Climbing Fiber Activity Research Articles

Cerebellar climbing fibers signal flexible, rapidly adapting reward predictions.

Classical models of cerebellar computation posit that climbing fibers (CFs) operate according to supervised learning rules, correcting movements by signaling the occurrence of motor errors. However, recent findings suggest that in some behaviors, CF activity can exhibit features that resemble the instructional signals necessary for reinforcement learning, namely reward prediction errors (rPEs). Despite these initial observations, many key properties of reward-related CF responses remain unclear, thus limiting our understanding of how they operate to guide cerebellar learning. Here, we have measured the postsynaptic responses of CFs onto cerebellar Purkinje cells using two-photon calcium imaging to test how they respond to learned stimuli that either do or do not predict reward. We find that CFs can develop generalized responses to similar cues of the same modality, regardless of whether they are reward predictive. However, this generalization depends on temporal context, and does not extend across sensory modalities. Further, learned CF responses are flexible, and can be rapidly updated according to new reward contingencies. Together these results suggest that CFs can generate learned, reward-predictive responses that flexibly adapt to the current environment in a context-sensitive manner.

Reward-driven cerebellar climbing fiber activity influences both neural and behavioral learning.

The cerebellum plays a key role in motor coordination and learning. In contrast with classical supervised learning models, recent work has revealed that CFs can signal reward-predictive information in some behaviors. This raises the question of whether CFs may also operate according to principles similar to those described by reinforcement learning models. To test how CFs operate during reward-guided behavior, and evaluate the role of reward-related CF activity in learning, we have measured CF responses in Purkinje cells of the lateral cerebellum during a Pavlovian task using 2-photon calcium imaging. Specifically, we have performed multi-stimulus experiments to determine whether CF activity meets the requirements of a reward prediction error (rPE) signal for transfer from an unexpected reward to a reward-predictive cue. We find that once CF activity is transferred to a conditioned stimulus, and there is no longer a response to reward, CFs cannot generate learned responses to a second conditioned stimulus that carries the same reward prediction. In addition, by expressing the inhibitory opsin GtACR2 in neurons of the inferior olive, and optically inhibiting these neurons across behavioral training at the time of unexpected reward, we find that the transfer of CF signals to the conditioned stimulus is impaired. Moreover, this optogenetic inhibition also impairs learning, resulting in a deficit in anticipatory lick timing. Together, these results indicate that CF signals can exhibit several characteristics in common with rPEs during reinforcement learning, and that the cerebellum can harness these learning signals to generate accurately timed motor behavior.

Climbing Fiber Activation Induced by Footshock in the Cerebellar Vermis Lobule IV/V of Freely Moving Mice.

Parallel fibers (PFs) in the cerebellar cortex are involved in a series of coordinated responses in the fear conditioning paradigm induced by footshock. However, whether footshock can activate cerebellar climbing fibers (CFs) remains unclear. In this study, we recorded calcium (Ca2+) activity in CFs by optical fiber photometry in the cerebellar vermis lobule IV/V of freely moving mice with footshock stimulation. We found that the activation of CFs in the lobule IV/V was highly correlated with footshock stimulation but not with the sound stimulation used as a control. This result suggests that afferent information from CFs might be associated with the motor initiation of fear-related behaviors or fear emotion itself. Thus, our results suggest that a characteristic CF signal in the cerebellar cortex might be related to fear processing or footshock-related behaviors (such as startle responses or pain sensation).

C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity

Changes in neural activity induced by learning and novel environments have been reported to lead to the formation of new synapses in the adult brain. However, the underlying molecular mechanism is not well understood. Here, we show that Purkinje cells (PCs), which have established adult-type monosynaptic innervation by climbing fibers (CFs) after elimination of weak CFs during development, can be reinnervated by multiple CFs by increased expression of the synaptic organizer C1ql1 in CFs or Bai3, a receptor for C1ql1, in PCs. In the adult cerebellum, CFs are known to have transverse branches that run in a mediolateral direction without forming synapses with PCs. Electrophysiological, Ca2+-imaging and immunohistochemical studies showed that overexpression of C1ql1 or Bai3 caused these CF transverse branches to elongate and synapse on the distal dendrites of mature PCs. Mature PCs were also reinnervated by multiple CFs when the glutamate receptor GluD2, which is essential for the maintenance of synapses between granule cells and PCs, was deleted. Interestingly, the effect of GluD2 knockout was not observed in Bai3 knockout PCs. In addition, C1ql1 levels were significantly upregulated in CFs of GluD2 knockout mice, suggesting that endogenous, not overexpressed, C1ql1-Bai3 signaling could regulate the reinnervation of mature PCs by CFs. Furthermore, the effects of C1ql1 and Bai3 overexpression required neuronal activity in the PC and CF, respectively. C1ql1 immunoreactivity at CF-PC synapses was reduced when the neuronal activity of CFs was suppressed. These results suggest that C1ql1-Bai3 signaling may mediate CF synaptogenesis in mature PCs, potentially in concert with neuronal activity.

Diversity of cellular physiology and morphology of Purkinje cells in the adult zebrafish cerebellum.

This study was designed to explore the functional circuitry of the adult zebrafish cerebellum, focusing on its Purkinje cells and using whole-cell patch recordings and single cell labeling in slice preparations. Following physiological characterizations, the recorded single cells were labeled for morphological identification. It was found that the zebrafish Purkinje cells are surprisingly diverse. Based on their physiology and morphology, they can be classified into at least three subtypes: Type I, a narrow spike cell, which fires only narrow Na+ spikes (<3ms in duration), and has a single primary dendrite with an arbor restricted to the distal molecular layer; Type II, a broad spike cell, which fires broad Ca2+ spikes (5-7ms in duration) and has a primary dendrite with limited branching in the inner molecular layer and then further radiates throughout the molecular layer; and Type III, a very broad spike cell, which fires very broad Ca2+ spikes (≥10ms in duration) and has a dense proximal dendritic arbor that is either restricted to the inner molecular layer (Type IIIa), or radiates throughout the entire molecular layer (Type IIIb). The graded paired-pulse facilitation of these Purkinje cells' responses to parallel fiber activations and the all-or-none, paired-pulse depression of climbing fiber activation are largely similar to those reported for mammals. The labeled axon terminals of these Purkinje cells end locally, as reported for larval zebrafish. The present study provides evidence that the corresponding functional circuitry and information processing differ from what has been well-established in the mammalian cerebellum.

Optical Fiber-Based Recording of Climbing Fiber Ca2+ Signals in Freely Behaving Mice.

Simple SummaryIn this study, we established a robust and accessible method to chronically record calcium signals from climbing fiber (CF) projections to the cerebellar cortex in freely behaving mice. This technique was demonstrated with optical fiber photometry in lobule IV/V of the cerebellar vermis during open field exploration, where various movement-evoked CF Ca2+ signals were observed, and the onset of exploratory-like behaviors was highly synchronous with the recorded CF activity.The olivocerebellar circuitry is important to convey both motor and non-motor information from the inferior olive (IO) to the cerebellar cortex. Several methods are currently established to observe the dynamics of the olivocerebellar circuitry, largely by recording the complex spike activity of cerebellar Purkinje cells; however, these techniques can be technically challenging to apply in vivo and are not always possible in freely behaving animals. Here, we developed a method for the direct, accessible, and robust recording of climbing fiber (CF) Ca2+ signals based on optical fiber photometry. We first verified the IO stereotactic coordinates and the organization of contralateral CF projections using tracing techniques and then injected Ca2+ indicators optimized for axonal labeling, followed by optical fiber-based recordings. We demonstrated this method by recording CF Ca2+ signals in lobule IV/V of the cerebellar vermis, comparing the resulting signals in freely moving mice. We found various movement-evoked CF Ca2+ signals, but the onset of exploratory-like behaviors, including rearing and tiptoe standing, was highly synchronous with recorded CF activity. Thus, we have successfully established a robust and accessible method to record the CF Ca2+ signals in freely behaving mice, which will extend the toolbox for studying cerebellar function and related disorders.

Associative anticipatory learning and control of the cerebellar cortex based on the spike-timing-dependent plasticity of the parallel fiber-Purkinje cell synapses

Time delays are inevitable in the neural processing of sensorimotor systems; small delays can cause severe damage to movement accuracy and stability. It is strongly suggested that the cerebellum compensates for delays in neural signal processing and performs predictive control. Neural computational theories have explored concepts of the internal models of control objects—believed to avoid delays by providing internal feedback information—although there has been no clear relevance to neural processing. The timing-dependent plasticity of parallel fiber-Purkinje cell synapses is well known. The long-term depression of the synapse is observed when parallel fiber activation precedes climbing fiber activation within −50–300 ms, and is the greatest within 50–200 ms. This paper presents a theory that this temporal difference of 50–200 ms is the basis for an associative anticipation of as many milliseconds. Associative learning can theoretically connect an input signal to a desired signal; therefore, a 50–200 ms earlier input signal can be connected to a desired output signal through temporary asymmetric plasticity. After learning is completed, an input signal generates a desired output signal that appears 50–200 ms later. For the associative learning of temporally continuous signals, this study integrates the universal function approximation capability of the cerebellar cortex model and temporally asymmetric synaptic plasticity to create the theory of associative anticipatory learning of the cerebellum. The effective motor control of this learning is demonstrated by adaptively stabilizing an inverted pendulum with a delay similar to that done by humans.

Cerebellar climbing fibers encode expected reward size.

Climbing fiber inputs to the cerebellum encode error signals that instruct learning. Recently, evidence has accumulated to suggest that the cerebellum is also involved in the processing of reward. To study how rewarding events are encoded, we recorded the activity of climbing fibers when monkeys were engaged in an eye movement task. At the beginning of each trial, the monkeys were cued to the size of the reward that would be delivered upon successful completion of the trial. Climbing fiber activity increased when the monkeys were presented with a cue indicating a large reward, but not a small reward. Reward size did not modulate activity at reward delivery or during eye movements. Comparison between climbing fiber and simple spike activity indicated different interactions for coding of movement and reward. These results indicate that climbing fibers encode the expected reward size and suggest a general role of the cerebellum in associative learning beyond error correction.

The role of the cerebellum in adaptation: ALE meta-analyses on sensory feedback error.

It is widely accepted that unexpected sensory consequences of self‐action engage the cerebellum. However, we currently lack consensus on where in the cerebellum, we find fine‐grained differentiation to unexpected sensory feedback. This may result from methodological diversity in task‐based human neuroimaging studies that experimentally alter the quality of self‐generated sensory feedback. We gathered existing studies that manipulated sensory feedback using a variety of methodological approaches and performed activation likelihood estimation (ALE) meta‐analyses. Only half of these studies reported cerebellar activation with considerable variation in spatial location. Consequently, ALE analyses did not reveal significantly increased likelihood of activation in the cerebellum despite the broad scientific consensus of the cerebellum's involvement. In light of the high degree of methodological variability in published studies, we tested for statistical dependence between methodological factors that varied across the published studies. Experiments that elicited an adaptive response to continuously altered sensory feedback more frequently reported activation in the cerebellum than those experiments that did not induce adaptation. These findings may explain the surprisingly low rate of significant cerebellar activation across brain imaging studies investigating unexpected sensory feedback. Furthermore, limitations of functional magnetic resonance imaging to probe the cerebellum could play a role as climbing fiber activity associated with feedback error processing may not be captured by it. We provide methodological recommendations that may guide future studies.

Neurons of the inferior olive respond to broad classes of sensory input while subject to homeostatic control.

Key points Purkinje cells in the cerebellum integrate input from sensory organs with that from premotor centres.Purkinje cells use a variety of sensory inputs relaying information from the environment to modify motor control.Here we investigated to what extent the climbing fibre inputs to Purkinje cells signal mono‐ or multi‐sensory information, and to what extent this signalling is subject to recent history of activity.We show that individual climbing fibres convey multiple types of sensory information, together providing a rich mosaic projection pattern of sensory signals across the cerebellar cortex.Moreover, firing probability of climbing fibres following sensory stimulation depends strongly on the recent history of activity, showing a tendency to homeostatic dampening. Cerebellar Purkinje cells integrate sensory information with motor efference copies to adapt movements to behavioural and environmental requirements. They produce complex spikes that are triggered by the activity of climbing fibres originating in neurons of the inferior olive. These complex spikes can shape the onset, amplitude and direction of movements and the adaptation of such movements to sensory feedback. Clusters of nearby inferior olive neurons project to parasagittally aligned stripes of Purkinje cells, referred to as ‘microzones’. It is currently unclear to what extent individual Purkinje cells within a single microzone integrate climbing fibre inputs from multiple sources of different sensory origins, and to what extent sensory‐evoked climbing fibre responses depend on the strength and recent history of activation. Here we imaged complex spike responses in cerebellar lobule crus 1 to various types of sensory stimulation in awake mice. We find that different sensory modalities and receptive fields have a mild, but consistent, tendency to converge on individual Purkinje cells, with climbing fibres showing some degree of input‐specificity. Purkinje cells encoding the same stimulus show increased events with coherent complex spike firing and tend to lie close together. Moreover, whereas complex spike firing is only mildly affected by variations in stimulus strength, it depends strongly on the recent history of climbing fibre activity. Our data point towards a mechanism in the olivo‐cerebellar system that regulates complex spike firing during mono‐ or multi‐sensory stimulation around a relatively low set‐point, highlighting an integrative coding scheme of complex spike firing under homeostatic control.

Conversion of Graded Presynaptic Climbing Fiber Activity into Graded Postsynaptic Ca2+ Signals by Purkinje Cell Dendrites

The brain must make sense of external stimuli to generate relevant behavior. We used a combination of invivo approaches to investigate how the cerebellum processes sensory-related information. We found that the inferior olive encodes contexts of sensory-associated external cues in a graded manner, apparent in the presynaptic activity of their axonal projections (climbing fibers) in the cerebellar cortex. Individual climbing fibers were broadly responsive to different sensory modalities but relayed sensory-related information to the cortex in a lobule-dependent manner. Purkinje cell dendrites faithfully transformed this climbing fiber activity into dendrite-wide Ca2+ signals without a direct contribution from the mossy fiber pathway. These results demonstrate that the size of climbing-fiber-evoked Ca2+ signals in Purkinje cell dendrites is largely determined by the firing level of climbing fibers. This coding scheme emphasizes the overwhelming role of the inferior olive in generating salient signals useful for instructing plasticity and learning.

Coordinated cerebellar climbing fiber activity signals learned sensorimotor predictions.

The prevailing model of cerebellar learning states that climbing fibers (CFs) are both driven by, and serve to correct, erroneous motor output. However, this model is grounded largely in studies of behaviors that utilize hardwired neural pathways to link sensory input to motor output. To test whether this model applies to more flexible learning regimes that require arbitrary sensorimotor associations, we developed a cerebellar-dependent motor learning task that is compatible with both mesoscale and single-dendrite-resolution calcium imaging in mice. We found that CFs were preferentially driven by and more time-locked to correctly executed movements and other task parameters that predict reward outcome, exhibiting widespread correlated activity in parasagittal processing zones that was governed by these predictions. Together, our data suggest that such CF activity patterns are well-suited to drive learning by providing predictive instructional input that is consistent with an unsigned reinforcement learning signal but does not rely exclusively on motor errors.

Synchronicity and Rhythmicity of Purkinje Cell Firing during Generalized Spike-and-Wave Discharges in a Natural Mouse Model of Absence Epilepsy.

Absence epilepsy is characterized by the occurrence of generalized spike and wave discharges (GSWDs) in electrocorticographical (ECoG) recordings representing oscillatory activity in thalamocortical networks. The oscillatory nature of GSWDs has been shown to be reflected in the simple spike activity of cerebellar Purkinje cells and in the activity of their target neurons in the cerebellar nuclei, but it is unclear to what extent complex spike activity is implicated in generalized epilepsy. Purkinje cell complex spike firing is elicited by climbing fiber activation and reflects action potential firing in the inferior olive. Here, we investigated to what extent modulation of complex spike firing is reflected in the temporal patterns of seizures. Extracellular single-unit recordings in awake, head-restrained homozygous tottering mice, which suffer from a mutation in the voltage-gated CaV2.1 calcium channel, revealed that a substantial proportion of Purkinje cells (26%) showed increased complex spike activity and rhythmicity during GSWDs. Moreover, Purkinje cells, recorded either electrophysiologically or by using Ca2+-imaging, showed a significant increase in complex spike synchronicity for both adjacent and remote Purkinje cells during ictal events. These seizure-related changes in firing frequency, rhythmicity and synchronicity were most prominent in the lateral cerebellum, a region known to receive cerebral input via the inferior olive. These data indicate profound and widespread changes in olivary firing that are most likely induced by seizure-related activity changes in the thalamocortical network, thereby highlighting the possibility that olivary neurons can compensate for pathological brain-state changes by dampening oscillations.

Impaired Motor Coordination and Learning in Mice Lacking Anoctamin 2 Calcium-Gated Chloride Channels

Neurons communicate through excitatory and inhibitory synapses. Both lines of communication are adjustable and allow the fine tuning of signal exchange required for learning processes in neural networks. Several distinct modes of plasticity modulate glutamatergic and GABAergic synapses in Purkinje cells of the cerebellar cortex to promote motor control and learning. In the present paper, we present evidence for a role of short-term ionic plasticity in the cerebellar circuit activity. This type of plasticity results from altered chloride driving forces at the synapses that molecular layer interneurons form on Purkinje cell dendrites. Previous studies have provided evidence for transiently diminished chloride gradients at these GABAergic synapses following climbing fiber activity. Electrical stimulation of climbing fibers in acute slices caused a decline of inhibitory postsynaptic currents recorded from Purkinje cells. Dendritic calcium-gated chloride channels of the type anoctamin 2 (ANO2) were proposed to mediate this short-term modulation of inhibition, but the significance of this process for motor control has not been established yet. Here, we report results of behavioral studies obtained from Ano2−/− mice, a mouse line that was previously shown to lack this particular mode of ionic plasticity. The animals display motor coordination deficits that constitute a condition of mild ataxia. Moreover, motor learning is severely impaired in Ano2−/− mice, suggesting cerebellar dysfunction. This reduced motor performance of Ano2−/− mice highlights the significance of inhibitory control for cerebellar function and introduces calcium-dependent short-term ionic plasticity as an efficient control mechanism for neural inhibition.

Climbing Fiber Regulation of Spontaneous Purkinje Cell Activity and Cerebellum-Dependent Blink Responses(1,2,3).

It has been known for a long time that GABAergic Purkinje cells in the cerebellar cortex, as well as their target neurons in the cerebellar nuclei, are spontaneously active. The cerebellar output will, therefore, depend on how input is integrated into this spontaneous activity. It has been shown that input from climbing fibers originating in the inferior olive controls the spontaneous activity in Purkinje cells. While blocking climbing fiber input to the Purkinje cells causes a dramatic increase in the firing rate, increased climbing fiber activity results in reduced Purkinje cell activity. However, the exact calibration of this regulation has not been examined systematically. Here we examine the relation between climbing fiber stimulation frequency and Purkinje cell activity in unanesthetized decerebrated ferrets. The results revealed a gradual suppression of Purkinje cell activity, starting at climbing fiber stimulation frequencies as low as 0.5 Hz. At 4 Hz, Purkinje cells were completely silenced. This effect lasted an average of 2 min after the stimulation rate was reduced to a lower level. We also examined the effect of sustained climbing fiber stimulation on overt behavior. Specifically, we analyzed conditioned blink responses, which are known to be dependent on the cerebellum, while stimulating the climbing fibers at different frequencies. In accordance with the neurophysiological data, the conditioned blink responses were suppressed at stimulation frequencies of ≥4 Hz.

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

Climbing fiber inputs to Purkinje cells are thought to play a teaching role by generating the instructive signals that drive cerebellar learning. To investigate how these instructive signals are encoded, we recorded the activity of individual climbing fibers during cerebellar-dependent eyeblink conditioning in mice. Our findings show that climbing fibers signal both the unexpected delivery and the unexpected omission of the periocular airpuff that serves as the instructive signal for eyeblink conditioning. In addition, we report the surprising discovery that climbing fibers activated by periocular airpuffs also respond to stimuli from other sensory modalities, if those stimuli are novel or if they predict that the periocular airpuff is about to be presented. This pattern of climbing fiber activity is strikingly similar to the responses of dopamine neurons during reinforcement learning, which have been shown to encode a particular type of instructive signal known as a temporal difference prediction error.

Rapid development of Purkinje cell excitability, functional cerebellar circuit, and afferent sensory input to cerebellum in zebrafish.

The zebrafish has significant advantages for studying the morphological development of the brain. However, little is known about the functional development of the zebrafish brain. We used patch clamp electrophysiology in live animals to investigate the emergence of excitability in cerebellar Purkinje cells, functional maturation of the cerebellar circuit, and establishment of sensory input to the cerebellum. Purkinje cells are born at 3 days post-fertilization (dpf). By 4 dpf, Purkinje cells spontaneously fired action potentials in an irregular pattern. By 5 dpf, the frequency and regularity of tonic firing had increased significantly and most cells fired complex spikes in response to climbing fiber activation. Our data suggest that, as in mammals, Purkinje cells are initially innervated by multiple climbing fibers that are winnowed to a single input. To probe the development of functional sensory input to the cerebellum, we investigated the response of Purkinje cells to a visual stimulus consisting of a rapid change in light intensity. At 4 dpf, sudden darkness increased the rate of tonic firing, suggesting that afferent pathways carrying visual information are already active by this stage. By 5 dpf, visual stimuli also activated climbing fibers, increasing the frequency of complex spiking. Our results indicate that the electrical properties of zebrafish and mammalian Purkinje cells are highly conserved and suggest that the same ion channels, Nav1.6 and Kv3.3, underlie spontaneous pacemaking activity. Interestingly, functional development of the cerebellum is temporally correlated with the emergence of complex, visually-guided behaviors such as prey capture. Because of the rapid formation of an electrically-active cerebellum, optical transparency, and ease of genetic manipulation, the zebrafish has great potential for functionally mapping cerebellar afferent and efferent pathways and for investigating cerebellar control of motor behavior.

Long-term climbing fibre activity induces transcription of microRNAs in cerebellar Purkinje cells.

Synaptic activation of central neurons is often evoked by electrical stimulation leading to post-tetanic potentiation, long-term potentiation or long-term depression. Even a brief electrical tetanus can induce changes in as many as 100 proteins. Since climbing fibre activity is often associated with cerebellar behavioural plasticity, we used horizontal optokinetic stimulation (HOKS) to naturally increase synaptic input to floccular Purkinje cells in mice for hours, not minutes, and investigated how this activity influenced the transcription of microRNAs, small non-coding nucleotides that reduce transcripts of multiple, complementary mRNAs. A single microRNA can reduce the translation of as many as 30 proteins. HOKS evoked increases in 12 microRNA transcripts in floccular Purkinje cells. One of these microRNAs, miR335, increased 18-fold after 24 h of HOKS. After HOKS stopped, miR335 transcripts decayed with a time constant of approximately 2.5 h. HOKS evoked a 28-fold increase in pri-miR335 transcripts compared with an 18-fold increase in mature miR335 transcripts, confirming that climbing fibre-evoked increases in miR335 could be attributed to increases in transcription. We used three screens to identify potential mRNA targets for miR335 transcripts: (i) nucleotide complementarity, (ii) detection of increased mRNAs following microinjection of miR335 inhibitors into the cerebellum, and (iii) detection of decreased mRNAs following HOKS. Two genes, calbindin and 14-3-3-θ, passed these screens. Transfection of N2a cells with miR335 inhibitors or precursors inversely regulated 14-3-3-θ transcripts. Immunoprecipitation of 14-3-3-θ co-immunoprecipitated PKC-γ and GABAAγ2. Knockdown of either 14-3-3-θ or PKC-γ decreased the serine phosphorylation of GABAAγ2, suggesting that 14-3-3-θ and PKC-γ under the control of miR335 homeostatically regulate the phosphorylation and insertion of GABAAγ2 into the Purkinje cell post-synaptic membrane.

Sensory processing and corollary discharge effects in posterior caudal lobe Purkinje cells in a weakly electric mormyrid fish.

Although it has been suggested that the cerebellum functions to predict the sensory consequences of motor commands, how such predictions are implemented in cerebellar circuitry remains largely unknown. A detailed and relatively complete account of predictive mechanisms has emerged from studies of cerebellum-like sensory structures in fish, suggesting that comparisons of the cerebellum and cerebellum-like structures may be useful. Here we characterize electrophysiological response properties of Purkinje cells in a region of the cerebellum proper of weakly electric mormyrid fish, the posterior caudal lobe (LCp), which receives the same mossy fiber inputs and projects to the same target structures as the electrosensory lobe (ELL), a well-studied cerebellum-like structure. We describe patterns of simple spike and climbing fiber activation in LCp Purkinje cells in response to motor corollary discharge, electrosensory, and proprioceptive inputs and provide evidence for two functionally distinct Purkinje cell subtypes within LCp. Protocols that induce rapid associative plasticity in ELL fail to induce plasticity in LCp, suggesting differences in the adaptive functions of the two structures. Similarities and differences between LCp and ELL are discussed in light of these results.

Gating of neural error signals during motor learning.

Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors. DOI: http://dx.doi.org/10.7554/eLife.02076.001.