Online research in philosophy

Long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy that many consider the best candidate currently available for a neural mechanism of memory formation and (...) class='Hi'>/or storage in the mammalian brain. In our target article, LTP: What's learning got to do with it?, we concluded that there was insufficient data to warrant such a conclusion. In their commentaries, Jeffery and Zhadin raise a number of important issues that we did not raise, both for and against the hypothesis. Although we agree with a number of these issues, we maintain that there remains insufficient evidence that LTP is a memory mechanism. (shrink)

The structuralist program has developed a useful metascientific resource: ontological reductive links (ORLs) between the constituents of the potential models of reduced and reducing theories. This resource (...) was developed initially to overcome an objection to structuralist ``global'' accounts of the intertheoretic reduction relation. But it also illuminates the way that concepts at a higher level of scientific investigation (e.g., cognitive psychology) become ``structured through reduction'' to lower-level investigations (e.g., cellular/molecular neuroscience). After (briefly) explaining this structuralist background, I demonstrate how this resource illuminates an actual, emerging scientific example: the link between the psychological concept of a ``consolidation switch'' from short-term to long-term memory and the cellular/molecular mechanisms of the transition from early- to late-phases of long-term potentiation (LTP) (an important type of synaptic plasticity in mammalian hippocampus and cortex). (shrink)

Shors & Matzel provide compelling arguments against a role for hippocampal long-term potentiation (LTP) in mammalian learning and memory. As an alternative, they suggest that LTP is (...) an arousal mechanism. I will argue that this view is not a satisfactory alternative to current conceptions of LTP function. (shrink)

The neurophysiological phenomenon of LTP (long term potentiation) is considered by many to represent an adequate mechanism for acquiring or storing memories in the mammalian brain. In (...) our target article, we reviewed the various arguments put forth in support of the LTP/memory hypothesis. We concluded that these arguments were inconsistent with the purported data base and proposed an alternative interpretation that we suggested was at least as compatible with the available data as the more widely held view. In doing so, we attempted to illustrate that the inadequacy of present experimental designs did not permit us to distinguish between equally viable hypotheses. In the four years since we wrote the first draft of our target article, hundreds of additional studies on LTP have been published and their results have been incorporated into current theories about memory. A diverse group of commentators responded to our target article with their own theories of how memories might be stored in the brain, some of which rely on LTP. Some commentators doubted whether memories can be stored through modifications of synaptic strength. Some assert that it will never be possible to understand the neural mechanisms of memory; still others remain hopeful that we will accomplish some semblance of a resolution, provided we appreciate LTP's role in a subset of seemingly amorphous memory systems. In summary, although it is commonly written that “LTP is a memory storage device,” the divergence of views among the commentators suggests, at least as strongly as our target article, that such conviction is unwarranted and fails to acknowledge both the lack of consensus regarding the role of LTP in memory and the complexity of the phenomenon of memory itself. (shrink)

The problem of neural memory storage is discussed,<span class='Hi'>span> based on the results of studies of memory impairment after hippocampal lesions,<span class='Hi'>span> motor (...) learning,<span class='Hi'>span> and electrophysiological research on <span class='Hi'>span>“spinal memory.<span class='Hi'>span>” I support Shors <span class='Hi'>span>& Matzel's major statements.<span class='Hi'>span> The absence of reliable evidence on the LTP memory storage function and other data cast doubt on the synaptic theory of memory. (shrink)

Shors & Matzel (1997) suggest replacing the question “Is LTP a mechanism of learning?” with “Is LTP a mechanism of arousal and attention?” However, the failure of experiments (...) class='Hi'> to verify the LTP-learning hypothesis may arise not because it is untrue, but because in its current guise, it is not properly testable. If so, then the LTP-attention hypothesis is untestable, as well. (shrink)

Shors & Matzel's conclusion that LTP is not related to learning is similar to one we reached several years ago. We discuss some methodological advances that have (...) relevance to the issue and applaud the authors for challenging existing dogma. (shrink)

Since learning emerges from a circuit mediating behavior it is unrealistic to require LTP to be a sufficient explanation of it; however, LTP is a necessary component (...) of some learning circuits. The properties of that component bear a closer formal relationship to the acquisition of associative strength than to the modulation of attention. (shrink)

LTP is thought to be an experimental model for studying the cellular mechanism of learning and memory. Shors & Matzel review some contradictory data concerning the linkage between (...) class='Hi'> LTP and memory and suggest that LTP does not underlie learning and memory. LTP is a cellular and synaptic process and cannot be a memory mechanism. In fact, it is a cellular information storage mechanism. (shrink)

The hypothesis that there is a 1:1 correspondence between LTP and learning is simplistic, and the correlation approach to testing it is therefore too limited. The (...) class='Hi'>alternative hypothesis that LTP plays a role in arousal is consistent with activity-dependent neuromodulation, but ignores the Hebbian properties of LTP. LTP may involve both types of mechanisms, suggesting a possible synthesis of the two hypotheses. (shrink)

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.

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. (shrink)

Despite close scrutiny in recent years, the traditional properties of LTP are holding up remarkably well, and they remain a credible influence on the belief that LTP (...) has something to do with learning and information storage. (shrink)

Shors and Matzel's evaluation of approaches to the behavioural function of LTP is welcome, and should encourage a widening of conceptual approaches to this problem. In (...) class='Hi'>addition to their call for increased sophistication in thinking about LTP, there needs to be a parallel increase in sophistication in the study of behaviour. Changes in emotional state or tone may be a better function for LTP than attention mechanisms. (shrink)

Gene targeting has generated a great deal of data on the molecular mechanisms of long-term potentiation and its potential role in learning and memory. However, the (...) class='Hi'>interpretation of some results has been questioned. Compensatory mechanisms and the contribution of genetic background may make it difficult to unequivocally prove the existence of a causal (genetic) link between LTP and learning. (shrink)

The absence of a clear influence of the responses modified by new connections created by LTP on the development of these connections casts doubt on an essential (...) role of LTP in learning and memory formation without any association with reinforcement. The evidence for the involvement of the monoaminergic systems in synaptic potentiation in the cerebral cortex during learning is adduced, and their role in reinforcement system function is discussed. (shrink)

This commentary argues that (1) arousal is not sufficient to induce LTP in the hippocampus, (2) learning can profoundly modulate synaptic plasticity in a state-dependent manner (...) class='Hi'>without affecting baseline synaptic efficacy, and (3) unilateral, synapse-specific LTP induction triggers an interhippocampal communication manifested as bilateral increases in gene expression at multiple sites in the hippocampal network. (shrink)

Recent evidence from our lab indicates that LTP shares an important property with memory consolidation: it is consolidated by natural reinforcement. Nevertheless, the hypothesis, that LTP-like (...) class='Hi'>mechanisms or other forms of enhanced synaptic efficacy are basic elements in learning is not unequivocally supported. Skepticism aside, LTP is an accessible experimental model that is optimally equipped for the investigation of the cellular and molecular machinery involved in synaptic weight changes. (shrink)

Shors & Matzel somewhat lightly dismiss the evidence that a process like LTP may underlie the learning-induced increase in neuronal activity in the hippocampus in eyeblink conditioning. (...) I provide some 12 lines of evidence supporting this hypothesis and the further hypothesis that this learning-induced LTP-like hippocampal plasticity can play a critical role in certain aspects of learned behavior. (shrink)

We argue in this paper that so-called new wave reductionism fails to capture the nature of the interlevel relations between psychology and neuroscience. Bickle (1995, Psychoneural (...) class='Hi'>reduction of the genuinely cognitive: some accomplished facts, Philosophical Psychology, 8, 265-285; 1998, Psychoneural reduction: the new wave, Cambridge, MA: MIT Press) has claimed that a (bottom-up) reduction of the psychological concepts of learning and memory to the concepts of neuroscience has in fact already been accomplished. An investigation of current research on the phenomenon of long-term potentiation reveals that this claim overstates the facts. Both the psychological and the neural concepts involved have not yet stabilized and face further correction under the influence of both bottom-up and top-down selection pressures. In addition, psychological concepts often refer to functions, and functions are indispensable and irreducible. Function ascriptions pick out objective patterns involving historical factors and distal goals. This view of functions implies that psychological facts cannot be simply read off from the neurophysiological facts. Although psychological theorizing is constrained by neurophysiology (and vice versa), psychology remains distinct at least to some degree. (shrink)

A fundamental assumption in Shors & Matzel's target article is that brain activity can be related to the traditional categories of mentalistic psychology. This has led them (...) to make numerous further assumptions that are contradicted by the available evidence. (shrink)

As opposed to the dismissive attitude toward reductionism that is popular in current philosophy of mind, a “ruthless reductionism” is alive and thriving in “molecular and cellular (...) cognition”—a field of research within cellular and molecular neuroscience, the current mainstream of the discipline. Basic experimental practices and emerging results from this field imply that two common assertions by philosophers and cognitive scientists are false: (1) that we do not know much about how the brain works, and (2) that lower-level neuroscience cannot explain cognition and complex behavior directly. These experimental practices involve intervening directly with molecular components of sub-cellular and gene expression pathways in neurons and then measuring specific behaviors. These behaviors are tracked using tests that are widely accepted by experimental psychologists to study the psychological phenomenon at issue (e.g., memory, attention, and perception). Here I illustrate these practices and their importance for explanation and reduction in current mainstream neuroscience by describing recent work on social recognition memory in mammals. (shrink)

Long-Term Potentiation (LTP) is a kind of synaptic plasticity that many contemporary neuroscientists believe is a component in mechanisms of memory. This essay describes the discovery (...) class='Hi'>of LTP and the development of the LTP research program. The story begins in the 1950's with the discovery of synaptic plasticity in the hippocampus (a medial temporal lobe structure now associated with memory), and it ends in 1973 with the publication of three papers sketching the future course of the LTP research program. The making of LTP was a protracted affair. Hippocampal synaptic plasticity was initially encountered as an experimental tool, then reported as a curiosity, and finally included in the ontic store of the neurosciences. Early researchers were not investigating the hippocampus in search of a memory mechanism; rather, they saw the hippocampus as a useful experimental model or as a structure implicated in the etiology of epilepsy. The link between hippocampal synaptic plasticity and learning or memory was a separate conceptual achievement. That link was formulated in at least three different ways at different times: reductively (claiming that plasticity is identical to learning), analogically (claiming that plasticity is an example or model of learning), and mechanistically (claiming that plasticity is a component in learning or memory mechanisms). The hypothesized link with learning or memory, coupled with developments in experimental techniques and preparations, shaped how researchers understood LTP itself. By 1973, the mechanistic formulation of the link between LTP and memory provided an abstract framework around which findings from multiple perspectives could be integrated into a multifield research program. (shrink)

Insights into the role of sleep in the molecular mechanisms of memory consolidation may come from studies of activity-dependent synaptic plasticity, such as long-term potentiation (LTP (...) class='Hi'>). This commentary posits a specific contribution of sleep to LTP stabilization, in which mRNA transported to dendrites during wakefulness is translated during sleep. Brain-derived neurotrophic factor may drive the translation of newly transported and resident mRNA. (shrink)

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 (...) class='Hi'>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. (shrink)

Pains that persist long after damaged tissue hasrecovered remain a perplexing phenomenon. Theseso-called chronic pains serve no useful function foran organism and, given its disabling effects, (...) class='Hi'>mighteven be considered maladaptive. However, a remarkablesimilarity exists between the neural bases thatunderlie the hallmark symptoms of chronic pain andthose that subserve learning and memory. Bothphenomena, wind-up in the pain literature andlong-term potentiation (LTP) in the learning andmemory literature, are forms of neuroplasticity inwhich increased neural activity leads to a longlasting increase in the excitability of neuronsthrough structural modifications at pre- andpost-synaptic sites. Moreover, the synapticmodifications of wind-up and LTP share a commonmechanism: a glutamate N -methyl-D-aspartate(NMDA) receptor interaction that initiates a calciummediated biochemical cascade that ultimately enhancessignal processing at the -amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor. This paper arguesthat chronic pain, which has no adaptive value, canbe accounted for in terms of the highly adaptivephenomenon of activity-dependent neural plasticity;hence, some cases of chronic pain can beconceptualized as a memory trace in spinal neurons. (shrink)

Shors & Matzel set up a straw man, that LTP is a memory storage mechanism, and knock him down without due consideration of the important relations among different (...) class='Hi'> levels of organization and analysis regarding LTP, learning, and memory. Assessing these relationships requires analysis and hypotheses linking specific brain regions, neural circuits, plasticity mechanisms, and task demands. The issue addressed by the authors is important, but their analysis is off target. (shrink)

We agree with Shors & Matzel's general hypothesis that the proposed link between NMDA-dependent LTP and memory is weak. They suggest that NMDA-dependent LTP is important (...) class='Hi'> to arousal or attentional processes which influence learning in an anterograde manner. However, current evidence is also consistent with the view that NMDA receptors modulate memory consolidation retroactively, as occurs in several other receptor classes. (shrink)

Several types of amygdala-dependent learning can be blocked by local infusion of NMDA antagonists into the amygdala. This blockade shows anatomical, pharmacological, temporal, and behavioral specificity, (...) class='Hi'>providing a pattern of data more consistent with a role for NMDA receptors in learning than in arousal or attention, and supporting the contention that an “LTP-like” process is a neural substrate for memory formation. (shrink)

Examples of how LTP and LTD can control adaptively-timed learning that modulates attention and motor control are given. It is also suggested that LTP/LTD can play (...) class='Hi'> a role in storing memories. The distinction between match-based and mismatch-based learning may help to clarify the difference. (shrink)

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. (shrink)

Controversy surrounds several experiments that have addressed whether selective synaptic strengthening occurs during learning. To date, the evidence suggests that widespread alterations in synaptic strength, through either (...) kindling or electroconvulsive shock, can disrupt this hypothetical process. The lack of evidence for selective modification of learning through LTP stimulation, however, provides difficulties for both the prevailing hypothesis and the hypothesis advanced by Shors & Matzel. Subsequent experiments may indicate a role for LTP in both learning and arousal. (shrink)

Shors & Matzel propose that hippocampal LTP increases the effective salience of discrete external stimuli and thereby facilitates the induction of memories at distant places. In line with (...) class='Hi'> this suggestion, a neural network model of associative learning and hippocampal function assumes that LTP increases hippocampal error signals to the cortex, thereby facilitating stimulus configuration in association cortex. Computer simulations show that under these assumptions the model correctly describes the effect of LTP induction and blockade in classical discriminations and place learning. (shrink)

What distinguishes good explanations in neuroscience from bad? Carl F. Craver constructs and defends standards for evaluating neuroscientific explanations that are grounded in a systematic view of (...) what neuroscientific explanations are: descriptions of multilevel mechanisms. In developing this approach, he draws on a wide range of examples in the history of neuroscience (e.g. Hodgkin and Huxley's model of the action potential and LTP as a putative explanation for different kinds of memory), as well as recent philosophical work on the nature of scientific explanation. Readers in neuroscience, psychology, the philosophy of mind, and the philosophy of science will find much to provoke and stimulate them in this book. (shrink)