Coding of stimulus strength via analog calcium signals in Purkinje cell dendrites of awake mice

Najafi, Farzaneh; Giovannucci, Andrea; Wang, Samuel S.‐H.; Medina, Javier F.

doi:10.7554/elife.03663

Cited by 75 publications

(98 citation statements)

References 93 publications

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“…1a), an optically accessible region that, although not previously included among known regions necessary for the production of blinks 21–23 , receives excitation that drives movements of nearby trunk and neck regions (Supplementary Fig. 4) and is likely to be engaged during eyeblink conditioning because it receives climbing fiber inputs triggered by the periorbital airpuff US 24,25 . Indeed, in separate nonimaging experiments with five mice that were trained to a high fraction of conditional responses (CR rate > 70%), we found that injection of muscimol in the same region of cerebellar cortex led to a reversible reduction in CR probability and amplitude (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning

et al. 2017

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Cerebellar granule cells, which constitute half the brain’s neurons, supply Purkinje cells with contextual information necessary for motor learning, but how they encode this information is unknown. Here we show, using two-photon microscopy to track neural activity over multiple days of cerebellum-dependent eyeblink conditioning in mice, that granule cell populations acquire a dense representation of the anticipatory eyelid movement. Initially, granule cells responded to neutral visual and somatosensory stimuli as well as periorbital airpuffs used for training. As learning progressed, two-thirds of monitored granule cells acquired a conditional response whose timing matched or preceded the learned eyelid movements. Granule cell activity covaried trial by trial to form a redundant code. Many granule cells were also active during movements of nearby body structures. Thus, a predictive signal about the upcoming movement is widely available at the input stage of the cerebellar cortex, as required by forward models of cerebellar control.

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Section: Resultsmentioning

confidence: 99%

Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning

et al. 2017

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“…Graded climbing‐fibre induced calcium signals have also been observed in Purkinje cell dendrites in response to eye‐blink conditioning (Najafi et al . ), which may have implications for short‐ and long‐term plasticity. Indeed, behavioural studies have also shown that, during learning of smooth pursuit eye movements, simple spike activity undergoes trial‐by‐trial depression that is related to the duration of complex spikes (Yang & Lisberger, ).…”

Section: Discussionmentioning

confidence: 99%

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes

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et al. 2016

The Journal of Physiology

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Key points Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes.Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets.The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear.We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number.This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. AbstractPurkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning.

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“…For example, in reaching tasks, complex spike error signals occur in a small fraction of trials and are evident only after extensive averaging [61, 81]. Graded changes in intracellular Ca ++ as well the distribution of response latencies in Purkinje cell dendrites to sensory events provide possible mechanisms for encoding more than binary information in the complex spike discharge [95, 96]. Also, mitigation of the bandwidth problem has been proposed based on the synchrony of the complex spike discharge at the population level.…”

Section: Potential Issues With Error Encoding By Complex Spikesmentioning

confidence: 99%

The Errors of Our Ways: Understanding Error Representations in Cerebellar-Dependent Motor Learning

et al. 2015

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The cerebellum is essential for error-driven motor learning and is strongly implicated in detecting and correcting for motor errors. Therefore, elucidating how motor errors are represented in the cerebellum is essential in understanding cerebellar function, in general, and its role in motor learning, in particular. This review examines how motor errors are encoded in the cerebellar cortex in the context of a forward internal model that generates predictions about the upcoming movement and drives learning and adaptation. In this framework, sensory prediction errors, defined as the discrepancy between the predicted consequences of motor commands and the sensory feedback, are crucial for both on-line movement control and motor learning. While many studies support the dominant view that motor errors are encoded in the complex spike discharge of Purkinje cells, others have failed to relate complex spike activity with errors. Given these limitations, we review recent findings in the monkey showing that complex spike modulation is not necessarily required for motor learning or for simple spike adaptation. Also, new results demonstrate that the simple spike discharge provides continuous error signals that both lead and lag the actual movements in time, suggesting errors are encoded as both an internal prediction of motor commands and the actual sensory feedback. These dual error representations have opposing effects on simple spike discharge, consistent with the signals needed to generate sensory prediction errors used to update a forward internal model.

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Coding of stimulus strength via analog calcium signals in Purkinje cell dendrites of awake mice

Cited by 75 publications

References 93 publications

Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning

Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes

The Errors of Our Ways: Understanding Error Representations in Cerebellar-Dependent Motor Learning

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