Only a Minority of the Inhibitory Inputs to Cerebellar Golgi Cells Originates from Local GABAergic Cells

eNeuro. 2016 May 23;3(2):ENEURO.0055-16.2016. doi: 10.1523/ENEURO.0055-16.2016. eCollection Mar-Apr 2016.

Abstract

Cerebellar Golgi cells (GoCs) efficiently control the spiking activity of granule cells through GABAA receptor-mediated tonic and phasic inhibition. Recent experiments provided compelling evidence for the extensive interconnection of GoCs through electrical synapses, but their chemical inhibitory synaptic inputs are debated. Here, we investigated the GABAergic synaptic inputs of GoCs using in vitro electrophysiology and quantitative light microscopy (LM) and electron microscopy (EM). We characterized GABAA receptor-mediated IPSCs in GoCs and Lugaro cells (LuCs), and found that IPSCs in GoCs have lower frequencies, smaller amplitudes, and much slower decay kinetics. Pharmacological and LM immunolocalization experiments revealed that GoCs express α3, whereas LuCs express α1 subunit-containing GABAA receptors. The selective expression and clustered distribution of the α3 subunit in GoCs allowed the quantitative analysis of GABAergic synapses on their dendrites in the molecular layer (ML). EM and LM experiments in rats, and wild-type and GlyT2-GFP transgenic mice revealed that only one third of axon terminals establishing GABAergic synapses on GoC dendrites contain GlyT2, ruling out LuCs, globular cells, and any noncortical glycinergic inputs as major inhibitory sources. We also show that axon terminals of stellate/basket cells very rarely innervate GlyT2-GFP-expressing GoCs, indicating that only a minority of the inhibitory inputs to GoCs in the ML originates from local interneurons, and the majority of their inhibitory inputs exclusively releases GABA.

Keywords: GABA; cerebellum; immunohistochemistry; inhibition; patch clamp; synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / metabolism
  • Cerebellum / cytology*
  • Cerebellum / drug effects
  • Cerebellum / physiology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Female
  • GABAergic Neurons / cytology*
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / physiology
  • Interneurons / cytology*
  • Interneurons / drug effects
  • Interneurons / physiology
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition* / physiology
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Rats, Wistar
  • Receptors, GABA-A / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Receptors, GABA-A
  • gamma-Aminobutyric Acid