Cerebellar Purkinje cells in male macaques combine sensory and motor information to predict the sensory consequences of active self-motion.

Accurate perception and behavior rely on distinguishing sensory signals arising from unexpected events from those originating from our own voluntary actions. In the vestibular system, sensory input that is the consequence of active self-motion is canceled early at the first central stage of processing to ensure postural and perceptual stability. However, the source of the required cancellation signal was unknown. Here, we show that the cerebellum combines sensory and motor-related information to predict the sensory consequences of active self-motion. Recordings during attempted but unrealized head movements in two male rhesus monkeys, revealed that the motor-related signals encoded by anterior vermis Purkinje cells explain their altered sensitivity to active versus passive self-motion. Further, a model combining responses from ~40 Purkinje cells accounted for the cancellation observed in early vestibular pathways. These findings establish how cerebellar Purkinje cells predict sensory outcomes of self-movements, resolving a long-standing issue of sensory signal suppression during self-motion.

Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals.

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

Cerebellum function: The chronometry of social perception.

The posterior cerebellum is emerging as a key structure for social cognition. A new study causally demonstrates its early involvement during emotion perception and functional connectivity with the posterior superior temporal sulcus, a cortical hub of the social brain.

Bimanual coordinated motor skill learning in patients with a chronic cerebellar stroke.

Cerebellar strokes induce coordination disorders that can affect activities of daily living. Evidence-based neurorehabilitation programs are founded on motor learning principles. The cerebellum is a key neural structure in motor learning. It is unknown whether and how well chronic cerebellar stroke individuals (CCSIs) can learn to coordinate their upper limbs through bimanual motor skill learning. The aim was to determine whether CCSIs could achieve bimanual skill learning through a serious game with the REAplan® robot and to compare CCSIs with healthy individuals (HIs). Over three consecutive days, sixteen CCSIs and eighteen HIs were trained on an asymmetric bimanual coordination task ("CIRCUIT" game) with the REAplan® robot, allowing quantification of speed, accuracy and coordination. The primary outcomes were the bimanual speed/accuracy trade-off (BiSAT) and bimanual coordination factor (BiCo). They were also evaluated on a bimanual REACHING task on Days 1 and 3. Correlation analyses between the robotic outcomes and clinical scale scores were computed. Throughout the sessions, BiSAT and BiCo improved during the CIRCUIT task in both HIs and CCSIs. On Day 3, HIs and CCSIs showed generalization of BiSAT, BiCo and transferred to the REACHING task. There was no significant between-group difference in progression. Four CCSIs and two HIs were categorized as "poor learners" according to BiSAT and/or BiCo. Increasing age correlated with reduced BiSAT but not BiCo progression. Over three days of training, HIs and CCSIs improved, retained, generalized and transferred a coordinated bimanual skill. There was no between-group difference, suggesting plastic compensation in CCSIs. Clinical trial NCT04642599 approved the 24th of November 2020.

Dynamic changes in somatosensory and cerebellar activity mediate temporal recalibration of self-touch.

An organism's ability to accurately anticipate the sensations caused by its own actions is crucial for a wide range of behavioral, perceptual, and cognitive functions. Notably, the sensorimotor expectations produced when touching one's own body attenuate such sensations, making them feel weaker and less ticklish and rendering them easily distinguishable from potentially harmful touches of external origin. How the brain learns and keeps these action-related sensory expectations updated is unclear. Here we employ psychophysics and functional magnetic resonance imaging to pinpoint the behavioral and neural substrates of dynamic recalibration of expected temporal delays in self-touch. Our psychophysical results reveal that self-touches are less attenuated after systematic exposure to delayed self-generated touches, while responses in the contralateral somatosensory cortex that normally distinguish between delayed and nondelayed self-generated touches become indistinguishable. During the exposure, the ipsilateral anterior cerebellum shows increased activity, supporting its proposed role in recalibrating sensorimotor predictions. Moreover, responses in the cingulate areas gradually increase, suggesting that as delay adaptation progresses, the nondelayed self-touches trigger activity related to cognitive conflict. Together, our results show that sensorimotor predictions in the simplest act of touching one's own body are upheld by a sophisticated and flexible neural mechanism that maintains them accurate in time.

A chronometric study of the posterior cerebellum's function in emotional processing.

The posterior cerebellum is a recently discovered hub of the affective and social brain, with different subsectors contributing to different social functions. However, very little is known about when the posterior cerebellum plays a critical role in social processing. Due to its location and anatomy, it has been difficult to use traditional approaches to directly study the chronometry of the cerebellum. To address this gap in cerebellar knowledge, here we investigated the causal contribution of the posterior cerebellum to social processing using a chronometric transcranial magnetic stimulation (TMS) approach. We show that the posterior cerebellum is recruited at an early stage of emotional processing (starting from 100 ms after stimulus onset), simultaneously with the posterior superior temporal sulcus (pSTS), a key node of the social brain. Moreover, using a condition-and-perturb TMS approach, we found that the recruitment of the pSTS in emotional processing is dependent on cerebellar activation. Our results are the first to shed light on chronometric aspects of cerebellar function and its causal functional connectivity with other nodes of the social brain.

Developmentally Unique Cerebellar Processing Prioritizes Self- over Other-Generated Movements.

Animals must distinguish the sensory consequences of self-generated movements (reafference) from those of other-generated movements (exafference). Only self-generated movements entail the production of motor copies (i.e., corollary discharges), which are compared with reafference in the cerebellum to compute predictive or internal models of movement. Internal models emerge gradually over the first three postnatal weeks in rats through a process that is not yet fully understood. Previously, we demonstrated in postnatal day (P) 8 and P12 rats that precerebellar nuclei convey corollary discharge and reafference to the cerebellum during active (REM) sleep when pups produce limb twitches. Here, recording from a deep cerebellar nucleus (interpositus, IP) in P12 rats of both sexes, we compared reafferent and exafferent responses with twitches and limb stimulations, respectively. As expected, most IP units showed robust responses to twitches. However, in contrast with other sensory structures throughout the brain, relatively few IP units showed exafferent responses. Upon finding that exafferent responses occurred in pups under urethane anesthesia, we hypothesized that urethane inhibits cerebellar cortical cells, thereby disinhibiting exafferent responses in IP. In support of this hypothesis, ablating cortical tissue dorsal to IP mimicked the effects of urethane on exafference. Finally, the results suggest that twitch-related corollary discharge and reafference are conveyed simultaneously and in parallel to cerebellar cortex and IP. Based on these results, we propose that twitches provide opportunities for the nascent cerebellum to integrate somatotopically organized corollary discharge and reafference, thereby enabling the development of closed-loop circuits and, subsequently, internal models.

Central amygdala contributes to stimulus facilitation and pre-stimulus vigilance during cerebellar learning.

Our previous studies found that the central amygdala (CeA) modulates cerebellum-dependent eyeblink conditioning (EBC) using muscimol inactivation. We also found that CeA inactivation decreases cerebellar neuronal activity during the conditional stimulus (CS) from the start of training. Based on these findings, we hypothesized that the CeA facilitates CS input to the cerebellum. The current study tested the CS facilitation hypothesis using optogenetic inhibition with archaerhodopsin (Arch) and excitation with channelrhodopsin (ChR2) of the CeA during EBC in male rats. Optogenetic manipulations were administered during the 400 ms tone CS or during a 400 ms pre-CS period. As predicted by the CS facilitation hypothesis CeA inhibition during the CS impaired EBC and CeA excitation during the CS facilitated EBC. Unexpectedly, CeA inhibition just prior to the CS also impaired EBC, while CeA excitation during the pre-CS pathway did not facilitate EBC. The results suggest that the CeA contributes to CS facilitation and vigilance during the pre-CS period. These putative functions of the CeA may be mediated through separate output pathways from the CeA to the cerebellum.

Climbing fibers provide essential instructive signals for associative learning.

Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber (CF) inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. In the present study we used cell-type-specific perturbations of various cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning in mice. Our findings reveal that, although optogenetic stimulation of either CFs or Purkinje cells can drive learning under some conditions, even subtle reductions in CF signaling completely block learning to natural stimuli. We conclude that CFs and corresponding Purkinje cell complex spike events provide essential instructive signals for associative cerebellar learning.

Modulation of Neural Spiking in Motor Cortex-Cerebellar Networks during Sleep Spindles.

Sleep spindles appear to play an important role in learning new motor skills. Motor skill learning engages several brain regions with two important areas being the motor cortex (M1) and the cerebellum (CB). However, the neurophysiological processes in these areas during sleep, especially how spindle oscillations affect local and cross-region spiking, are not fully understood. We recorded an activity from the M1 and cerebellar cortex in eight rats during spontaneous activity to investigate how sleep spindles in these regions are related to local spiking as well as cross-region spiking. We found that M1 firing was significantly changed during both M1 and CB spindles, and this spiking occurred at a preferred phase of the spindle. On average, M1 and CB neurons showed most spiking at the M1 or CB spindle peaks. These neurons also developed a preferential phase locking to local or cross-area spindles with the greatest phase-locking value at spindle peaks; however, this preferential phase locking was not significant for cerebellar neurons when compared with CB spindles. Additionally, we found that the percentage of task-modulated cells in the M1 and CB that fired with nonuniform spike phase distribution during M1/CB spindle peaks were greater in the rats that learned a reach-to-grasp motor task robustly. Finally, we found that spindle band LFP coherence (for M1 and CB LFPs) showed a positive correlation with success rate in the motor task. These findings support the idea that sleep spindles in both the M1 and CB recruit neurons that participate in the awake task to support motor memory consolidation.

Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning.

According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidirectional plasticity appears crucial for learning, in which different microzones can undergo opposite changes of synaptic strength (e.g. downbound microzones-more likely depression, upbound microzones-more likely potentiation), and multiple forms of plasticity have been identified, distributed over different cerebellar circuit synapses. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding downbound and upbound modules that are subject to multiple plasticity rules. Simulations indicate that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity at the pf-PC synapses as well as at the synapses of the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both microzones contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC and/or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum can facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution.

Plastic vasomotion entrainment.

The presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel 'shadow' was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy or the deep-brain fiber photometry methods. Vertical stripes horizontally oscillating at a low temporal frequency (0.25 Hz) were presented to the awake mouse, and oscillatory vasomotion locked to the temporal frequency of the visual stimulation was induced not only in the primary visual cortex but across a wide surface area of the cortex and the cerebellum. The visually induced vasomotion adapted to a wide range of stimulation parameters. Repeated trials of the visual stimulus presentations resulted in the plastic entrainment of vasomotion. Horizontally oscillating visual stimulus is known to induce horizontal optokinetic response (HOKR). The amplitude of the eye movement is known to increase with repeated training sessions, and the flocculus region of the cerebellum is known to be essential for this learning to occur. Here, we show a strong correlation between the average HOKR performance gain and the vasomotion entrainment magnitude in the cerebellar flocculus. Therefore, the plasticity of vasomotion and neuronal circuits appeared to occur in parallel. Efficient energy delivery by the entrained vasomotion may contribute to meeting the energy demand for increased coordinated neuronal activity and the subsequent neuronal circuit reorganization.

Neuroprotective Effect of Sterculia setigera Leaves Hydroethanolic Extract.

Plants are a valuable source of information for pharmacological research and new drug discovery. The present study aimed to evaluate the neuroprotective potential of the leaves of the medicinal plant Sterculia setigera. In vitro, the effect of Sterculia setigera leaves dry hydroethanolic extract (SSE) was tested on cultured cerebellar granule neurons (CGN) survival when exposed to hydrogen peroxide (H2O2) or 6-hydroxydopamine (6-OHDA), using the viability probe fluorescein diacetate (FDA), a lactate dehydrogenase (LDH) activity assay, an immunocytochemical staining against Gap 43, and the quantification of the expression of genes involved in apoptosis, necrosis, or oxidative stress. In vivo, the effect of intraperitoneal (ip) injection of SSE was assessed on the developing brain of 8-day-old Wistar rats exposed to ethanol neurotoxicity by measuring caspase-3 activity on cerebellum homogenates, the expression of some genes in tissue extracts, the thickness of cerebellar cortical layers and motor coordination. In vitro, SSE protected CGN against H2O2 and 6-OHDA-induced cell death at a dose of 10 µg/mL, inhibited the expression of genes Casp3 and Bad, and upregulated the expression of Cat and Gpx7. In vivo, SSE significantly blocked the deleterious effect of ethanol by reducing the activity of caspase-3, inhibiting the expression of Bax and Tp53, preventing the reduction of the thickness of the internal granule cell layer of the cerebellar cortex, and restoring motor functions. Sterculia setigera exerts neuroactive functions as claimed by traditional medicine and should be a good candidate for the development of a neuroprotective treatment against neurodegenerative diseases.

The olivary input to the cerebellum dissociates sensory events from movement plans.

Neurons in the inferior olive are thought to anatomically organize the Purkinje cells (P-cells) of the cerebellum into computational modules, but what is computed by each module? Here, we designed a saccade task in marmosets that dissociated sensory events from motor events and then recorded the complex and simple spikes of hundreds of P-cells. We found that when a visual target was presented at a random location, the olive reported the direction of that sensory event to one group of P-cells, but not to a second group. However, just before movement onset, it reported the direction of the planned movement to both groups, even if that movement was not toward the target. At the end of the movement if the subject experienced an error but chose to withhold the corrective movement, only the first group received information about the sensory prediction error. We organized the P-cells based on the information content of their olivary input and found that in the group that received sensory information, the simple spikes were suppressed during fixation, then produced a burst before saccade onset in a direction consistent with assisting the movement. In the second group, the simple spikes were not suppressed during fixation but burst near saccade deceleration in a direction consistent with stopping the movement. Thus, the olive differentiated the P-cells based on whether they would receive sensory or motor information, and this defined their contributions to control of movements as well as holding still.

Detection of Threshold-Level Stimuli Modulated by Temporal Predictions of the Cerebellum.

The cerebellum has the reputation of being a primitive part of the brain that mostly is involved in motor coordination and motor control. Older lesion studies and more recent electrophysiological studies have, however, indicated that it is involved in temporal perception and temporal expectation building. An outstanding question is whether this temporal expectation building cerebellar activity has functional relevance. In this study, we collected magnetoencephalographic data from 30 healthy participants performing a detection task on at-threshold stimulation that was presented at the end of a sequence of temporally regular or irregular above-threshold stimulation. We found that behavioral detection rates depended on the degree of irregularity in the sequence preceding it. We also found cerebellar responses evoked by above-threshold and at-threshold stimulation. The evoked responses to at-threshold stimulation differed significantly, depending on whether it was preceded by a regular or an irregular sequence. Finally, we found that detection performance across participants correlated significantly with the differences in cerebellar evoked responses to the at-threshold stimulation, demonstrating the functional relevance of cerebellar activity in sensory expectation building. We furthermore found evidence of thalamic involvement, as indicated by responses in the beta band (14-30 Hz) and by significant modulations of cerebello-thalamic connectivity by the regularity of the sequence and the kind of stimulation terminating the sequence. These results provide evidence that the temporal expectation building mechanism of the cerebellum, what we and others have called an internal clock, shows functional relevance by regulating behavior and performance in sensory action that requires acting and integrating evidence over precise timescales.

Comparing the effects of cerebellar and prefrontal anodal transcranial direct current stimulation concurrent with postural training on balance and fatigue in patients with multiple sclerosis: a double-blind, randomized, sham-controlled trial.

Fatigue and balance disorders are common challenges experienced by Multiple Sclerosis (MS) individuals. The purpose of this study was to compare the concurrent effects of cerebellar and prefrontal anodal trans-cranial direct current stimulation (a-tDCS) with postural training on balance and fatigue in MS patients. 51 patients were evaluated to randomly allocation to a-tDCS over cerebellum, a-tDCS over dorsolateral prefrontal cortex (DLPFC) and sham group. 46 individuals (n = 16 in experimental groups and n = 14 in control group) followed treatment. All the groups received 10 sessions of postural training. The experimental groups underwent a-tDCS with a current of 1.5 mA for a period of 20 min. While, in the sham group, tDCS was only activated for 30 s and then turned off. The treatment included 10 sessions for four weeks. Before and after intervention, fatigue and balance were assessed using Fatigue Severity Scale (FSS), Timed Up and Go (TUG) test and Berg Balance Score (BBS), respectively. There was found a significant reduction in fatigue in the group receiving a-tDCS over the prefrontal cortex with postural training compared to the other two groups (P < 0.001). Additionally, a significant improvement was found in balance in the group receiving a-tDCS over the cerebellum concurrent with postural training in comparison to the other two groups (P < 0.001). Besides, in the sham group, the significant results were not reported in the variables. (P > 0.001). The results demonstrated that a-tDCS enhances the effects of postural training on balance and fatigue in MS patients.

Posture enhancement with cerebellum transcranial electrical stimulation: a systematic review of current methods and findings.

Recently, transcranial electrical stimulation (tES) has gained increasing popularity among researchers, especially for recovery and improvement, but interpretation of these results is difficult due to variations in study methods and outcome measurements. The main goal of this study was to better understand the postural and balance indicators affected by cerebellar tES, as the cerebellum is the main brain region responsible for controlling balance. For this systematic literature review, three databases were searched for articles where the cerebellum was stimulated by any type of tES in either healthy participants or those with neurologic disorders. Postural, dynamic, and/or static stability measurements were recorded, and risk of bias was assessed on the PEDro scale. A total of 21 studies were included in the analysis. 17 studies reported improvements after application of tES. 14 studies stimulated the cerebellum unilaterally and 15 used this modality for 20 min. Moreover, all studies exclusively used transcranial direct current as the type of stimulation. Evaluation of PEDro results showed that studies included in the analysis utilized good methodology. Although there were some inconsistencies in study results, overall, it was demonstrated that tES can improve balance and postural index under both healthy and neurological conditions. Further research of bilateral cerebellar stimulation or the use of transcranial alternating current stimulation, transcranial random noise stimulation, and transcranial pulsed current stimulation is needed for a more comprehensive assessment of the potential positive effects of cerebellar tES on the balance system.

Excitatory cerebellar transcranial direct current stimulation boosts the leverage of prior knowledge for predicting actions.

The cerebellum causally supports social processing by generating internal models of social events based on statistical learning of behavioral regularities. However, whether the cerebellum is only involved in forming or also in using internal models for the prediction of forthcoming actions is still unclear. We used cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of healthy adults in using previously learned expectations in an action prediction task. In a first learning phase of this task, participants were exposed to different levels of associations between specific actions and contextual elements, to induce the formation of either strongly or moderately informative expectations. In a following testing phase, which assessed the use of these expectations for predicting ambiguous (i.e. temporally occluded) actions, we delivered ctDCS. Results showed that anodic, compared to sham, ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. Since ctDCS was delivered during the testing phase, that is after expectations were established, our findings suggest that the cerebellum is causally involved in using internal models (and not just in generating them). This encourages the exploration of the clinical effects of ctDCS to compensate poor use of predictive internal models for social perception.

Kit Ligand and Kit receptor tyrosine kinase sustain synaptic inhibition of Purkinje cells.

The cell-type-specific expression of ligand/receptor and cell-adhesion molecules is a fundamental mechanism through which neurons regulate connectivity. Here, we determine a functional relevance of the long-established mutually exclusive expression of the receptor tyrosine kinase Kit and the trans-membrane protein Kit Ligand by discrete populations of neurons in the mammalian brain. Kit is enriched in molecular layer interneurons (MLIs) of the cerebellar cortex (i.e., stellate and basket cells), while cerebellar Kit Ligand is selectively expressed by a target of their inhibition, Purkinje cells (PCs). By in vivo genetic manipulation spanning embryonic development through adulthood, we demonstrate that PC Kit Ligand and MLI Kit are required for, and capable of driving changes in, the inhibition of PCs. Collectively, these works in mice demonstrate that the Kit Ligand/Kit receptor dyad sustains mammalian central synapse function and suggest a rationale for the affiliation of Kit mutation with neurodevelopmental disorders.

Etomidate enhances cerebellar CF-PC synaptic plasticity through CB1 receptor/PKA cascade in vitro in mice.

Etomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM). Blockade of mGluR1 receptor with JNJ16259685, ET triggered the tetanic stimulation to induce a CF-PC LTD accompanied with an increase in paired-pulse ratio (PPR). The ET-triggered CF-PC LTD was abolished by extracellular administration of an N-methyl-(D)-aspartate (NMDA) receptor antagonist, D-APV, as well as by intracellular blockade of NMDA receptors activity with MK801. Furthermore, blocking cannabinoids 1 (CB1) receptor with AM251 or chelating intracellular Ca2+ with BAPTA, ET failed to trigger the CF-PC LTD. Moreover, the ET-triggered CF-PC LTD was abolished by inhibition of protein kinase A (PKA), but not by inhibition of protein kinase C inhibiter. The present results suggest that ET acts on postsynaptic NMDA receptor resulting in an enhancement of the cerebellar CF-PC LTD through CB1 receptor/PKA cascade in vitro in mice. These results provide new evidence and possible mechanism for ET anesthesia to affect motor learning and motor coordination by regulating cerebellar CF-PC LTD.