There is no general agreement as to the meaning of long-term potentiation, but this cannot be resolved by using it to explain additional phenomena. Increased attention to recently experienced stimuli is a form of learning known to neuropsychologists as repetition priming. As more is learned about the neurochemistry of synaptic change, the term LTP will wither.

Although clinical studies and animal models seem to establish an important role for the sympathetic nervous system in many forms of neuropathic and inflammatory pain, there is an ongoing debate on the classification of pain syndromes with sympathetic components. The confusion originates from several sources: failure to acknowledge that the pathomechanism of chronic pain can change during the progress of the disease, which is now strongly underlined by experimental data from suitable animal models. Neuropathic pain is a vaguely defined collection of pain syndromes which includes painful conditions with diverse and largely unknown patho-mechanisms. Clinical diagnosis is difficult and well designed, placebo controlled sympathectomy is rarely performed. [blumberg et al.]

Exploiting existing representations implies tapping an enormous domain, coextensive with human understanding and knowledge, and endowed with its own dynamics of piecewise and cumulative learning. The worth of Clark & Thornton's proposal depends on the relative importance of this dynamics and of the bottom-up mechanism they come to complement. Radical restructuring of theories and patterns of retrieval from long-term memory are discussed in the context of such an evaluation.

Prefrontal cerebral areas project to Purkinje cells, located in the most lateral part of the cerebellum, via mossy and climbing fibers. The latter olivary error signals reflect the attentional load of the prefrontal cortex. At the cerebral level, LTP-LTD plasticity allows these Purkinje cells to adaptively reinforce the active pyramidal cells involved in the motor sequence.

In the developing and adult cortex, just as in the adult hippocampus, LTP is unable to account for a variety of types of functional plasticity.

The brain seems to be able to generate and uphold sensitization by itself, based on previous experience, or genetic disposition. This seems to be particularly important for muscle pain. There seem to be positive feedback loops where pain produces more pain, and more sensitization. Musculoskeletal pain is the most common pain state. It amounts to almost 50% of all long term sickness absence. But other subjective complaints are also common, and may depend on sensitization. Sensitization has been introduced as an explanation for subjective complaints from the gastrointestinal tract and the brain, like fatigue, tiredness, dizziness, and vertigo. [coderre & katz]

Connectionist networks excel at extracting statistical regularities but have trouble extracting higher-order relationships. Clark & Thornton suggest that a solution to this problem might come from Elman (1993), but I argue that the success of Elman's single recurrent network is illusory, and show that it cannot in fact represent abstract relationships that can be generalized to novel instances, undermining Clark & Thornton's key arguments.

The cerebellum has been hypothesized to play a role in a variety of movement timing tasks that involve the processing of temporal information on a variety of timescales. Braitenberg, Heck & Sultan propose a new theory of cerebellar function that is able to account for movement timing on the order of a couple of hundred milliseconds. However, this theory does not account for the rôle the cerebellum plays in the acquisition and retention of adaptively timed discrete movements that are on the order of 200 to 1000 milliseconds, and therefore does not account for the entire temporal range of cerebellar dependent processing.

Recoding the data for relational learning is both easier and more difficult than it might appear. Human beings routinely find the appropriate representation for a given problem because coding always takes place within the framework of a domain, theory, or background knowledge. How this can be achieved is still highly speculative, but should probably be investigated with hybrid models.

This commentary on coderre & katz, wiesenfeld-hallin et al., and dickenson focuses on: (a) the brain as an under-recognized contributor to pain facilitation at the spinal cord; (b) these brain-to-spinal pathways being activated by learning or by body infection/inflammation; and (c) the resultant spinal release of anti-analgesic neuropeptides, activators of the NMDA-NO cascade, and activators of glia.

Precise timing of muscle contractions is an important prerequisite for motor control and one to which the cerebellum contributes. Braitenberg et al.'s detailed timing hypotheses relate only to a subset of the known features of the organisation of the cerebellum. However, the cerebellar architecture clearly supports the “tidal waves” that are central to the authors' proposal and such tidal waves are very likely to contribute to its functions.

Although it is not their fault, Shors & Matzel's attempt to review the LTP and learning hypothesis suffers from there being no clear published statement of the idea. Their summary of relevant evidence is not without error, however, and it oversimplifies fundamental issues relating to NMDA receptor function. Their attentional hypothesis is intriguing but requires a better systems-level understanding of how attention contributes to cognitive function.

Intradermal capsaicin in humans causes pain, primary hyperalgesia, and secondary mechanical hyperalgesia and allodynia. Parallel changes occur in the responses of primate spinothalamic tract cells and in rat behavior. Neurotransmitters that trigger secondary mechanical hyperalgesia and allodynia include excitatory amino acids and substance P. Secondary mechanical allodynia is actively maintained by central mechanisms. Our group has investigated mechanisms of central sensitization of nociceptive neurons by examining the responses to intradermal injection of capsaicin. These experiments are pertinent to issues raised by coderre & katz (sect. 2).

Shors & Matzel's target article is a thought-provoking attempt to reconceptualise long-term potentiation as an attentional or arousal mechanism rather than a memory storage mechanism. This is incompatible with the facts of the neurobiology of attention and of the behavioural neurophysiological properties of hippocampal neurons.

Clark & Thornton speculate that intervening in the real world might be a way of transforming type-2 problems into type-1, but they state that they are not aware of any definite cases. It is argued that the active construction of external representations often performs exactly this function, and that recoding via the real world is therefore common, if not ubiquitous.

The central hypothesis of Braitenberg et al.'s target article – that tidal waves of parallel fiber excitation precisely activate Purkinje cell spiking – is hard to reconcile with recent neurophysiological and modeling data. The assumed pattern of mossy fiber input seems unrealistic, inhibition is likely to interfere with the proposed excitatory responses, and moreover, computer simulations show that the Purkinje cell is a poor coincidence detector.

Despite significant advances in pain research and clinical pain management, little effort has been devoted to exploring whether the same pain treatment strategies are effective for male and female patients. Recent studies indicate that sex differences might play a role in the response to noxious events and in the response to analgesic interventions (berkley). Further insight into these gender differences will lead to improved pain management for women and men.

Preoccupation with LTP as a putative memory mechanism may have retarded the consideration of pathological modulation of synaptic plasticity in clinical disorders where memory dysfunction is not a primary feature. Encouraged by Shors & Matzel's review, we consider the relationship between stress, synaptic plasticity, and depressive disorder.

Learning is the acquisition of knowledge, not of input/output mappings. The distinction between statistical and relational learning, as Clark & Thornton define those terms, is not useful because all human learning is relational. However, prior knowledge does influence later learning and the sequence in which learning tasks are encountered is indeed crucial. Simulations of sequence effects would be interesting.

A propagator for a path space integral can be used to represent the “tidal wave function” and provides a natural way to model a control signal that is temporally segmented by placement of pairs of stimulating and recording electrodes. Although care must be exercised in interpreting the resulting measurement, the technique should prove useful to experimenters who study cerebellar functioning.