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mGluR5-dependent modulation of dendritic excitability in CA1 pyramidal neurons mediated by enhancement of persistent $Na^{+}$currents
| Content Provider | Scilit |
|---|---|
| Author | Yu, Weonjin Kwon, Jaehan Sohn, Jong-Woo Lee, Suk Ho Kim, Sooyun Ho, Won-Kyung |
| Copyright Year | 2018 |
| Description | Journal: The Journal of physiology 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117564/pdf |
| Ending Page | 4156 |
| Page Count | 16 |
| Starting Page | 4141 |
| ISSN | 00223751 |
| e-ISSN | 14697793 |
| DOI | 10.1113/jp275999 |
| Journal | The Journal of physiology |
| Issue Number | 17 |
| Volume Number | 596 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2018-06-28 |
| Access Restriction | Open |
| Subject Keyword | Journal: The Journal of physiology Dendritic Excitability Mglur5 Signaling Persistent Sodium Current |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
