Raising Cl- concentration in cerebellar granule cells affects their excitability and consolidation of vestibulo-ocular phase learning

SEJA, P.; SCHONEWILLE, M.; SPITZMAUL, G.; BADURA, A.; KLEIN, I.; RUDHARD, Y.; WISDEN, W.; HÜBNER, C.A.; DE ZEEUW, C.; JENTSCH, T.J.

New London, NH

Conferencia; Cerebellum: Cerebellum in Health & Disease; 2011

Gordon Research Conferences

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.