Cell Reports
Volume 3, Issue 4, 25 April 2013, Pages 1239-1251
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Article
Silencing the Majority of Cerebellar Granule Cells Uncovers Their Essential Role in Motor Learning and Consolidation

https://doi.org/10.1016/j.celrep.2013.03.023Get rights and content
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Summary

Cerebellar granule cells (GCs) account for more than half of all neurons in the CNS of vertebrates. Theoretical work has suggested that the abundance of GCs is advantageous for sparse coding during memory formation. Here, we minimized the output of the majority of GCs by selectively eliminating their CaV2.1 (P/Q-type) Ca2+ channels, which mediate the bulk of their neurotransmitter release. This resulted in reduced GC output to Purkinje cells (PCs) and stellate cells (SCs) as well as in impaired long-term plasticity at GC-PC synapses. As a consequence modulation amplitude and regularity of simple spike (SS) output were affected. Surprisingly, the overall motor performance was intact, whereas demanding motor learning and memory consolidation tasks were compromised. Our findings indicate that a minority of functionally intact GCs is sufficient for the maintenance of basic motor performance, whereas acquisition and stabilization of sophisticated memories require higher numbers of normal GCs controlling PC firing.

Highlights

► Minimizing the output of cerebellar GCs impairs GC-PC long-term plasticity ► Minimizing the output of cerebellar GCs affects PCs’ coding ► Minimizing the output of cerebellar GCs does not compromise motor performance ► Minimizing the output of cerebellar GCs partially disrupts motor memory formation

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These authors contributed equally to this work