Dynamics of fast and slow inhibition from cerebellar golgi cells allow flexible control of synaptic integration

Neuron. 2009 Sep 24;63(6):843-53. doi: 10.1016/j.neuron.2009.09.004.

Abstract

Throughout the brain, multiple interneuron types influence distinct aspects of synaptic processing. Interneuron diversity can thereby promote differential firing from neurons receiving common excitation. In contrast, Golgi cells are the sole interneurons regulating granule cell spiking evoked by mossy fibers, thereby gating inputs to the cerebellar cortex. Here, we examine how this single interneuron class modifies activity in its targets. We find that GABA(A)-mediated transmission at unitary Golgi cell --> granule cell synapses consists of varying contributions of fast synaptic currents and sustained inhibition. Fast IPSCs depress and slow IPSCs gradually build during high-frequency Golgi cell activity. Consequently, fast and slow inhibition differentially influence granule cell spike timing during persistent mossy fiber input. Furthermore, slow inhibition reduces the gain of the mossy fiber --> granule cell input-output curve, while fast inhibition increases the threshold. Thus, a lack of interneuron diversity need not prevent flexible inhibitory control of synaptic processing.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Biophysics
  • Cell Line, Transformed
  • Cerebellum / cytology*
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Humans
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Nonlinear Dynamics*
  • Patch-Clamp Techniques / methods
  • Phosphinic Acids / pharmacology
  • Photic Stimulation / methods
  • Piperazines / pharmacology
  • Propanolamines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rhodopsin / genetics
  • Synapses / drug effects
  • Synapses / physiology*
  • Time Factors
  • Transfection / methods

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Phosphinic Acids
  • Piperazines
  • Propanolamines
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • CGP 55845A
  • Rhodopsin
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid