Thach's target article presents a remarkable overview and integration of animal and human studies on the functions of the cerebellum and makes clear theoretical predictions for both the normal operation of the cerebellum and for the effects of cerebellar lesions in the mature human. Commentary is provided on three areas, namely, spatial navigation, implicit learning, and cerebellar agenesis to elicit further development of the themes already present in Thach's paper, [THACH]

The views of Houk et al., Smith, and Thach on the role of cerebellum in movement control differ substantially, but all three are flawed by the false reasoning that because information passes from the cerebellum to movements the cerebellum must be a movement controller, or a part of one. The divergent and less than compelling ideas expressed by these leading cerebellar theorists epitomize the fruitlessness of this paradigm, and signal the need for a change. [HOUK et al.; SMITH; THACH]

The behavior of the climbing fiber system in the cerebellum is viewed in terms of resonances and rhythms. Building upon the anatomical modules in the target article by Simpson et al., the rhythmic behavior of the system is analyzed using a discrete approach. Rhythmic behavior requires oscillations of the olivary cells, but does not necessitate synchrony of complex spike activity. [HOUK et al.; SIMPSON et al.]

This commentary concerns the cerebellar contribution to cognition. It addresses the relevant historical background, elaborates upon the associative and paralimbic incorporation into both feedforward and feedback limbs of the cerebrocerebellar system, and relates this to the newly described cerebellar cognitive-affective syndrome. It then addresses the degree to which available anatomic data support current theories regarding nonmotor learning in the cerebellum, [HOUK et al.; THACH]

The target article by Thach outlines the Brindley-Marr-Albus-Gilbert (BMAG) learning theory and extends its validity to cognitive processes. We provide here an alternative explanation for the positron emission tomography (PET) data cited by Thach in support of the BMAG model. We also comment on the anatomical and physiological basis of the BMAG model and Houk's adjustable pattern generator (APG), both models being based on similar assumptions, [HOUK et al.; THACH]

In the behavioral literature on human movement, a distinction is made between the learning of parameters and the learning of new movement forms or topologies. Whereas the target articles by Thach, Smith, and Houk et al. provide evidence for cerebellar involvement in parametrization learning and adaptation, the evidence in favor of its involvement in the generation of new movement patterns is less straightforward. A case is made for focusing more attention on the latter issue in the future. This would directly help to bridge the gap between current neurophysiological approaches to the role of the cerebellum and the behavioral expressions of human motor learning, [HOUK et al.; SMITH; THACH]

For reasons I have never understood, some students of the cerebellum have been unwilling to accept the now overwhelming evidence that the cerebellum exhibits lasting synaptic plasticity and plays an essential role in some forms of learning and memory. With a few exceptions (e.g., target article by SIMPSON et al.) this is no longer the case, as is clear in the excellent target articles on cerebellar LTD and the excellent target review by HOUK et al. [CRÉPEL et al.; HOUR et al.; KANO; LINDEN; SIMPSON et al.; SMITH; VINCENT]

PET studies using classical conditioning paradigms are reported. It is emphasized that PET studies show “cerebellar involvement” and not “specific function” in learning paradigms. The importance of dissociating motor performance and learning deficits in human lesions studies is demonstrated in two exemplary studies. The different role of the cerebellum in adaptation of postural reflexes and learning of complex voluntary arm movements is discussed, [THACH]

Thach, following the Marr-Albus theory, suggests that the cerebellum contributes to sensorimotor learning through a process of context-response linkage. However, perceptual learning studies demonstrate that the context itself is subject to adaptive modifications and recent evidence has shown that motor responses derived from such perceptions display appropriate changes which may be quite independent of cerebellar processing. [HOUR et al.; SMITH; THACH]

It is argued that stiffness is, as Smith assumes, a likely movement-control parameter for the brain, as is supported by the results of several behavioral experiments. However, without further elaboration of what specific type and implementation of stiffness is meant it is perhaps premature to speculate on its possible locus of control, [SMITH]

Several target articles in this BBS special issue address the topic of cerebellar and olivary functions, especially as they pertain to motor earning. Another important topic is the neural interaction between the limbic system and the cerebellum during associative learning. In this commentary we present some of our data on olivo-cerebellar and limbic-cerebellar interactions during eyeblink conditioning. [HOUK et al.; SIMPSON et al.; THACH]

Studies comparing movement-related cortical potentials, post-excitatory inhibition after transcranial magnetic brain stimulation, and PET findings in normal controls and patients with cerebellar degeneration demonstrate plasticity of cerebro-cerebellar interactions and hereby support Thach's theory that the cerebellum has the ability to play a role in building behavioral context-response linkages and to build up appropriate responses from simpler constitutive elements, [THACH]

Two major themes have emerged in the commentaries elicited by the target articles that concern cerebellar long-term depression (LTD) (CRÉPEL, VINCENT, and LINDEN). First, is a lively debate concerning the potential role of a nitric oxide/cGMP cascade in cerebellar LTD induction. Second is a much broader issue relating to the interchange of information between cerebellar physiologists concerned with mechanisms at a cellular and synaptic level and those working at the level of systems physiology, behavior, or modeling. What contributions can cellular physiologists make to the study of motor learning? Cellular physiologists can provide testable hypotheses to help determine if these synaptic phenomena do underlie particular behaviors (e.g., if cerebellar LTD underlies vestibulo-ocular reflex [VOR] adaptation or eyeblink conditioning, then blockade of cerebellar LTD via, say, mGluRl inhibition, should interfere with these forms of motor learning). In addition, we can provide descriptive parametric information about basal synaptic function and use-dependent synaptic modifications that can constrain the range of models proposed to underlie a given behavior (e.g., are the timing constraints on LTD induction consistent with VOR adaptation or eyeblink conditioning?).

The target article on cellular mechanisms of long-term depression appears to have been well received by most authors of the relevant commentaries. This may be due to the fact that this review aimed to give a general account of the topic, rather than just describe previous work of the present author. The present response accordingly only raises questions of major interest for future research.

Several commentators argue that there remains a gap between cerebellar long-term depression (LTD) studied in vitro and cerebellar functions such as motor learning. Recent developments in a gene-targeting technique for producing mutant mice defective in particular gene products has opened a new era for the study of synaptic plasticity and learning. There are three mutants in which cerebellar LTD are clearly deficient in vitro. Two of these mice show clear impairment in the conditioned eyeblink response, a paradigm known to involve the cerebellum. In contrast, one mutant with apparently normal cerebellar LTD showed no impairment in the conditioned eyeblink response. These new lines of evidence support the view that cerebellar LTD is a cellular basis for discrete motor learning.

Although a number of further studies have now been published exploring possible roles for the NO-cGMP signal transduction system in various models of LTD, there still appears to be confusion regarding the physiological functions of these molecules in the cerebellar cortex. What seems clear is that NO can be produced in granule cells and basket cells, and can stimulate soluble guanylyl cyclase, thereby activating cGMP-dependent protein ldnase in Purkinje cells. However, substrates for this Idnase are still poorly defined, and its role in the modulation of synaptic transmission remains to be determined. The recent development of novel transgenic models and new pharmacological agents with which to dissect this signal transduction system, gives one confidence that our understanding of the cerebellar NO system will quickly advance. With its unique properties as a signaling molecule, it is clear that NO news has been good news for those studying synaptic plasticity in the cerebellum.

Neural models are needed at many levels, ranging from the biophysically based to connectionist abstractions. The adjustable pattern generator (APG) model of the cerebellum discussed in the target article by Houk, Buckingham, and Barto operates at an intermediate level and is constrained by a large body of anatomical and physiological data. The associative memory model originally proposed by Marr (1969) and Albus (1971) on the basis of the microcircuitry of the cerebellar cortex is still relevant today, although it needs to be coupled to the problem of motor pattern generation. In considering the problem of cerebellar learning, one needs some source of training information to adjust network performance so that it performs fruitful interactions with the environment; however, it is not true that this “teacher” needs to be particularly smart. We address these and other important issues raised by the commentators.

Several themes can be identified in the commentaries. The first is that the climbing fibers may have more than one function; the second is that the climbing fibers provide sensory rather than motor signals. We accept the possibility that climbing fibers may have more than one function – hence ‘consequence(s)’ in the title. Until we know more about the function of the inhibitory input to the inferior olive from the cerebellar nuclei, which are motor structures, we have to keep open the possibility that the climbing fiber signals can be a combination of sensory and motor signals.

In response to several requests from commentators, an unambiguous definition of time-varying joint stiffness is provided. However, since a variety of different operations can be used to measure stiffness, a problem for quantification admittedly still exists. Several commentaries pointed out the advantage of controlling joint stiffness in optimizing the speed-accuracy trade-off known as Fittss law. The deficit in rapid reciprocal movements and the impact on joint stiffness inhibition caused by cerebellar lesions is clarified here, as the target article was apparently misinterpreted by some readers. In response to the challenge that there is little consensus among cerebellar physiologists, several areas of tacit agreement with other theories of cerebellar function are enumerated. An alternative interpretation of studies showing a transient activation of the cerebellum in motor learning is suggested. Finally, the relationship between the command signals generated by supraspinal centers such as the cerebellum and spinal interneuron networks controlling muscle synergies is discussed.

The target article reviews studies of human cerebellar functional imaging and ablation in motor learning. This material is integrated with anatomical and physiological work in laboratory animals. A synthesis is presented as a working hypothesis on how the cerebellum might adapt, learn, and coordinate movement. An attempt is made to extend the motor role to certain mental operations, particularly those associated with mental movement. These notions met with varying enthusiasm. A few commentators seemed pleased with the overall result and offered supportive ideas. Some were critical of the proposed contributions to cognition and motor learning. A surprising number insisted that the cerebellum was more concerned with sensory processing than with movement management. Some thought we know too little to attempt such a synthesis.