The Origin of Physiological Local mGluR1 Supralinear Ca2+Signals in Cerebellar Purkinje Neurons
| Autor: | Karima Ait Ouares, Marco Canepari |
|---|---|
| Přispěvatelé: | Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] Endogeny Dendrite Parallel fiber 03 medical and health sciences 0302 clinical medicine medicine ComputingMilieux_MISCELLANEOUS 030304 developmental biology Membrane potential Synaptic potential 0303 health sciences Voltage-dependent calcium channel Chemistry General Neuroscience Climbing fiber Hyperpolarization (biology) 030104 developmental biology medicine.anatomical_structure Climbing fibre Metabotropic glutamate receptor Synaptic plasticity Biophysics Metabotropic glutamate receptor 1 Motor learning 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2020, 40 (9), pp.1795-1809. ⟨10.1523/JNEUROSCI.2406-19.2020⟩ |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2406-19.2020 |
| Popis: | In mouse cerebellar Purkinje neurons (PNs), the climbing fiber (CF) input provides a signal to parallel fiber (PF) synapses, triggering PF synaptic plasticity. This signal is given by supralinear Ca2+transients, associated with the CF synaptic potential and colocalized with the PF Ca2+influx, occurring only when PF activity precedes the CF input. Here, we unravel the biophysical determinants of supralinear Ca2+signals associated with paired PF-CF synaptic activity. We used membrane potential (Vm) and Ca2+imaging to investigate the local CF-associated Ca2+influx following a train of PF synaptic potentials in two cases: (1) when the dendriticVmis hyperpolarized below the restingVm, and (2) when the dendriticVmis at rest. We found that supralinear Ca2+signals are mediated by type-1 metabotropic glutamate receptors (mGluR1s) when the CF input is delayed by 100–150 ms from the first PF input in both cases. When the dendrite is hyperpolarized only, however, mGluR1s boost neighboring T-type channels, providing a mechanism for local coincident detection of PF-CF activity. The resulting Ca2+elevation is locally amplified by saturation of endogenous Ca2+buffers produced by the PF-associated Ca2+influx via the mGluR1-mediated nonselective cation conductance. In contrast, when the dendriticVmis at rest, mGluR1s increase dendritic excitability by inactivating A-type K+channels, but this phenomenon is not restricted to the activated PF synapses. Thus,Vmis likely a crucial parameter in determining PF synaptic plasticity, and the occurrence of hyperpolarization episodes is expected to play an important role in motor learning.SIGNIFICANCE STATEMENTIn Purkinje neurons, parallel fiber synaptic plasticity, determined by coincident activation of the climbing fiber input, underlies cerebellar learning. We unravel the biophysical mechanisms allowing the CF input to produce a local Ca2+signal exclusively at the sites of activated parallel fibers. We show that when the membrane potential is hyperpolarized with respect to the resting membrane potential, type-1 metabotropic glutamate receptors locally enhance Ca2+influx mediated by T-type Ca2+channels, and that this signal is amplified by saturation of endogenous buffer also mediated by the same receptors. The combination of these two mechanisms is therefore capable of producing a Ca2+signal at the activated parallel fiber sites, suggesting a role of Purkinje neuron membrane potential in cerebellar learning. |
| Databáze: | OpenAIRE |
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