Identification of an inhibitory circuit that regulates cerebellar Golgi cell activity

Neuron. 2012 Jan 12;73(1):149-58. doi: 10.1016/j.neuron.2011.10.030.


Here we provide evidence that revises the inhibitory circuit diagram of the cerebellar cortex. It was previously thought that Golgi cells, interneurons that are the sole source of inhibition onto granule cells, were exclusively coupled via gap junctions. Moreover, Golgi cells were believed to receive GABAergic inhibition from molecular layer interneurons (MLIs). Here we challenge these views by optogenetically activating the cerebellar circuitry to determine the timing and pharmacology of inhibition onto Golgi cells and by performing paired recordings to directly assess synaptic connectivity. In contrast to current thought, we find that Golgi cells, not MLIs, make inhibitory GABAergic synapses onto other Golgi cells. As a result, MLI feedback does not regulate the Golgi cell network, and Golgi cells are inhibited approximately 2 ms before Purkinje cells, following a mossy fiber input. Hence, Golgi cells and Purkinje cells receive unique sources of inhibition and can differentially process shared granule cell inputs.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Bacterial Proteins / genetics
  • Biophysics
  • Cerebral Cortex / cytology*
  • Channelrhodopsins
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / genetics
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological
  • Nerve Net / cytology*
  • Nerve Net / physiology
  • Neural Inhibition / physiology*
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Piperazines / pharmacology
  • Pyridazines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Thy-1 Antigens / genetics
  • Transfection


  • Bacterial Proteins
  • Channelrhodopsins
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Luminescent Proteins
  • Piperazines
  • Pyridazines
  • Quinoxalines
  • Thy-1 Antigens
  • yellow fluorescent protein, Bacteria
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • gabazine