Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells

J Neurosci. 2010 Oct 13;30(41):13630-43. doi: 10.1523/JNEUROSCI.3226-10.2010.


Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF)-to-Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinase A (PKA) and casein kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei, but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, nonpotentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism
  • Casein Kinase II / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Electrophysiology
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Nerve Net / physiology*
  • Neuronal Plasticity / physiology*
  • Purkinje Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology
  • Statistics, Nonparametric
  • Synapses / physiology
  • Synaptic Transmission / physiology*


  • Casein Kinase II
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium