Intrinsic plasticity of cerebellar stellate cells is mediated by NMDA receptor regulation of voltage‐gated Na<sup>+</sup> channels
Bibliographic record
Abstract
Key points We show that NMDA receptors (NMDARs) elicit a long‐term increase in the firing rates of inhibitory stellate cells of the cerebellum NMDARs induce intrinsic plasticity through a Ca2+‐ and CaMKII‐dependent pathway that drives shifts in the activation and inactivation properties of voltage‐gated Na+ (Nav) channels An identical Ca2+‐ and CaMKII‐dependent signalling pathway is triggered during whole‐cell recording which lowers the action potential threshold by causing a hyperpolarizing shift in the gating properties of Nav channels. Our findings open the more general possibility that NMDAR‐mediated intrinsic plasticity found in other cerebellar neurons may involve similar shifts in Nav channel gating. Abstract Memory storage in the mammalian brain is mediated not only by long‐lasting changes in the efficacy of neurotransmitter receptors but also by long‐term modifications to the activity of voltage‐gated ion channels. Activity‐dependent plasticity of voltage‐gated ion channels, or intrinsic plasticity, is found throughout the brain in virtually all neuronal types, including principal cells and interneurons. Although intrinsic plasticity has been identified in neurons of the cerebellum, it has yet to be studied in inhibitory cerebellar stellate cells of the molecular layer which regulate activity outflow from the cerebellar cortex by feedforward inhibition onto Purkinje cells. The study of intrinsic plasticity in stellate cells has been particularly challenging as membrane patch breakthrough in electrophysiology experiments unintentionally triggers changes in spontaneous firing rates. Using cell‐attached patch recordings to avoid disruption, we show that activation of extrasynaptic N‐methyl‐d‐aspartate receptors (NMDARs) elicits a long‐term increase in the firing properties of stellate cells by stimulating a rise in cytosolic Ca2+ and activation of Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII). An identical signalling pathway is triggered during whole‐cell recording which lowers the action potential threshold by causing a hyperpolarizing shift in the gating properties of voltage‐gated sodium (Nav) channels. Together, our findings identify an unappreciated role of Nav channel‐dependent intrinsic plasticity in cerebellar stellate cells which, in concert with non‐canonical NMDAR signalling, provides the cerebellum with an unconventional mechanism to fine‐tune motor behaviour.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".