Hyperpolarization induces a long-term increase in the spontaneous firing rate of cerebellar Golgi cells

J Neurosci. 2013 Apr 3;33(14):5895-902. doi: 10.1523/JNEUROSCI.4052-12.2013.

Abstract

Golgi cells (GoCs) are inhibitory interneurons that influence the cerebellar cortical response to sensory input by regulating the excitability of the granule cell layer. While GoC inhibition is essential for normal motor coordination, little is known about the circuit dynamics that govern the activity of these cells. In particular, although GoC spontaneous spiking influences the extent of inhibition and gain throughout the granule cell layer, it is not known whether this spontaneous activity can be modulated in a long-term manner. Here we describe a form of long-term plasticity that regulates the spontaneous firing rate of GoCs in the rat cerebellar cortex. We find that membrane hyperpolarization, either by mGluR2 activation of potassium channels, or by somatic current injection, induces a long-lasting increase in GoC spontaneous firing. This spike rate plasticity appears to result from a strong reduction in the spike after hyperpolarization. Pharmacological manipulations suggest the involvement of calcium-calmodulin-dependent kinase II and calcium-activated potassium channels in mediating these firing rate increases. As a consequence of this plasticity, GoC spontaneous spiking is selectively enhanced, but the gain of evoked spiking is unaffected. Hence, this plasticity is well suited for selectively regulating the tonic output of GoCs rather than their sensory-evoked responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cerebellum / cytology*
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • GABA Antagonists / pharmacology
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Male
  • Patch-Clamp Techniques
  • Phosphinic Acids / pharmacology
  • Potassium Channels, Calcium-Activated / metabolism
  • Propanolamines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / metabolism
  • Time Factors

Substances

  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Phosphinic Acids
  • Potassium Channels, Calcium-Activated
  • Propanolamines
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • CGP 55845A
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2