Raising cytosolic Cl−in cerebellar granule cells affects their excitability and vestibulo-ocular learning
Autor: | Guillermo Federico Spitzmaul, Martijn Schonewille, William Wisden, Chris I. De Zeeuw, Patricia Seja, Thomas J. Jentsch, Ilse Klein, Aleksandra Badura, Christian A. Hübner, York Rudhard |
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Rok vydání: | 2012 |
Předmět: |
medicine.medical_specialty
Cell type Dendritic spine General Immunology and Microbiology General Neuroscience Depolarization Biology Inhibitory postsynaptic potential General Biochemistry Genetics and Molecular Biology Endocrinology Cerebellar cortex Internal medicine Reflex medicine GABAergic sense organs Molecular Biology Glycine receptor Neuroscience |
Zdroj: | The EMBO Journal. 31:1217-1230 |
ISSN: | 0261-4189 |
Popis: | Cerebellar cortical throughput involved in motor control comprises granule cells (GCs) and Purkinje cells (PCs), both of which receive inhibitory GABAergic input from interneurons. The GABAergic input to PCs is essential for learning and consolidation of the vestibulo-ocular reflex, but the role of GC excitability remains unclear. We now disrupted the Kcc2 K-Cl cotransporter specifically in either cell type to manipulate their excitability and inhibition by GABAA-receptor Cl− channels. Although Kcc2 may have a morphogenic role in synapse development, Kcc2 disruption neither changed synapse density nor spine morphology. In both GCs and PCs, disruption of Kcc2, but not Kcc3, increased [Cl−]i roughly two-fold. The reduced Cl− gradient nearly abolished GABA-induced hyperpolarization in PCs, but in GCs it merely affected excitability by membrane depolarization. Ablation of Kcc2 from GCs impaired consolidation of long-term phase learning of the vestibulo-ocular reflex, whereas baseline performance, short-term gain-decrease learning and gain consolidation remained intact. These functions, however, were affected by disruption of Kcc2 in PCs. GC excitability plays a previously unknown, but specific role in consolidation of phase learning. |
Databáze: | OpenAIRE |
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