Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition
By Ian Duguid, T. Branco, Paul Chadderton, Charlotte Arlt, K. Powell, Michael Häusser. 2015
59 citations recorded by the source corpus.
Significance Understanding how synaptic inhibition regulates sensory responses is a fundamental question in neuroscience. In cerebellar granule cells, sensory stimulation is thought to evoke an excitation–inhibition sequence driven by direct input from mossy fibers and followed by classical disynaptic feed-forward inhibition from nearby Golgi cells. We made, to our knowledge, the first voltage-clamp recordings of sensory-evoked inhibition in granule cells in vivo and show that, surprisingly, sensory-evoked inhibition often precedes mossy fiber excitation activated by the same stimulus. We demonstrate how such “preceding” inhibition can shape granule cell responses to sensory stimulation. Our findings challenge the existing view that classical feed-forward inhibition is the dominant mode of inhibition, suggesting that parallel inhibitory networks regulate sensory information transmission through the granular layer. Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses.
Subfields: Cognitive Neuroscience, Neurology, Sensory Systems
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Citations in the corpus
- Re-evaluating circuit mechanisms underlying pattern separation (2019, positive): “Granule cells also receive feedforward and feedback inhibition from Golgi cells (Vos et al., 1999; Duguid et al., 2015), which are driven by excitatory inputs from mossy fibres through their basal dendrites (Kanichay and Silver, 2008) and ascending granule cell axons and parallel fibres through thei”
- Purkinje cells directly inhibit granule cells in specialized regions of the cerebellar cortex (2016, unknown): “GoCs are contacted by both MFs and GrCs and are thought to mediate both feedforward and feedback inhibition (Eccles et al., 1967; Palay and Chan-Palay, 1974), but numerous studies suggest that feedback GoC to GrC inhibition is weak (Dieudonne , 1998; Duguid et al., 2015).”
- Multimodal sensory integration in single cerebellar granule cells in vivo (2015, background): “Another possibility for interaction between two separate pathways (not illustrated here) is presynaptic inhibition (Mitchell and Silver, 2000) or postsynaptic inhibition (Duguid et al., 2015) via Golgi cells.”