Sensorimotor Representations in Cerebellar Granule Cells in Larval Zebrafish Are Dense, Spatially Organized, and Non-temporally Patterned

Abstract

A fundamental question in neurobiology is how animals integrate external sensory information from their environment with self-generated motor and sensory signals in order to guide motor behavior and adaptation. The cerebellum is a vertebrate hindbrain region where all of these signals converge and that has been implicated in the acquisition, coordination, and calibration of motor activity. Theories of cerebellar function postulate that granule cells encode a variety of sensorimotor signals in the cerebellar input layer. These models suggest that representations should be high-dimensional, sparse, and temporally patterned. However, in vivo physiological recordings addressing these points have been limited and in particular have been unable to measure the spatiotemporal dynamics of population-wide activity. In this study, we use both calcium imaging and electrophysiology in the awake larval zebrafish to investigate how cerebellar granule cells encode three types of sensory stimuli as well as stimulus-evoked motor behaviors. We find that a large fraction of all granule cells are active in response to these stimuli, such that representations are not sparse at the population level. We find instead that most responses belong to only one of a small number of distinct activity profiles, which are temporally homogeneous and anatomically clustered. We furthermore identify granule cells that are active during swimming behaviors and others that are multimodal for sensory and motor variables. When we pharmacologically change the threshold of a stimulus-evoked behavior, we observe correlated changes in these representations. Finally, electrophysiological data show no evidence for temporal patterning in the coding of different stimulus durations.

Inhibition gates supralinear Ca2+ signaling in Purkinje cell dendrites during practiced movements

“…This behavior also elicited the activity of granule cell parallel fibers, as determined in separate Ca 2+ imaging experiments from GCaMP6f-transduced neurons in the same area of Crus II (Figure 1—figure supplement 1A–D). As with MLIs in this region (Gaffield and Christie, 2017), average parallel fiber Ca 2+ activity closely tracked lick rate (Figure 1—figure supplement 1E), indicating encoding of licking-related kinematics in their population as observed in other cerebellar lobules (Jelitai et al, 2016; Chen et al, 2017; Giovannucci et al, 2017; Knogler et al, 2017). …”

Expansion coding and computation in the cerebellum: 50 years after the Marr–Albus codon theory

“…There appears to be plasticity throughout the cerebellum, including at the mossy fibre to granule cell synapses, and within the deep cerebellar nuclei (Gao et al 2012;D'Angelo, 2014;Sgritta et al 2017;Raymond & Medina, 2018). Multi-cell recording and imaging methods have shown that very high numbers of granule cells are simultaneously active, sometimes approaching 50% at any given time Giovannucci et al 2017;Knogler et al 2017;Gilmer & Person, 2018). As a result, there may be significant overlap between the pattern of activity in different states.…”

“…; Knogler et al . ; Gilmer & Person, ). As a result, there may be significant overlap between the pattern of activity in different states.…”

“…; Marr, ; Herculano‐Houzel, ; Badura & De Zeeuw, ; Knogler et al . ; Litwin‐Kumar et al . ; Raymond & Medina, ).…”

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]. In vitro , the number of co-activated parallel fibers, which can be controlled by the strength of parallel fiber stimulation, can influence whether LTD is induced or not [67,68], suggesting that cooperativity at parallel fiber synapses is an important consideration.…”