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• W2890435854 abstract "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 (INa,P ) in the dendrites. Increased INa,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.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 Ca2+ signalling in the apical dendrites, which, with calmodulin, upregulates specifically Nav1.6 channel-mediated persistent Na+ currents (INa,P ) in the dendrites. This HFS-induced increase in dendritic INa,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 INa,P as a novel target for mediating activity-dependent modulation of dendritic integration and neuronal output." @default.
• W2890435854 created "2018-09-27" @default.
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• W2890435854 date "2018-06-28" @default.
• W2890435854 modified "2023-10-14" @default.
• W2890435854 title "mGluR5-dependent modulation of dendritic excitability in CA1 pyramidal neurons mediated by enhancement of persistent Na⁺currents" @default.
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• W2890435854 doi "https://doi.org/10.1113/jp275999" @default.
• W2890435854 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6117564" @default.
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