Multimodal sensory integration in single cerebellar granule cells in vivo

Abstract

The mammalian cerebellum is a highly multimodal structure, receiving inputs from multiple sensory modalities and integrating them during complex sensorimotor coordination tasks. Previously, using cell-type-specific anatomical projection mapping, it was shown that multimodal pathways converge onto individual cerebellar granule cells (Huang et al., 2013). Here we directly measure synaptic currents using in vivo patch-clamp recordings and confirm that a subset of single granule cells receive convergent functional multimodal (somatosensory, auditory, and visual) inputs via separate mossy fibers. Furthermore, we show that the integration of multimodal signals by granule cells can enhance action potential output. These recordings directly demonstrate functional convergence of multimodal signals onto single granule cells.DOI: http://dx.doi.org/10.7554/eLife.12916.001

Exploring the significance of morphological diversity for cerebellar granule cell excitability

“…Similarly, in the cerebellum like circuit of mormyrid fish Sawtell (2010)52 identified a subset of CGCs that responded to sensory and motor information conveyed by different MF inputs. Multimodal integration of auditory, visual and somatosensory input within a single CGC has also been elegantly demonstrated in the rodent cerebellum53, and anatomical tracing48 also demonstrates that subsets of CGCs can receive MF input from both motor and sensory pathways. There is also experimental evidence to suggest that CGCs respond differently according to the nature of the MF input54.…”

Optimal Degrees of Synaptic Connectivity

“…The spatial organization of cerebellar cortex (Billings et al, 2014; Figure 5) rules out the extreme case in which every mossy-fiber input can be assigned randomly to any granule cell. However, within defined spatial domains, inputs to individual granule cells appear heterogeneous (Huang et al, 2013; Chabrol et al, 2015; Ishikawa et al, 2015), supporting a spatially restricted form of randomness. This is sufficient for our theory because granule cells represent heterogeneous combinations of mossy-fiber input relevant to the classification performed by their postsynaptic Purkinje cells, which are unlikely to require all possible input combinations.…”

“…Anatomical and physiological studies suggest that the handful of inputs received by granule cells in the electrosensory lobe of electric fish (Kennedy et al, 2014) and by Kenyon cells, the granule-cell analogs of the mushroom body, are a random subset of the afferents to these structures (Murthy et al, 2008; Caron et al, 2013; Gruntman and Turner, 2013). In many regions of cerebellar cortex, granule cells receive diverse (Huang et al, 2013; Chabrol et al, 2015; Ishikawa et al, 2015, but see Jörntell and Ekerot, 2006; Bengtsson and Jörntell, 2009 and Discussion), though not completely random (Billings et al, 2014) mossy-fiber input. In Marr-Albus theories, learning in cerebellar cortex relies exclusively on climbing-fiber-dependent modifications of the connections between parallel fibers and Purkinje cells, but unsupervised forms of plasticity have been reported for synapses from mossy fibers onto granule cells (Hansel et al, 2001; Schweighofer et al, 2001; Gao et al, 2012; D’Angelo, 2014; Gao et al, 2016, but see Rylkova et al, 2015).…”

Depressed by Learning—Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells

“…A prominent and compelling theory proposes sparse coding of information by granule cells [76–79]. However, recent imaging studies challenge the hypothesis that activation of the granule cell population is sparse in behaving animals [73,74,80,81].…”