The role of the cerebellum as a comparator of desired motor output and actual performance may be most important during learning of a novel motor task, when movement errors are common and corrective movements are produced to compensate for them. It is suggested that PET and recent fMRI data are compatible with such an interpretation. Increased activity in motor cortical areas during motor learning indicates that these areas also contribute to the learning process, [THACH]

We argue that the function of the cerebellum is more than just an error-detecting mechanism. Rather, the cerebellum plays an important role in all movements. The bias in (re)calibration is an unfortunate restrictive result of a very successful and important experiment, [SMITH, THACH]

Information for motor learning is likely to be stored by groups of Purkinje cells in the cerebellum as suggested by HOUK et al., though their proposal that Purkinje cells act as bistable elements is open to question. THACH's excellent article breaks new ground on what type of information the cerebellum may store. I have queries on whether the cerebellum can generate “thought” or is likely to engage in the purely mental learning of movements, [HOUK et al.; THACH]

To examine the model of the biological motor control proposed by A. Smith, this commentary briefly introduces some result of stiffness measurements during multi-joint arm movements, and, in the light of these results, discusses how likely it is that stiffness is a control parameter and that the cerebellum solely codes the stiffness, [SMITH]

This commentary reviews the case of a patient who could alter the coordination of her prehensile movements when removal of visual feedback reduced her kinetic tremor, but could not coordinate her hand aperture with her hand transport within a single movement. This suggests a dissociation between different subtypes of cerebellar context-response linkage, rather than a single, general association function, [THACH]

Motor learning can be divided into adaptation and skill learning. The cerebellum plays the major role in adaptation learning, which can be described as context-response linkage. Motor skill learning is development of a new ability such as a sequence of motor actions. Skill learning can occur in patients with cerebellar lesions. Cortical mechanisms play a major role in development of skills, [THACH]

Strong stimulation of parallel fibers (PFs) leads to localized calcium influx and a long-term depression (LTD) of PF responses at the site of stimulation. These same stimuli also induce depression at spatially distant synapses to the same cell that is mediated by the diffusible messenger nitric oxide (NO). The demonstration of two distinct forms of LTD provide an explanation for the absence of the NO/cGMP pathway in cultured cells, [CBÉPEL et al.; LINDEN; VINCENT]

It is argued that large-scale neural network simulations of cerebellar cortex and nuclei, based on realistic compartmental models of me major cell populations, are necessary before the problem of motor learning in the cerebellum can be solved, [HOUK et al.; SIMPSON et al.]

Houk et al. suggest that excitatory output from the cerebellar nuclei is fed back into the cerebellum, thus generating a prolonged activity in the cerebellar nuclei which is then molded by inhibitory Purkinje cells. Recent evidence, however, shows that a temporary break in this loop causes a pause in a conditioned eyeblink response, but does not terminate it. [HOUK et al.]

Recent studies have demonstrated that a Purkinje cell specific ionotropic glutamate receptor δ2 subunit is involved in long-term depression (LTD). Identification of molecules involved in LTD has led to the production of mutant mice defective in LTD, motor control, and motor learning. There are disagreements about whether or not and how nitric oxide (NO) is involved in LTD. [CRÉPEL et al.; LINDEN; VINCENT]

Theories of cerebellar arm function should be able to explain the now well-characterized disorders that occur during cerebellar dysfunction in fast arm movements made at single joints. Contrary to claims in Smith's target article, cocontraction is not one of these disorders. Although loss of the joint stiffness function proposed by Smith is consistent with some findings, it does not explain all of these disorders, and therefore gives only a limited view of cerebellar function, [SMITH]

The data on the cellular mechanism of LTD that is presented in four target articles is synthesized into a new model of Purkinje cell plasticity. This model attempts to address credit assignment problems that are crucial in learning systems. Intracellular signal transduction mechanisms may provide the mechanism for a 3-factor learning rule and a trace mechanism. The latter may permit delayed information about motor error to modify the prior synaptic events that caused the error. This model may help to focus future cellular studies on issues that are particularly critical for a computationally viable concept of cerebellar plasticity, [CRÉPEL et al.; HOUK et al.; KANO; LINDEN; VINCENT]

In 1994 and 1995, several new reports appeared regarding cellular mechanisms of LTD. These concern (1) involvement of mGluRl, (2) involvement of glutamate receptor δ2 subunit (GluRδ2), (3) involvement of Ca2+ release from intracellular stores, and (4) origin of nitric oxide (NO). I would like to add these new results to the review article by Crépel et al. [CRÉPEL et al.]

Recent advanced statistical analysis of complex spikes has revealed that their instantaneous firing rate within a time bin of a few milliseconds carries information if many trials are averaged, as happens in motor learning. The firing rate encodes sensory error signals in the inverse-dynamics motor-command coordinates, and these are exactly the same coordinates as for simple spikes. This strongly supports the most critical assumption of the feedback-error-learning model and argues against several hypotheses about the functions of the complex spikes. [HOUK et al.; SIMPSON et al.; SMITH; THACH]

Vincent proposes that the extracellular cGMP found in cerebellum after glutamate receptor activation is released mainly from Purkinje cells because in these neurons the presence of guanylate cyclase has been shown using monoclonal antibodies. It is uncertain, however, whether Purkinje cells are the only source of extracellular cGMP in the cerebellum. This commentary examines the possibility that glial and cerebellar granule cells may also participate in cGMP synthesis and release, Moreover, the hypothesis of transcellular metabolism of citrulline and arginine is discussed. [VINCENT]

We criticize the synaptic theory of long-term memory and the inappropriate usage of physical notions such as “joint stiffness” in motor control theories. Motor control and motor memory hypotheses should be based on explicitly specified hypothetical control variables that are sound from both physiological and physical perspectives. [HOUK et al.; SMITH; THACH]

We suggest that the cerebellum generates sensory or “state” estimates based on outgoing motor commands and sensory feedback. Thus, it is not a motor pattern generator (HOUK et al.) but a predictive system which is intimately involved in motor behavior. This theory may explain the sensitivity of the climbing fibers to both unexpected external events and motor errors (SIMPSON et al.), and we speculate that unusual biophysical properties of the inferior olive might allow the cerebellum to develop multiple asynchronous sensory estimates, [HOUK et al.; SIMPSON et al.; THACH]

In addition to SNP and SIN-1, SNAP suppresses AMPA responses. This suppression is antagonized by carboxy-PTIO in cultured chick cerebellar Purkinje neurons. Intracellular application of cGMP shows a long-lasting suppression of AMPA responses mimicking the cerebellar LTD. These recent results demonstrate that NO can induce LTD-like suppression of AMPA responses and intracellular cGMP and cGMP-dependent protein kinase participate in this suppression. [CRÉPEL et al.; LINDEN; VINCENT]

The involvement of nitric oxide in cerebellar long-term depression is supported by the observation that nitric oxide is released by climbing fiber stimulation and by pharmacological tool usage. Two forms of long-term depression – one depending on large calcium increase and another on nitric oxide – should be distinguished by their physiological relevance. [CRÉPEL et al.; LINDEN; VINCENT]