulates NMDAR function
Creators Name:Theis, A.K. and Rózsa, B. and Katona, G. and Schmitz, D. and Johenning, F.W.
Abstract:The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs) propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs). For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs) result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca2+ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca2+ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca2+conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs) measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca2+ influx, the amount of EPSP mediated Ca2+ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.
Keywords:Dendritic Spines, Two-Photon Microscopy, Calcium, Synaptic Transmission, Voltage Gated Ca2+ Channels (VGCCs), Metaplasticity, Homeostatic Synaptic Plasticity, NMDAR, Animals, Rats
Source:Frontiers in Cellular Neuroscience
ISSN:1662-5102
Publisher:Frontiers Research Foundation (Switzerland)
Volume:12
Page Range:109
Date:23 April 2018
Official Publication:https://doi.org/10.3389/fncel.2018.00109
PubMed:View item in PubMed

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