Identification of an Inhibitory Circuit that Regulates Cerebellar Golgi Cell Activity

• Published in: Neuron (Cambridge, Mass.) Vol. 73; no. 1; pp. 149 - 158
• Main Authors: Hull, Court, Regehr, Wade G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12-01-2012; Elsevier Limited
• Subjects: Animals; Animals, Newborn; Ataxia; 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; Experiments; 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; Rodents; Thy-1 Antigens - genetics; Transfection
• ISSN: 0896-6273; 1097-4199
• 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.
► We identify an inhibitory cerebellar circuit: GABAergic synapses between Golgi cells ► Molecular layer interneurons do not inhibit Golgi cells, as was previously thought ► Inhibition arrives earlier onto Golgi cells than onto Purkinje cells ► Inhibition onto Golgi cells arrives simultaneously with parallel fiber excitation
Golgi cells are a crucial source of inhibition in the cerebellum. It was previously thought that Golgi cell activity was regulated by inhibition from molecular layer interneurons (MLIs). Hull and Regehr overturn this view by revealing instead that Golgi cells inhibit each other.