Showing papers on "Developmental plasticity published in 2002"

Somatic cell nuclear transfer.

Abstract: Cloning by nuclear transfer from adult somatic cells is a remarkable demonstration of developmental plasticity. When a nucleus is placed in oocyte cytoplasm, the changes in chromatin structure that govern differentiation can be reversed, and the nucleus can be made to control development to term.

The developmental origins of adult disease.

Abstract: Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of developmental plasticity, the phenomenon by which one genotype can give rise to a range of different physiological or morphological states in response to different environmental conditions during development. Recent observations have shown that impaired growth in infancy and rapid childhood weight gain exacerbate the effects of impaired prenatal growth. A new vision of optimal early human development is emerging which takes account of both short and long-term outcomes.

Hormones, developmental plasticity and adaptation

Abstract: Phenotypic plasticity is the extent to which an organism can change its physiology, behaviour, morphology and/or development in response to environmental cues. Environmentally induced differences in the endocrine system are among the underlying causes of phenotypic plasticity. For example, maternal and other environmental influences on developing young can affect the range of physiological and behavioural responses available to them as adults. The mechanisms underlying phenotypic plasticity can be elucidated using multidisciplinary approaches, in which the dynamic interactions among developmental, hormonal and environmental factors are considered. Such studies point to the importance of considering the overall developmental trajectory of an organism when assessing the adaptive value of phenotypic variation, rather than simply evaluating the individual at a single point in time.

Neural Plasticity: The Effects of Environment on the Development of the Cerebral Cortex

Abstract: Acknowledgments Introduction 1 Neuroanatomical Substrates: Early Developmental Events 2 Synaptogenesis 3 Methods for the Study of Functional Plasticity 4 Plasticity in Sensory Systems 5 Plasticity in the Motor Cortex 6 Plasticity in the Development of Language 7 Plasticity in Elective Brain Functions 8 Adult Plasticity 9 Summing Up 10 The Practical Relevance of the Findings from Developmental Neurobiology References Index

Thermal plasticity of skeletal muscle phenotype in ectothermic vertebrates and its significance for locomotory behaviour.

Abstract: Seasonal cooling can modify the thermal preferenda of ectothermic vertebrates and elicit a variety of physiological responses ranging from winter dormancy to an acclimation response that partially compensates for the effects of low temperature on activity. Partial compensation of activity levels is particularly common in aquatic species for which seasonal temperature changes provide a stable cue for initiating the response. Thermal plasticity of locomotory performance has evolved independently on numerous occasions, and there is considerable phylogenetic diversity with respect to the mechanisms at the physiological and molecular levels. In teleosts, neuromuscular variables that can be modified include the duration of motor nerve stimulation, muscle activation and relaxation times, maximum force and unloaded shortening velocity (V(max)), although not all are modified in every species. Thermal plasticity in V(max) has been associated with changes in myosin ATPase activity and myosin heavy chain (MyHC) composition and/or with a change in the ratio of myosin light chain isoforms. In common carp (Cyprinus carpio), there are continuous changes in phenotype with acclimation temperature at lower levels of organisation, such as MyHC composition and V(max), but a distinct threshold for an effect in terms of locomotory performance. Thus, there is no simple relationship between whole-animal performance and muscle phenotype. The nature and magnitude of temperature acclimation responses also vary during ontogeny. For example, common carp acquire the ability to modify MyHC composition with changes in acclimation temperature during the juvenile stage. In contrast, the thermal plasticity of swimming performance observed in tadpoles of the frog Limnodynastes peronii is lost in the terrestrial adult stage. Although it is often assumed that the adjustments in locomotory performance associated with temperature acclimation enhance fitness, this has rarely been tested experimentally. Truly integrative studies of temperature acclimation are scarce, and few studies have considered both sensory and motor function in evaluating behavioural responses. Developmental plasticity is a special case of a temperature acclimation response that can lead to temporary or permanent changes in morphology and/or physiological characteristics that affect locomotory performance.

Addiction: making the connection between behavioral changes and neuronal plasticity in specific pathways.

Abstract: 146 T here is an emerging consensus that drug addiction is a form of maladaptive learning. Drugs of abuse usurp the neuronal circuitry involved in motivation and reward, leading to aberrant engagement of learning processes. As a result, drug-associated cues can trigger craving and compulsive drug-seeking behavior, and voluntary control over drug use is lost. Abused drugs can also modulate long-term potentiation (LTP) and long-term depression (LTD) in neuronal circuits associated with the addiction process, suggesting a way for the behavioral consequences of drug-taking to become reinforced by learning mechanisms. This review will assess progress in correlating these effects on LTP and LTD with behavioral changes in animal models of addiction, particularly behavioral sensitization. The image evokes the alluring yet sinister nature of cocaine. By usurping neuronal pathways normally involved in motivated behavior, cocaine promotes \"learning\" of compulsive behavioral responses that underlie drug craving and addiction.

Human brain plasticity: evidence from sensory deprivation and altered language experience.

Abstract: The results from the language studies taken as a whole point to different developmental time courses and developmental vulnerabilities of aspects of grammatical and semantic/lexical processing. They thus provide support for conceptions of language that distinguish these subprocesses within language. Similarly, following auditory deprivation, processes associated with the dorsal visual pathway were more altered than were functions associated with the ventral pathway, providing support for conceptions of visual system organization that distinguish functions along these lines. Could the effects observed in blind and deaf adults be accounted for, at least in part, by the redundant connectivity of the immature human brain? One way we tested this hypothesis was to study the differentiation of visual and auditory sensory responses in normal development (Neville, 1995). In normal adults, auditory stimuli elicit ERP responses that are large over temporal brain regions but small or absent over occipital regions. By contrast, in 6-month-old children we observed that auditory ERPs are equally large over temporal and visual brain regions, consistent with the idea that there is less specificity and more redundancy of connections between the auditory and visual cortex at this time. Between 6 and 36 months, however, we observed a gradual decrease in the amplitude of the auditory ERP over visual areas, while the amplitude over the temporal areas was unchanged. These results suggest that early in human development, there exists a redundancy of connections between auditory and visual areas and that this overlap gradually decreases after birth. This loss of redundancy may be a boundary condition that determines when sensory deprivation can result in alterations in the organization of remaining sensory systems. The considerable variability in timing of sensitive periods may also be in part due to temporal differences in the occurrence of redundancy within different systems. Ongoing studies of infants and children employing different types of stimuli will test for the specificity of these effects (Mitchell et al., 1999). Differences in the degree of plasticity may also be due to differences in the overall level of redundant connectivity within different systems. For example, it may be that aspects of sensory systems that are specialized for high spatial acuity (e.g., central vision and central audition) exhibit fewer developmental redundancies, decreased modifiability and more specificity than those displaying less acuity and precision (e.g., peripheral representations within vision and audition). There is some evidence for this hypothesis within the visual system (Chalupa and Dreher, 1991). In addition, there may be molecular differences between systems displaying different levels and patterns of experience-dependent plasticity. It is of interest that all levels of the dorsal pathway of the visual system, which in the studies reviewed here shows a high level of modifiability, displays strong immunoreactivity for the monoclonal antibody CAT 301 in macaque monkeys (DeYoe et al., 1990). By contrast there is very little labeling within the ventral visual pathway. Moreover, the expression of CAT 301 immunoreactivity shows marked experience-dependent plasticity, suggesting it may play a role in the guidance and/or stabilization of synaptic structure (Sur et al., 1988). Further research along these lines within the auditory system and in animal models of sensory deprivation and other developmental disorders may elucidate the role of specific molecular factors in the developmental plasticity of different neural systems. A related, more general hypothesis that may account for the different patterns of plasticity within both vision and language is that systems employing fundamentally different learning mechanisms (perhaps mediated by different anatomical and molecular substrates) display different patterns of developmental plasticity. It may be that systems that display experience-dependent change throughout life, including the topography of sensory maps (Merzenich et al., 1988; Gilbert, 1995; Kaas, 1995), lexical acquisition (i.e. object-word associations), and the establishment of form, face, and object representations (i.e., ventral pathway functions) rely upon very general, associative learning mechanisms that permit learning and adaptation throughout life. By contrast, systems that are important for computing dynamically shifting relations among locations, objects and events (including the dorsal visual pathway and the systems of the brain that mediate grammar) appear dependent on and modifiable by experience primarily during more limited periods in development. This could account for both the greater developmental deficits and enhancements of dorsal pathway function following various developmental anomalies and for the greater effects of altered language experience on grammatical functions. Further research is necessary to characterize systems that become constrained in this way and those that can be modified throughout life. This type of developmental evidence can contribute to fundamental descriptions of the architecture of different cognitive systems and can guide future studies of the cellular and molecular mechanisms important in neuroplasticity. Additionally, in the long run, they may contribute to the design of educational and habilitative programs for both normally and abnormally developing children.

Ecological constraints on the evolution of plasticity in plants

Abstract: Signal detection and response are fundamental to all aspects of phenotypic plasticity. This paper proposes a novel mechanism that may act as a general limit to the evolution of plasticity, based on how selection on signal detection and response is likely to interact with gene flow in a spatially autocorrelated environment. The factors promoting the evolution of plasticity are re- viewed, highlighting the crucial role of information acquisition and developmental lags, and of selection in spatially and temporally structured habitats. Classic studies of the evolution of plasticity include those on shade avoidance, on morphological plasticity in clonal plants, and on selection in spatially structured model populations. Comparative studies indicate that, among clonal plants, extensive plasticity in growth form is favored in patchy environments, as expected. However, among woody lineages from Madagascar, plasticity in photosynthetic pathway (CAM vs. C3) appears to confer competitive success in areas of intermediate drought stress, rather than allowing individually plastic species to expand their ranges, as has often been argued. The extent of phenotypic plasticity cannot only determine species distributions, it can also affect the sign and magnitude of interactions between species. There appears to be some relationship between developmental plasticity and evolutionary lability: traits that show relatively few transitions within and among plant lineages (e.g., zygomorphy vs. actinomorphy, phyllotaxis, fleshy vs. capsular fruits) usually show no plas- ticity within individual plants; traits that show extensive plasticity within individuals or species (e.g., leaf size, flower number, plant height) generally also show extensive variation within and across lineages. Transaction and cybernetic costs, as well as long-lived leaves or roots, can limit the tempo of adaptive developmental responses, and create a hierarchy of responses at different temporal scales. Traits whose variation entails few transaction costs (e.g., stomatal conductance) are more likely to be shifted more frequently than those with higher costs of variation (e.g., leaf cross-sectional anatomy). The envelope of responses at the physiological and developmental time scales appears to be an important determinant of adaptive performance. However, adaptive plasticity can limit its own range of effectiveness as a consequence of energetic and competitive constraints, as seen in the allometry and zonation of emergent vs. floating aquatic plants. Plants' inherently low rate of energy capture (and, hence, developmental response and growth) and the high energetic costs of a central nervous system (CNS), may explain why they lack a brain and integrate environmental signals with a slow, hormone-based set of feedback loops rather than with a fast CNS. Finally, environmental spatial autocorrelations - especially those involving factors that determine optimal phenotype - can combine with gene flow and selection for reliance on the locally most informative signals to produce a fundamental limit on the extent of adaptive plasticity.

Do apoptotic mechanisms regulate synaptic plasticity and growth-cone motility?

Abstract: Signals between neurons are transduced primarily by receptors, and second messenger and kinase cascades, located in pre- and postsynaptic terminals. Such synaptic signaling pathways include those activated by neurotransmitters, cytokines, neurotrophic factors, and cell-adhesion molecules. Many of these signaling systems are also localized in the growth cones of axons and dendrites, where they control pathfinding and synaptogenesis during development. Although it has been known for decades that such signaling pathways can affect the survival of neurons, by promoting or preventing a form of programmed cell death known as apoptosis, we have discovered that apoptotic biochemical cascades can exert local actions on the functions and structural dynamics of growth cones and synapses. In this article, we provide a brief background on apoptotic biochemical cascades, and present examples of studies in this laboratory that have identified novel apoptotic and anti-apoptotic signaling mechanisms that are activated and act locally in synapses, growth cones, and dendrites to modify their structure and function. Apoptotic synaptic cascades that may play roles in neuronal plasticity include activation of caspases that can cleave certain types of ionotropic glutamate-receptor subunits and thereby modify synaptic plasticity. Caspases may also cleave cytoskeletal protein substrates in growth cones of developing neurons and may thereby regulate neurite outgrowth. Par-4 and the tumor-suppressor protein p53 are pro-apoptotic proteins that may also function in synaptic and developmental plasticity. Examples of anti-apoptotic signals that regulate the plasticity of growth cones and synapses include neurotrophic factor-activated kinase cascades, calcium-mediated actin depolymerization, and activation of the transcription factor NF-κB. The emerging data strongly suggest that many of the signaling mechanisms that control apoptosis are also involved in regulating the structural and functional plasticity of neuronal circuits under physiological conditions.

Effects of enriched environment and fluid percussion injury on dendritic arborization within the cerebral cortex of the developing rat

Abstract: We have recently demonstrated that fluid percussion injury (FPI) sustained early in life prevents the neural plasticity response associated with rearing in an enriched environment (EE). In order to determine if this reduction in plasticity capacity is reflected in alterations in dendritic arborization, the present study examined dendritic changes in response to EE, FPI, and FPI followed by EE. Twenty postnatal day 19-20 rat pups were subjected to FPI or sham injury and were subsequently housed in EE (17 days) or standard conditions. Brains were processed according to the Golgi-Cox method and were analyzed using dendritic density (Sholl) and dendritic branching analyses in frontal, parietal, and occipital cortices. Rearing in EE induced an increase in dendritic density, primarily within the occipital cortex. FPI induced an increase in dendritic density, primarily in regions remote from the injury site, namely contralateral parietal cortex and ipsilateral and contralateral occipital cortex. In injured animals subsequently housed in EE, FPI appeared to inhibit the experience-dependent dendritic density effects of EE. However, an unexpected enhancement of dendritic density was seen in the ipsilateral occipital cortex, indicating a unique response of this region based on its distance-specific sensitivity to injury-induced plasticity and its region-specific sensitivity to experience-dependent plasticity. These results suggest that dendritic changes mediate the anatomical and behavioral changes characteristic of impaired developmental plasticity following FPI, and that these changes are dependent on location within the cerebral cortex.

Correlated binocular activity guides recovery from monocular deprivation

Abstract: Monocular deprivation (MD) has much more rapid and severe effects on the ocular dominance of neurons in the primary visual cortex (V1) than does binocular deprivation1. This finding underlies the widely held hypothesis that the developmental plasticity of ocular dominance reflects competitive interactions for synaptic space between inputs from the two eyes2. According to this view, the relative levels of evoked activity in afferents representing the two eyes determine functional changes in response to altered visual experience. However, if the deprived eye of a monocularly deprived kitten is simply reopened, there is substantial physiological and behavioural recovery, leading to the suggestion that absolute activity levels, or some other non-competitive mechanisms, determine the degree of recovery from MD3, 4, 5, 6, 7. Here we provide evidence that correlated binocular input is essential for such recovery. Recovery is far less complete if the two eyes are misaligned after a period of MD. This is a powerful demonstration of the importance of cooperative, associative mechanisms in the developing visual cortex.

A developmental morphologist's perspective on plasticity

Abstract: This series of essays addresses plasticity from the perspective of developmental morphology. The first essay deals with the problem of distinguishing between plasticity and other types of ontogenetic variation. In a temporally varying environment, morphological plasticity may be expressed as the production of a succession of different metamers. However, even in a constant environment, plant metamers can vary dramatically, a phenomenon known as heteroblasty. Because heteroblasty and plasticity can yield similar patterns of ontogenetic variation, the two are often confounded in analyses of developmental plasticity. The second essay discusses the integration of plant phenotypic responses and finds that the evidence for integration is equivocal. The third section shows that developmental properties can constrain the expression of morphological plasticity. Developmental lags and the ‘epiphenotype problem’ are particularly important features for analyses of the evolution and expression of plasticity. Finally, in answer to the question of strategies for studying plasticity, I emphasize the need for research at multiple levels and for the inclusion of a historical or phylogenetic perspective.

A brain adaptation view of plasticity: is synaptic plasticity an overly limited concept?

Abstract: A view that is emerging is that the brain has multiple forms of plasticity that must be governed, at least in part, by independent mechanisms. This view is illustrated by: (1) the apparent separate governance of some non-neural changes by activity, in contrast to synaptic changes driven by learning; (2) the apparent independence of different kinds of synaptic changes that occur in response to the learning aspects of training; (3) the occurrence of separate patterns of synaptic plasticity in the same system in response to different task demands; and (4) apparent dissociations between behaviorally induced synaptogenesis and LTP. The historical focus of research and theory in areas ranging from learning and memory to experiential modulation of brain development has been heavily upon synaptic plasticity since shortly after the discovery of the synapse. Based upon available data, it could be argued that: (1) synaptic, and even neuronal, plasticity is but a small fraction of the range of changes that occur in response to experience; and (2) we are just beginning to understand the importance of these other forms of brain plasticity. Appreciation of this aspect of the brain's adaptive process may allow us to better understand the capacity of the brain to tailor a particular set of changes to the demands of the specific experiences that generated them.

Synaptic Plasticity in Drug Reward Circuitry

Abstract: Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.

Developmental plasticity in the cardiovascular system of fish, with special reference to the zebrafish.

Abstract: During development the circulatory system of vertebrates typically starts operating earlier than any other organ. In these early stages, however, blood flow is not yet linked to metabolic requirements of tissues, as is well established for adults. While the autonomic nervous system becomes functional only quite late during development, in the early stages control of blood flow appears to be possible by blood-borne and/or local hormones. This study presents methods based on video-imaging techniques and fluorescence microscopy to visualize cardiac activity, as well as the vascular bed of developing lower vertebrates, and tests the idea that environmental factors, such as hypoxia, may modify cardiac activity, or even the early formation of blood vessels in embryos and larvae. In zebrafish larvae, adaptations of cardiovascular activity to chronic hypoxia become visible shortly after hatching, and the formation of some blood vessels is enhanced under chronic hypoxia. Exposure of early larval stages of zebrafish to a constant water current induces physiological adaptations, resulting in enhanced swimming efficiency and increased tolerance towards hypoxia. Furthermore, application of hormones such as NO can modify cardiac activity as well as peripheral resistance, and they can stimulate blood vessel formation. In consequence, even during early development of fish or amphibian larvae, the performance of cardiac muscle and of skeletal muscle can be modified by environmental influences and peripheral resistance can be adjusted. Even blood vessel formation can be stimulated by hypoxia, for example, or by the presence of specific hormones. Thus, at approximately the time of hatching the physiological performance of vertebrate larvae is already determined by the combined action of environmental influences and of genetic information.

Lineage plasticity and commitment in T‐cell development

Abstract: The earliest stages of intrathymic T-cell development include not only the acquisition of T-cell characteristics but also programmed loss of potentials for B, natural killer, and dendritic cell development. Evidence from genetics and cell-transfer studies suggests an order and some components of the mechanisms involved in loss of these options, but some of the interpretations conflict. The conflicts can be resolved by a view that postulates overlapping windows of developmental opportunity and individual mechanisms regulating progression along each pathway. This view is consistent with molecular evidence for the expression patterns of positive regulators of non-T developmental pathways, SCL, PU.1 and Id2, in early thymocytes. To some extent, overexpression of such regulators redirects thymocyte development in vitro. Specific commitment functions may normally terminate this developmental plasticity. Both PU.1 overexpression and stimulation of ectopically expressed growth factor receptors can perturb T- and myeloid/dendritic-cell divergence, but only in permissive stages. A cell-line system that approximates DN3-stage thymocytes reveals that PU.1 can alter specification even in a homogeneous population. However, the response of the population to PU.1 is sharply discontinuous. These studies show a critical role for regulatory context in restricting plasticity, which is probably maintained by interacting transcription factor networks.

Lesion-induced thalamocortical axonal plasticity in the S1 cortex is independent of NMDA receptor function in excitatory cortical neurons.

Abstract: Neural activity plays an important role in refinement and plasticity of synaptic connections in developing vertebrate sensory systems. The rodent whisker-barrel pathway is an excellent model system to investigate the role of activity in formation of patterned neural connections and their plasticity. When whiskers on the snout or the sensory nerves innervating them are damaged during a critical period in development, whisker-specific patterns are altered along the trigeminal pathway, including the primary somatosensory (S1) cortex. In this context, NMDA receptor (NMDAR)-mediated activity has been implicated in patterning and plasticity of somatosensory maps. Using CxNR1KO mice, in which NMDAR1 (NR1), the essential NMDAR subunit gene, is disrupted only in excitatory cortical neurons, we showed that NMDAR-mediated activity is essential for whisker-specific patterning of barrel cells in layer IV of the S1 cortex. In CxNR1KO mice, thalamocortical axons (TCAs) representing the large whiskers segregate into rudimentary patches, but barrels as cellular modules do not develop. In this study, we examined lesion-induced TCA plasticity in CxNR1KO mice. TCA patterns underwent normal structural plasticity when their peripheral inputs were altered after whisker lesions during the critical period. The extent of the lesion-induced morphological plasticity and the duration of the critical period were quantitatively indistinguishable between CxNR1KO and control mice. We conclude that TCA plasticity in the neocortex is independent of postsynaptic NMDAR activity in excitatory cortical neurons, and that non-NMDAR-mediated cortical activity and/or subcortical mechanisms must be operational in this process.

Rate and timing in cortical synaptic plasticity.

Abstract: Debate has raged over the past few years as to whether cortical neurons transmit information primarily in their average firing rates or in the precise timing of their spikes. Here, we address the related question of which features of spike trains control plasticity at cortical synapses. Using paired recording in slices we have developed a quantitative and predictive description of the joint dependence of cortical plasticity on the rate and relative timing of pre– and postsynaptic firing. The results hold important implications for which parts of the neural code are most readily stored for later retrieval.

Adaptation of Inputs in the Somatosensory System

Abstract: This chapter summarizes evidence that cortical maps and cortical response properties are in a permanent state of use-dependent fluctuations, where ‘‘use’’ includes trainingand learning-induced changes. In their simplest form, usedependent changes are input driven. Although attention and other high-level processes may contribute and enhance use-dependent neural changes by specific pathways conveying top-down information, reorganization can occur in the absence of high-level processes. The current experimental data imply that altered performance is based on altered forms of neural representations, and that all forms of perceptual learning can therefore be assumed to operate within the framework of cortical adaptivity. 2.1 Introductory Remarks 2.1.1 Two Forms of Plasticity Postontogenetic plasticity describes the capacity of adult brains to adapt to internal or environmental changes. It is useful to distinguish between two different forms of adult plasticity: 1. Lesion-induced plasticity, which subsumes cortical reorganization after injury or lesion, induced either centrally or at the periphery, refers to compensation for and repair of functions acquired before the injury or lesion. 2. Trainingand learning-induced plasticity, often called ‘‘use-dependent plasticity,’’ refers to plastic changes that parallel the acquisition of perceptual and motor skills. Because, for example, amputation changes the pattern of use entirely, a more accurate distinction would be between ‘‘lesion-induced’’ and ‘‘nonlesion-induced’’ plasticity. To what extent the two forms are based on di¤erent or perhaps even on similar mechanisms is a matter of ongoing debate. In contrast to developmental plasticity, adaptations of adult brains do not rely on maturation or growth. For learning-induced alterations, there is agreement on the crucial role played by so-called functional plasticity based on rapid and reversible modifications of synaptic e‰cacy, although largescale amputations have been shown to involve sprouting and outgrowth of a¤erent connections into neighboring regions at cortical and subcortical levels (Florence, Taub, and Kaas 1998; Jain et al. 2000). 2.1.2 Sites of Changes Perceptual learning is often highly specific to stimulus parameters such as the location or orientation of a stimulus, with little generalization of what is learned to other locations or to other stimulus configurations (see chapters 9, 11, 12, 14). Selectivity and locality of this type implies that the underlying neural changes are most probably occurring within early cortical representations that contain well-ordered topographic maps to allow for this selectivity (see chapter 1). In addition, a transfer of the newly acquired abilities is often considered an important marker of the processing level at which changes are most likely occur: limited generalization is taken as evidence for high locality of e¤ects in early representations. In contrast, transfer of learned abilities is taken as evidence for the involvement of higher processing levels often observed in task and strategy learning (see chapters 13, 14). There is increasing evidence that changes in early cortical areas might be more directly linked to perceptual learning than previously thought (Karni and Sagi 1991; Recanzone, Jenkins, et al. 1992; Schoups, Vogels, and Orban 1995; Crist et al. 1997; Fahle 1997, chapter 10). In fact, most of what we know today about adaptation of the somatosensory system comes from the investigation of the somatosensory areas characterized by extended and ordered neural representations of the body surface (box 2.1). In contrast, less is known about both the role of higher areas and the interaction between sensory association areas for perceptual learning. In any case, the conjecture that perceptual learning a¤ects early areas provides an important conceptual link to somatosensory adaptational processes (see chapters 9–14). 2.1.3 Driving Forces That Lead to Adaptational Changes What factors might induce changes in neural representations? Let us assume a dynamically maintained steady state of representations emerging from learning during development and adulthood that reflects the adaptation history to a ‘‘mean environment,’’ defined as the accumulated and idiosyncratic experience of an individual. Adaptational processes are assumed to operate on these representations, and long-lasting changes are likely to occur when sensory input patterns are altered such that they deviate from the mean environment. The average steady state can be altered in three principal ways: 1. By changing the input statistics. Specifically effective in driving adaptational changes are simultaneity, repetition, and, more generally, spatiotemporal proximity (see chapters 14, 20). Because these changes in input do not involve attention or processing for meaning, they induce a class of noncognitive adaptations based largely on bottom-up processing. 2. By drawing attention to certain aspects of a stimulus, thereby selecting it in comparison to others. The relevance of a stimulus can also change, depending on context, history, and behavioral task, thereby modifying how physically defined attributes are processed. There is general agreement that modification of early sensory processing by attention and stimulus relevance reflects top-down influences arising from cognitive processes (see chapters 13, 14, 20). 3. By using reward or punishment to reinforce learning. Such influences usually accelerate adaptational processes and are assumed to be mediated by specific brain regions modifying early sensory processing (see chapter 20). 2.1.4 The Hebbian Metaphor A central paradigm in the description and analysis of cortical plasticity is built around the Hebbian concept (1949): episodes of high temporal correlation between preand postsynaptic activity are prerequisite for inducing changes in synaptic e‰cacy. Historically, the idea that cooperative processes are crucially involved in generating long-lasting changes in excitability can be traced back to the nineteenth century ( James 1890). Indeed, since Hebb, the aspect of simultaneity has become a metaphor in neural plasticity, although the exact role of Hebbian mechanisms in use-dependent plasticity remains controversial (Carew et al. 1984; Fox and Daw 1993; Granger et al. 1994; Montague and Sejnowski 1994; Joublin et al. 1996; Buonomano and Merzenich 1996; Edeline 1996; Cruikshank and Weinberger 1996a,b; Ahissar et al. 1998). It has been suggested that the definition of Hebbian mechanisms 20 Hubert R. Dinse and Michael M. Merzenich

Consequences of the inherent developmental plasticity of organ and tissue relations

Abstract: Varied cell lineages, random elements of stomata and vein patterns, and unpredictable details of branch relations are all examples of evidence for an inherent plasticity of development that need not be dependent on environmental cues Such plastic form could be generated by a combination of programs and ‘Developmental Selection’, a principle that resembles Darwinian processes, albeit without genetic differences Both internal and environmental cues could act by modifying the outcome of this selection Adaptive responses to environmental heterogeneity cannot be strictly separated from the underlying plasticity of unperturbed development The proximal mechanisms and the genetic specification of the outcome of developmental selection require an excess developmental potential, one that includes many unused alternatives The choice between these alternatives depends on preset hierarchies, but this choice can be perturbed according to the environment as well as the internal conditions, including the ones due to random developmental mistakes Form is specified as a balance between signals of the various components of the organism, without a strict determination of their precise numbers and locations This requires that developing tissues and organs ‘inform’ the plant about their states and respond according to the signals and substrates they receive Further, the varied responses must be integrated so as to form and maintain an organized, functional whole Unexpected and unrecognized traits of known hormones, and especially auxin, suggest concrete knowledge about such mechanisms Plasticity that is based on developmental selection allows plants in a community to adjust their individual forms to those of their close neighbors It could have important evolutionary consequences: mutations that have favorable effects on one process could be accommodated by plastic adjustments of other parts of the functional plant On the other hand, genetic information required only for unusual conditions could be expected to deteriorate because it is not in constant use, and in fact plasticity that requires such is at best rare At the conceptual level, plasticity calls for integrating reductionist and organismal thinking A greater challenge is for the concurrent consideration of both proximal and Darwinian mechanisms

Activity-dependent synaptic plasticity: insights from neuromuscular junctions.

Abstract: Experience-dependent editing shapes synaptic connections throughout the developing nervous system, but the underlying cellular mechanisms remain poorly understood. A useful model synapse for addressing these mechanisms is the neuromuscular junction, the connection between spinal motor neurons and skeletal muscle fibers. Here the authors review current ideas about the role of activity in editing neuromuscular synaptic connections. A variety of new tools are being used to address some unanswered questions in vivo and in vitro. Understanding activity-dependent plasticity at developing neuromuscular synapses may reveal how neural circuits in the central nervous system are altered by experience throughout life.

Stability and plasticity of wild-type and Pax5-deficient precursor B cells.

Abstract: In Pax5-deficient mice, B cell development is blocked at the pre-BI cell stage. Like wild-type, Pax5 - / - pre-BI cells can be grown longterm in vitro in the presence of stromal cells and IL-7. However, unlike their wild-type in vitro-grown counterparts, Pax5 - / - pre-BI cells possess an extraordinary developmental plasticity showing hematopoietic stem cell features such as multipotency and self renewing capacity. Here we review and discuss this in vitro and in vivo plasticity of Pax5 - / - pre-BI cells.