GABAergic synaptic communication in the GABAergic and non-GABAergic cells in the deep cerebellar nuclei

Neuroscience. 2008 Oct 15;156(3):537-49. doi: 10.1016/j.neuroscience.2008.07.060. Epub 2008 Aug 6.

Abstract

The deep cerebellar nuclei (DCN) are the final integrative units of the cerebellar network. The strongest single afferent to the DCN is formed by GABAergic Purkinje neuron axons whose synapses constitute the majority of all synapses in the DCN, with their action strongly regulating the intrinsic activity of their target neurons. Although this is well established, it remains unclear whether all DCN cell groups receive a functionally similar inhibitory input. We previously characterized three types of mouse DCN neurons based on the expression of glutamic acid decarboxylase isoform 67 (GAD67), their active membrane properties and morphological features. Here we describe the GABAergic synapses in these cell groups and show that spontaneous GABAergic synaptic activity can be seen in all three cell types. Since the majority of DCN neurons fire action potentials spontaneously at high frequencies both in vivo and in vitro, we expected that spontaneous GABAergic synaptic activities mediated by intra-DCN synaptic connections could be uncovered by their sensitivity to TTX. However, TTX had little effect on spontaneous synaptic activity. It seems, therefore that functional GABAergic connectivity within the DCN is sparse and/or weak at least under our experimental conditions. Even though present in all cell types, the spontaneous GABAergic events showed significant differences between the cell types. The synaptic currents in GABAergic cells had lower amplitude, lower frequency and slower kinetics than those of non-GABAergic cells. These differences could not be sufficiently explained by considering only cell size differences or a differential GABA(A)-receptor alpha-subunit composition. Rather, the main differentiating factor appears to be the dendritic localization of GABAergic synapses in the GABAergic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Action Potentials / radiation effects
  • Analysis of Variance
  • Animals
  • Biomechanical Phenomena
  • Cerebellar Nuclei / cytology*
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • GABA Agonists / pharmacology
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Pyridines / pharmacology
  • Sodium Channel Blockers / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Temperature
  • Tetrodotoxin / pharmacology
  • Zolpidem
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • GABA Agonists
  • Pyridines
  • Sodium Channel Blockers
  • Green Fluorescent Proteins
  • Tetrodotoxin
  • gamma-Aminobutyric Acid
  • Zolpidem
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1