The cerebellar cortex has a key role in generating predictive sensorimotor associations. To do so, the granule cell layer is thought to establish unique sensorimotor representations for learning. However, how this is achieved and how granule cell population responses contribute to behavior have remained unclear. To address these questions, we have used in vivo calcium imaging and granule cell-specific pharmacological manipulation of synaptic inhibition in awake, behaving mice. These experiments indicate that inhibition sparsens and thresholds sensory responses, limiting overlap between sensory ensembles and preventing spiking in many granule cells that receive excitatory input. Moreover, inhibition can be recruited in a stimulus-specific manner to powerfully decorrelate multisensory ensembles. Consistent with these results, granule cell inhibition is required for accurate cerebellum-dependent sensorimotor behavior. These data thus reveal key mechanisms for granule cell layer pattern separation beyond those envisioned by classical models.

小脑皮层在产生预测性感觉运动关联方面发挥着关键作用。为此，颗粒细胞层被认为为学习建立了独特的感觉运动表征。然而，这是如何实现的以及颗粒细胞群反应如何影响行为仍不清楚。为了解决这些问题，我们在清醒、行为正常的小鼠中使用了体内钙成像和颗粒细胞特异性突触抑制的药理学操作。这些实验表明，抑制作用会稀疏和阈值感觉反应，限制感觉整体之间的重叠，并防止许多接受兴奋性输入的颗粒细胞出现尖峰。此外，可以以特定刺激的方式招募抑制，以强有力地去相关多感觉整体。与这些结果一致，颗粒细胞抑制对于精确的小脑依赖性感觉运动行为是必需的。因此，这些数据揭示了颗粒细胞层模式分离的关键机制，超出了经典模型的设想。