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mGluR5‐dependent modulation of dendritic excitability in CA1 pyramidal neurons mediated by enhancement of persistent Na + currents
Author(s) -
Yu Weonjin,
Kwon Jaehan,
Sohn JongWoo,
Lee Suk Ho,
Kim Sooyun,
Ho WonKyung
Publication year - 2018
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp275999
Subject(s) - schaffer collateral , excitatory postsynaptic potential , long term potentiation , neuroscience , dendritic spike , metabotropic glutamate receptor , chemistry , apical dendrite , metabotropic glutamate receptor 5 , synaptic plasticity , dendritic spine , dendrite (mathematics) , hippocampal formation , postsynaptic potential , glutamate receptor , biology , receptor , inhibitory postsynaptic potential , cerebral cortex , biochemistry , geometry , mathematics
Key points High‐frequency stimulation (HFS) of the Schaffer collateral pathway activates metabotropic glutamate receptor 5 (mGluR5) signalling in the proximal apical dendrites of CA1 pyramidal neurons. The synaptic activation of mGluR5‐mediated calcium signalling causes a significant increase in persistent sodium current ( I Na,P ) in the dendrites. Increased I Na,P by HFS underlies potentiation of synaptic inputs at both the proximal and distal dendrite, leading to an enhanced probability of action potential firing associated with decreased action potential thresholds. Therefore, HFS‐induced activation of intracellular mGluR5 serves an important role as an instructive signal for potentiation of upcoming inputs by increasing dendritic excitability.Abstract Dendritic Na + channels in pyramidal neurons are known to amplify synaptic signals, thereby facilitating action potential (AP) generation. However, the mechanisms that modulate dendritic Na + channels have remained largely uncharacterized. Here, we report a new form of short‐term plasticity in which proximal excitatory synaptic inputs to hippocampal CA1 pyramidal neurons transiently elevate dendritic excitability. High‐frequency stimulations (HFS) to the Schaffer collateral (SC) pathway activate mGluR5‐dependent Ca 2+ signalling in the apical dendrites, which, with calmodulin, upregulates specifically Nav1.6 channel‐mediated persistent Na + currents ( I Na,P ) in the dendrites. This HFS‐induced increase in dendritic I Na,P results in transient increases in the amplitude of excitatory postsynaptic potentials induced by both proximal SC and distal perforant path stimulation, leading to the enhanced probability of AP firing associated with decreased AP thresholds. Taken together, our study identifies dendritic I Na,P as a novel target for mediating activity‐dependent modulation of dendritic integration and neuronal output.