Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice

Ohmae, Shogo; Medina, Javier F.

doi:10.1038/nn.4167

Cited by 212 publications

(286 citation statements)

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“…We went on to determine how PC-DCN synapses operate during physiological activity patterns recorded from an awake mouse that underwent delay eyeblink conditioning (Ohmae and Medina, 2015). Mice were trained with a 500 ms conditioning light stimulus (CS) that was accompanied by an air puff to the eye 220 ms after the onset of stimulation.…”

Section: Resultsmentioning

confidence: 99%

“…(A) Average firing rate (top) and individual trials (bottom) of a PC in an awake mouse that underwent delay eyeblink conditioning from Ohmae & Medina, 2015. In these trials the conditioning light stimulus alone was applied without a periocular airpuff that was present at t = 0 in acquisition trials.…”

Section: Figurementioning

confidence: 99%

“…We thank Shogo Ohmae and Javier F Medina for providing recordings of Purkinje cell firing in vivo during a conditioned eyeblink task from their paper (Ohmae & Medina, 2015). We also thank the Regehr lab for comments on the manuscript.…”

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confidence: 99%

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Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

2016

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Summary The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency-independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We use a low affinity antagonist to show that GABAA receptor saturation occurs at this synapse, but it does not underlie frequency invariant transmission. We propose that PC-DCN synapses have two components of release: one prominent early in trains, and another specialized to maintain transmission during prolonged activation. Short-term facilitation offsets partial vesicle depletion to produce frequency-independent transmission.

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Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

2016

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“…During adaptation, parallel fibers to Purkinje cell synapses associated with predictive signals are strengthened and parallel fibers to Purkinje cell synapses associated with nonpredictive signals are silenced (Dean et al, 2010). These plasticity mechanisms are affected by climbing fibers originating from the inferior olive, which integrate input from the sensorimotor system and the cerebellar nuclei and act as a teaching signal in the olivocerebellar system (De Zeeuw et al, 1998; Ohmae and Medina, 2015). …”

Section: Discussionmentioning

confidence: 99%

Individual Differences in Motor Noise and Adaptation Rate Are Optimally Related

Vliet¹,

Frens

Vreede³

et al. 2018

eNeuro

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Individual variations in motor adaptation rate were recently shown to correlate with movement variability or “motor noise” in a forcefield adaptation task. However, this finding could not be replicated in a meta-analysis of adaptation experiments. Possibly, this inconsistency stems from noise being composed of distinct components that relate to adaptation rate in different ways. Indeed, previous modeling and electrophysiological studies have suggested that motor noise can be factored into planning noise, originating from the brain, and execution noise, stemming from the periphery. Were the motor system optimally tuned to these noise sources, planning noise would correlate positively with adaptation rate, and execution noise would correlate negatively with adaptation rate, a phenomenon familiar in Kalman filters. To test this prediction, we performed a visuomotor adaptation experiment in 69 subjects. Using a novel Bayesian fitting procedure, we succeeded in applying the well-established state-space model of adaptation to individual data. We found that adaptation rate correlates positively with planning noise (β = 0.44; 95% HDI = [0.27 0.59]) and negatively with execution noise (β = –0.39; 95% HDI = [–0.50 –0.30]). In addition, the steady-state Kalman gain calculated from planning and execution noise correlated positively with adaptation rate (r = 0.54; 95% HDI = [0.38 0.66]). These results suggest that motor adaptation is tuned to approximate optimal learning, consistent with the “optimal control” framework that has been used to explain motor control. Since motor adaptation is thought to be a largely cerebellar process, the results further suggest the sensitivity of the cerebellum to both planning noise and execution noise.

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“…Interestingly, delayed eye-blink conditioning, a form of associative sensory learning, was also perturbed in these mice. Cerebellar circuits play essential roles in determining the adaptive timing of conditioned responses by associating an air puff (US) with tone (Koekkoek et al, 2003) and other sensory modalities (Ohmae and Medina, 2015) during eyeblink conditioning. It is thus possible that the cerebellum, by communicating with the forebrain, may help to integrate US with sensory modalities in a time window during the acquisition phase of cued and contextual fear conditioning.…”

Section: Contribution Of the Cerebellum To Fear Conditioningmentioning

confidence: 99%

Roles of Cbln1 in Non-Motor Functions of Mice

et al. 2016

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The cerebellum is thought to be involved in cognitive functions in addition to its well established role in motor coordination and motor learning in humans. Cerebellin 1 (Cbln1) is predominantly expressed in cerebellar granule cells and plays a crucial role in the formation and function of parallel fiber-Purkinje cell synapses. Although genes encoding Cbln1 and its postsynaptic receptor, the delta2 glutamate receptor (GluD2), are suggested to be associated with autistic-like traits and many psychiatric disorders, whether such cognitive impairments are caused by cerebellar dysfunction remains unclear. In the present study, we investigated whether and how Cbln1 signaling is involved in non-motor functions in adult mice. We show that acquisition and retention/retrieval of cued and contextual fear memory were impaired in Cbln1-null mice. In situ hybridization and immunohistochemical analyses revealed that Cbln1 is expressed in various extracerebellar regions, including the retrosplenial granular cortex and the hippocampus. In the hippocampus, Cbln1 immunoreactivity was present at the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare without overt mRNA expression, suggesting that Cbln1 is provided by perforant path fibers. Retention/retrieval, but not acquisition, of cued and contextual fear memory was impaired in forebrain-predominant Cbln1-null mice. Spatial learning in the radial arm water maze was also abrogated. In contrast, acquisition of fear memory was affected in cerebellum-predominant Cbln1-null mice. These results indicate that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially and that Cbln1 signaling likely regulates motor and non-motor functions in multiple brain regions.

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Climbing fibers encode a temporal-difference prediction error during cerebellar learning in mice

Cited by 212 publications

References 50 publications

Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

Individual Differences in Motor Noise and Adaptation Rate Are Optimally Related

Roles of Cbln1 in Non-Motor Functions of Mice

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