Identification of an inhibitory circuit that regulates cerebellar Golgi cell activity

By Court Hull, Wade G. Regehr. 2012

108 citations recorded by the source corpus.

Summary 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 with 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 two milliseconds 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.

Subfields: Cellular and Molecular Neuroscience, Neurology, Sensory Systems

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Egidio D'Angelo
2. Abigail L. Person
3. J. Gilmer
4. Arnd Roth
5. Michael Häusser
6. Sawako Tabuchi
7. Sarah Rieubland
8. Karen Purba

In Neurology

1. J. Gilmer
2. Abigail L. Person
3. Sawako Tabuchi
4. Karen Purba
5. Arnd Roth
6. Michael Häusser
7. R. Silver
8. N. A. Cayco-Gajic

In Sensory Systems

1. J. Gilmer
2. Abigail L. Person
3. Sawako Tabuchi
4. Karen Purba
5. Egidio D'Angelo
6. Michael Häusser
7. R. Silver

Citations in the corpus

• Re-evaluating circuit mechanisms underlying pattern separation (2019, neutral): “Golgi cells are sparsely interconnected via chemical synapses (Hull and Regehr, 2012) and densely connected via electrical synapses (Dugue et al.”
• Autistic-like behavior and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice (2012, unknown): “Electrophysiolgical data were acquired as described previously 38 .”
• Pathway-Specific Drive of Cerebellar Golgi Cells Reveals Integrative Rules of Cortical Inhibition (2018, methodology): “128 In vitro recordings 129 One hour after slicing for granule cell recordings and immediately after slicing for Golgi cell 130 recordings (Hull and Regehr, 2012), tissue was transferred to the recording chamber.”
• Granule Cell Ascending Axon Excitatory Synapses onto Golgi Cells Implement a Potent Feedback Circuit in the Cerebellar Granular Layer (2013, background): “…and feedback inhibitory circuits in the GL. EPSCs were recorded from voltage-clamped GoCs at 70 mV in parasagittal slices, in the presence of gabazine (10 M) and strychnine (500 nM), to exclude a possible contribution of inhibitory synapses (Dumoulin et al., 2001; Hull and Regehr, 2012).”
• Purkinje cells directly inhibit granule cells in specialized regions of the cerebellar cortex (2016, unknown): “Since neither MLIs nor PCs make direct connections to GoCs to provide feedback control of the input layer (Hull and Regehr, 2012; Witter et al., 2016), it is thought that cerebellar computations are carried out sequentially: inputs are first processed in the GrC layer and then interpreted by the…”
• Structured Connectivity in Cerebellar Inhibitory Networks (2014, background): “, 2002), and the segregation by cell type observed for interneurons in the cortex, striatum, and cerebellum (Blatow et al., 2003; Gibson et al., 1999; Hull and Regehr, 2012; Koós and Tepper, 1999) suggest that clustered electrical connectivity may be a general feature of interneuron networks in the ”