Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 42, Pages 13099-13104Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1510249112
Keywords
cerebellum; Golgi cells; granule cells; inhibition; synaptic integration
Categories
Funding
- Wellcome Trust
- European Research Council
- Medical Research Council
- Gatsby Charitable Foundation
- Wellcome Trust Advanced Training and Research Career Development Fellowships
- Medical Research Council [MC_UP_1201/1, G1000512] Funding Source: researchfish
- MRC [MC_UP_1201/1, G1000512] Funding Source: UKRI
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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.
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