INIBIBB   05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
artículos
Título:
Raising cytosolic Cl- in cerebellar granule cells affects their excitability and vestibulo-ocular learning
Autor/es:
SEJA, P.; SCHONEWILLE, M.; SPITZMAUL, G.; BADURA, A.; KLEIN, I.; RUDHARD, Y.; WISDEN, W.; HÜBNER, C.A.; DE ZEEUW, C.; JENTSCH, T.J.
Revista:
EMBO JOURNAL
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2012 vol. 31 p. 1217 - 1230
ISSN:
0261-4189
Resumen:
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, in-
creased [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 conso-
lidation of long-term phase learning of the vestibulo-ocular
reflex, whereas baseline performance, short-term gain-de-
crease 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.