Integration of quanta in cerebellar granule cells during sensory processing

By Paul Chadderton, Troy W. Margrie, Michael Häusser. 2004

677 citations recorded by the source corpus.

To understand the computations performed by the input layers of cortical structures, it is essential to determine the relationship between sensory-evoked synaptic input and the resulting pattern of output spikes. In the cerebellum, granule cells constitute the input layer, translating mossy fibre signals into parallel fibre input to Purkinje cells. Until now, their small size and dense packing have precluded recordings from individual granule cells in vivo. Here we use whole-cell patch-clamp recordings to show the relationship between mossy fibre synaptic currents evoked by somatosensory stimulation and the resulting granule cell output patterns. Granule cells exhibited a low ongoing firing rate, due in part to dampening of excitability by a tonic inhibitory conductance mediated by GABAA (γ-aminobutyric acid type A) receptors. Sensory stimulation produced bursts of mossy fibre excitatory postsynaptic currents (EPSCs) that summate to trigger bursts of spikes. Notably, these spike bursts were evoked by only a few quantal EPSCs, and yet spontaneous mossy fibre inputs triggered spikes only when inhibition was reduced. Our results reveal that the input layer of the cerebellum balances exquisite sensitivity with a high signal-to-noise ratio. Granule cell bursts are optimally suited to trigger glutamate receptor activation and plasticity at parallel fibre synapses, providing a link between input representation and memory storage in the cerebellum.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neurology

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Citations in the corpus

Re-evaluating circuit mechanisms underlying pattern separation (2019, positive): “But this concept has been challenged based on the temporally dense activity of single granule cells recorded in vivo (Chadderton et al., 2004; Jörntell and Ekerot, 2006; Spanne and Jörntell, 2015; Chen et al., 2017).”
Synaptic and cellular properties of the feed-forward inhibitory circuit within the input layer of the cerebellar cortex (2008, background): “Curiously, fast stimulus-locked inhibition of GrCs has rarely been observed in vivo (Chadderton et al., 2004; Jörntell and Ekerot, 2006).”
Rapid Desynchronization of an Electrically Coupled Interneuron Network with Sparse Excitatory Synaptic Input (2010, positive): “Background synaptic noise similar to that observed in vivo (Chadderton et al., 2004; Rancz et al., 2007) and heterogeneity in intrinsic GoC firing rates that we observed experimentally were implemented via MF and PF synaptic input and variable leak conductances.”
Extrasynaptic GABAA receptors: Their function in the CNS and implications for disease (2012, background): “, 2002) and in vivo (Chadderton et al., 2004), while conventional synaptic g2 subunit-containing GABAARs are involved in direct synaptic transmission (Farrant and Nusser, 2005).”
High Frequency Burst Firing of Granule Cells Ensures Transmission at the Parallel Fiber to Purkinje Cell Synapse at the Cost of Temporal Coding (2013, background): “Although the current observations in awake behaving mice and those of others in rabbits and anesthetized rats indicate that cerebellar GrCs can fire bursts of action potentials with instantaneous frequencies up to ∼1 kHz (Chadderton et al., 2004; Hensbroek et al., 2005; Ruigrok et al., 2011), our in”
Widespread State-Dependent Shifts in Cerebellar Activity in Locomoting Mice (2012, background): “Under anesthesia, GCs can be near-silent and respond to sensory activation with a brief burst of spikes [3,4,5].”
NMDA receptors with incomplete Mg2+ block enable low-frequency transmission through the cerebellar cortex (2012, background): “The high-frequency bursting phase is not essential for GC layer throughput Sensory stimuli encoded by brief high-frequency MF bursts have been shown to be efficiently transmitted by GCs (Chadderton et al., 2004; Rancz et al., 2007; Barmack and Yakhnitsa, 2008; Rothman et al., 2009; Sawtell, 2010) du”
Properties of Somatosensory Synaptic Integration in Cerebellar Granule Cells In Vivo (2006, background): “…sparse coding in granule cells have heavily influenced current models about the function of the cerebellar granule layer (Marr, 1969; Albus, 1971; Tyrrell and Willshaw, 1992; Houk et al., 1996; Schweighofer et al., 1998, 2001; Wolpert et al., 1998; Chadderton et al., 2004; Semyanov et al., 2004).”
Population-scale organization of cerebellar granule neuron signaling during a visuomotor behavior (2017, background): “…metabotropic regulation of potassium currents at unipolar brush cells (Borges-Merjane and Trussell, 2015), recently identified Purkinje cell collaterals onto granule cells (Guo et al., 2016) or pathways that include Golgi cells (Medina et al., 2000; Chadderton et al., 2004; Bengtsson et al., 2012).”
Multimodal integration in granule cells as a basis for associative plasticity and sensory prediction in a cerebellum-like circuit. (2010, result): “Patterns of spontaneous synaptic and spiking activity in GCs were similar to those reported for cerebellar GCs in vivo (Chadderton et al., 2004; Jörntell and Ekerot, 2006).”