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Showing papers in "Annual Review of Neuroscience in 1995"


Journal ArticleDOI
TL;DR: The two basic phenomena that define the problem of visual attention can be illustrated in a simple example and selectivity-the ability to filter out un­ wanted information is illustrated.
Abstract: The two basic phenomena that define the problem of visual attention can be illustrated in a simple example. Consider the arrays shown in each panel of Figure 1. In a typical experiment, before the arrays were presented, subjects would be asked to report letters appearing in one color (targets, here black letters), and to disregard letters in the other color (nontargets, here white letters). The array would then be briefly flashed, and the subjects, without any opportunity for eye movements, would give their report. The display mimics our. usual cluttered visual environment: It contains one or more objects that are relevant to current behavior, along with others that are irrelevant. The first basic phenomenon is limited capacity for processing information. At any given time, only a small amount of the information available on the retina can be processed and used in the control of behavior. Subjectively, giving attention to any one target leaves less available for others. In Figure 1, the probability of reporting the target letter N is much lower with two accompa­ nying targets (Figure la) than with none (Figure Ib). The second basic phenomenon is selectivity-the ability to filter out un­ wanted information. Subjectively, one is aware of attended stimuli and largely unaware of unattended ones. Correspondingly, accuracy in identifying an attended stimulus may be independent of the number of nontargets in a display (Figure la vs Ie) (see Bundesen 1990, Duncan 1980).

7,642 citations


Journal ArticleDOI
TL;DR: The mammalian visual system is endowed with a nearly infinite capacity for the recognition of patterns and objects, but to have acquired this capability the visual system must have solved what is a fundamentally combinatorial prob­ lem.
Abstract: The mammalian visual system is endowed with a nearly infinite capacity for the recognition of patterns and objects. To have acquired this capability the visual system must have solved what is a fundamentally combinatorial prob­ lem. Any given image consists of a collection of features, consisting of local contrast borders of luminance and wavelength, distributed across the visual field. For one to detect and recognize an object within a scene, the features comprising the object must be identified and segregated from those comprising other objects. This problem is inherently difficult to solve because of the combinatorial nature of visual images. To appreciate this point, consider a simple local feature such as a small vertically oriented line segment placed within a fixed location of the visual field. When combined with other line segments, this feature can form a nearly infinite number of geometrical objects. Any one of these objects may coexist with an equally large number of other

3,198 citations


Journal ArticleDOI
TL;DR: Because in vitro culture conditions are unlikely to provide all of the factors necessary for inducing the proliferation and differentiation of neural precursors, recent studies have explored the properties of well-characterized precursor populations after implantation back into specific regions of the developing or adult CNS.
Abstract: The nervous system of adult mammals, unlike the rest of the organs in the body, has been considered unique in its apparent inability to replace neurons following injury. However, in certain regions of the brain, neurogenesis occurs postnatally and continues through adulthood. The nature, fate, and longevity of cells undergoing proliferation within the CNS are unknown. These cells are increasingly becoming the focus of intense scrutiny; this is a recent development that has led to considerable controversy over the appropriate terminology to describe neural cells as they pass through different stages of proliferation, migration, and differentiation. Continuing studies detailing the properties of mitotic populations in the adult CNS will provide a better understanding of the nature of these cells during their development and should lead to a more consistent nomenclature. Studies of neural precursors isolated from the embryonic brain have indicated that many subgroups of cells undergo mitosis and subsequent differentiation into neurons and glia in vitro. A number of substances, such as growth factors and substrate molecules, are essential for these processes and also for lineage restriction and fate determination of these cells. Recent studies have shown that cells with proliferative capabilities can also be isolated from the adult brain. The nature of these cells is unknown, but there is evidence that both multipotent cells (stem cells) and lineage-restricted cells (neuroblasts or glioblasts) are resident within the mature CNS and that they can be maintained and induced to divide and differentiate in response to many of the same factors that influence their embryonic counterparts. Presently, it is unclear how many potentially quiescent precursor cells exist in the adult brain or what combination of growth factors and substrate molecules is involved in the proliferation and differentiation of these cells. Some of these questions are currently being addressed by using immortalized neural precursors or growth factor-expanded populations of primary precursors to model precursor responsiveness to environmental manipulations. Because in vitro culture conditions are unlikely to provide all of the factors necessary for inducing the proliferation and differentiation of neural precursors, recent studies have explored the properties of well-characterized precursor populations after implantation back into specific regions of the developing or adult CNS. These studies have highlighted the importance of the microenvironment in precursor differentiation and further suggested that precursor plasticity is a characteristic that is probably common to neural precursors throughout the CNS.(ABSTRACT TRUNCATED AT 400 WORDS)

897 citations


Journal ArticleDOI
TL;DR: The number of neurons in the adult nervous system and the density of innervation of their targets are determined by a competitive process in which tissues produce trophic factors that support neuronal survival.
Abstract: Hypothesis Programmed neuronal cell death is a prominent feature of vertebrate embryonic development. Timing and extent of cell death are dependent on the influence of the targets those neurons innervate, The number of neurons in the adult nervous system and the density of innervation of their targets are determined by a competitive process in which tissues produce, in limiting quantities, trophic factors that support neuronal survival. Neurons actively compete to establish optimum contact with the target, and those making the least effective contacts with the target are eliminated by cell dea th. If each target of inner­ vation elaborated a unique trophic factor, the resulting mechanism would provide a means of enforcing the correct patterns of connectivity between

842 citations


Journal ArticleDOI
TL;DR: Drug reinforcement is a form of behavioral plasticity in which behavioral changes occur in response to acute exposure to a reinforcing drug, and the addicted state are both characterized by an increase in drug-seeking behavior.
Abstract: Drug reinforcement is a form of behavioral plasticity in which behavioral changes occur in response to acute exposure to a reinforcing drug. Drugs are classified as reinforcers if the probability of a drug-seeking response is in­ creased when the response is temporally paired with drug exposure. Such rapid and powerful associations between a drug reinforcer and a drug-seeking re­ sponse probably reflect the drug's ability to directly modulate preexisting brain-reinforcement systems. These preexisting systems normally mediate the reinforcement produced by natural reinforcers such as food, sex, and social interaction. Upon acute exposure most abused drugs function as positive rein­ forcers, presumably because they produce a positive affective state (e.g. eu­ phoria). Chronic exposure to reinforcing drugs can lead to drug addiction, which is also characterized by an increase in drug-seeking behavior. Clinically, this sustained increase in drug-seeking behavior (Le. craving) is a core feature of drug addiction. However, unlike drug reinforcement in nonaddicted subjects, addicted subjects exhibit a sustained increase in drug-seeking behavior even when the drug is absent or withdrawn. In some of these situations drugs can function as negative reinforcers in that they offer relief from a negative affec­ tive state (e.g. dysphoria). Since acute drug reinforcement and the addicted state are both characterized by an increase in drug-seeking behavior, common

586 citations


Journal ArticleDOI
TL;DR: The cerebellum provides a unique system for studying CNS development, combining the three classic patterns of CNS development-morphogenetic movements, the formation of ganglionic struc­ tures, and the establishment of neuronal layers-within one brain region.
Abstract: The cerebellar cortex is one of the best-studied regions of the CNS. For nearly a century, all of the cerebellar cell types and the patterns of their synaptic connections have been known. Much of this wealth of information comes from Ramon y Cajal's work (1889, 1911, 1960) with Golgi studies. Further infor­ mation on the development (Altman & Bayer 1985a-c, Rakic 1971, Miale & Sidman 1961), anatomy (Palay & Chan-Palay 1974), fiber tracts (BrodaI1981), and circuitry (Llinas & Hillman 1969) of the cerebellar cortex has emerged over the past several decades. The cerebellum provides a unique system for studying CNS development, combining the three classic patterns of CNS development-morphogenetic movements, the formation of ganglionic struc­ tures, and the establishment of neuronal layers-within one brain region. Remarkably simple in its basic plan, the adult cerebellar cortex contains only three layers and two principal classes of neurons. The abundance of one of these principal neurons, the granule cell, has enabled detailed analyses of the molecular mechanisms that underlie the basic steps in neuronal differentiation and has pointed out the role of local community factors in CNS neuronal development. Moreover, studies of naturally occurring mutations (Heintz et al 1993, Sidman 1968) and of targeted gene disruptions that block discrete steps in the development of this region (McMahon 1993, Joyner & Hanks 1991,

555 citations


Journal ArticleDOI
TL;DR: The purpose of the present review is to examine the opposite phenomenon, use-dependent long-lasting decreases in synaptic strength, which have been collectively termed long-term synaptic depression (LTD).
Abstract: It is widely assumed that long-term changes in synaptic strength underlie information storage in the brain and, ultimately, behavioral memory. Recent years have seen a major effort to identify and analyze electrophysiological model systems in which particular patterns of neural activity give rise to such enduring changes. Most of this attention has been focused upon hippocampal long-term synaptic potentiation (LTP), in which brief activation of a set of afferents gives rise to a persistent increase in synaptic strength of the activated synapses. LTP is a broad term. It has come to mean any persistent increase in synaptic strength induced by a variety of mechanisms in a large number of locations in the nervous system. The purpose of the present review is to examine the opposite phenomenon, use-dependent long-lasting decreases in synaptic strength, which have been collectively termed long-term synaptic depression (LTD). Also a blanket term, LTD denotes depression induced according to a variety of synaptic modification rules, mediated by various electrophysiological and biochemical events, and occurring extensively in the nervous system.

509 citations


Journal ArticleDOI
TL;DR: This chapter reviews contemporary findings concerning the dynamic regulation of receptive fields and maps in the primary auditory, somatosensory, and visual cortices of the adult brain and provides a framework that will be useful for thinking about both current and future research on adult sensory cortical plasticity and reorganization.
Abstract: A dominant belief in neuroscience is that sensory systems in the adult are stable, in contrast to the extensive and pervasive plasticity that characterizes development of the nervous system. Empirical bases for this dogma of sensory immutability include the usually precise and stable responses of sensory neurons in anesthetized animals and the reduction of sensory cortical plasticity beyond critical periods of development. The subjective experience of neuro-scientists also supports the dogma. Perception of the outside world appears to be clear, immediate and effortless. To most workers, this implies that the sensory systems, once having developed, must be stable in order to provide accurate information about the environment. However, a rapidly growing literature attests to a very large degree of short- and long-term modification of receptive fields (RF) and reorganization of representational maps under variety of circumstances: learning, sensory stimulation, and sensory deafferentation. This chapter reviews contemporary findings concerning the dynamic regulation of receptive fields and maps in the primary auditory, somatosensory, and visual cortices of the adult brain. In contrast to previous reviews that have been confined largely to the perspective of sensory physiology, this article also emphasizes behavioral considerations. This seems to be appropriate, if not mandatory, because behavior is normally dynamic and adaptive, and sensory cortex is notable for its evolutionary development and implication in higher functions. The present coverage is highly selective, necessitated by severe constraints of space. Detailed analyses of publications were not possible and coverage of the effects of sensory deafferentation had to be limited to a scant summary of major effects and their possible relevance to sensory stimulation and learning; fortunately the effects of deafferentation have been reviewed in detail (Kaas 1991). Within the literature on sensory stimulation and learning, studies limited to standard learning paradigms were not included, in favor of studies of receptive fields and representational maps. These limitations should not unduly compromise this review because its intention is mainly conceptual. Specifically, the goal is to provide a framework that will be useful for thinking about both current and future research on adult sensory cortical plasticity and reorganization. This framework is based on an empirical law that is not yet widely appreciated in neuroscience. It may be summarized as follows: Behaving (i.e. waking) animals can continually acquire and retain information about (a) individual sensory stimuli, (b) relationships between various sensory stimuli, and (c) relationships between their own behavior and its sensory consequences. An implication of this law is that the attainment of an adequate understanding of how sensory cortex in the adult subserves perception and behavior also requires achieving an adequate account of the role of learning in sensory cortex. In theory, this role could have been nil. In fact it is not, as attested by the results of explicit learning experiments and other studies that can reasonably be considered to involve learning. The role of learning in denervation-induced plasticity and reorganization is currently largely conjectural but cannot be discounted. The following topics are discussed in turn: the relationship between sensory physiology and learning, basic forms of learning that are particularly relevant to adult cortical plasticity, methodological considerations, major issues and emerging principles in learning and sensory cortex, examples of these principles from the literature on learning, brief comments on the effects of sensory deafferentation, and conclusions.

325 citations


Journal ArticleDOI
TL;DR: A prerequisite for understanding learning and memory is to elevate specific mechanisms of cellular plasticity into cellular mechanisms of learning by establishing their function in the context of a neural system that mediates learning andMemory in a particular behavior.
Abstract: Studies of the neural basis of learning and memory in intact animals must, by their nature, start "from the top" by choosing a behavior that can be modified through learning, revealing how iaeuronal activity gives rise to that behavior, and then investigating, in the awake, behaving animal, changes in neural signaling that are associated with learning. Such studies also must recognize that the learning and memory expressed in the behavior of an animal will reflect both the properties of the neural network that mediates the behavior and the nature of the underlying changes in the operation of cells or synapses. In the past 10 years, there has been an explosion of information about learning and memory in the vestibulo-ocular reflex (VOR) of the awake, behaving monkey. At the same time, there have been unprecedented advances in understanding mechanisms of cellular plasticity such as long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. A prerequisite for understanding learning and memory is to elevate specific mechanisms of cellular plasticity into cellular mechanisms of learning by establishing their function in the context of a neural system that mediates learning and memory in a particular behavior. Our review synthesizes the

244 citations


Journal ArticleDOI
TL;DR: The significance of neuromorphic systems is that they offer a method of exploring neural computation in a medium whose physical behavior is analogous to that of biological nervous systems and that operates in real time irrespective of size.
Abstract: Neuromorphic systems emulate the organization and function of nervous systems. They are usually composed of analogue electronic circuits that are fabricated in the complementary metal-oxide-semiconductor (CMOS) medium using very large-scale integration (VLSI) technology. However, these neuromorphic systems are not another kind of digital computer in which abstract neural networks are simulated symbolically in terms of their mathematical behavior. Instead, they directly embody, in the physics of their CMOS circuits, analogues of the physical processes that underlie the computations of neural systems. The significance of neuromorphic systems is that they offer a method of exploring neural computation in a medium whose physical behavior is analogous to that of biological nervous systems and that operates in real time irrespective of size. The implications of this approach are both scientific and practical. The study of neuromorphic systems provides a bridge between levels of understanding. For example, it provides a link between the physical processes of neurons and their computational significance. In addition, the synthesis of neuromorphic systems transposes our knowledge of neuroscience into practical devices that can interact directly with the real world in the same way that biological nervous systems do.

231 citations


Journal ArticleDOI
TL;DR: There is clear evidence for the existence of two types of cues that collaborate to direct growth--short-range cues that can direct axons along the edge of the spinal cord and a long-range chemoattractant secreted by the floor plate cells whose main function may be to direct later-extending commissural axons that must migrate through the complex environment of the developing motor column.
Abstract: The data reviewed above have implicated the floor plate in directing axonal growth towards the midline, in directing the behavior of axons at the midline, and finally, in directing the longitudinal growth of axons alongside the midline. In the case of growth to the midline, there is clear evidence for the existence of two types of cues that collaborate to direct growth--short-range cues that can direct axons along the edge of the spinal cord and a long-range chemoattractant secreted by the floor plate cells whose main function may be to direct later-extending commissural axons that must migrate through the complex environment of the developing motor column. Determining the precise contribution of these cues will require identifying them and perturbing them in vivo. The cues that direct growth along the edge are unknown; their identification in the spinal cord would be of quite general significance, since the growth of axons parallel to (but not in contact with) the pial surface is a widespread feature of early axon growth at all axial levels of the neural tube. A strong candidate for the long-range chemoattractant is netrin-1, a homologue of the UNC-6 protein of C. elegans and a distant relative of laminin, which is expressed by floor plate cells and which can both promote and orient commissural axon outgrowth. Netrin-1 may also influence growth of other populations of neurons that exhibit stereotyped behaviors near the ventral midline. Much less is known about the exact role of the floor plate in directing axon growth at the midline, though it is clearly required for accurate guidance. In the absence of the floor plate, a range of errors has been found, the most prominent of which are aberrant midline crossings and errors in longitudinal growth near the ventral midline. The severity of these errors varies with species, which could result from either the variable importance of the floor plate in the different species or the fact that, so far, quite different manipulations of the ventral midline region have been performed in different species. The most specific perturbation of the ventral midline occurs in the zebrafish cyc-1 mutant, where the selective loss of the floor plate leads to stereotyped misrouting events. Perhaps surprisingly, virtually all axons that grow to the midline turn longitudinally (although sometimes in the wrong direction).(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: This work focuses on agrin, which is likely to play a central role in signaling and regulating the differentiation of the postsynaptic apparatus at the neuro­ muscular junction, and discusses the mounting evidence suggesting an analogous role for agrin in the CNS.
Abstract: The precise, rapid, and ordered communication between neurons and their targets is the distinguishing characteristic of the nervous system. Chemical synapses are the primary locus of this information exchange, and the structural and molecular specializations essential for their proper functioning are under­ stood in considerable detail (reviewed in Jessell & Kandel 1993, Stevens 1993). In contrast, much less is known about how synaptic structure is regulated during development and regeneration. Such structural changes may also me­ diate important aspects of synaptic plasticity in learning and memory (Bliss & Collingridge 1993, Lisman & Harris 1993). Most of our knowledge of synaptogenesis has come from studying the neuromuscular junction. A search for the mechanisms underlying differentia­ tion at this synapse has focussed on three molecular systems: the cytoskeleton and its associated membrane proteins, trophic factors, and a specific extracel­ lular matrix component, agrin. Recent reviews have dealt with the overall process of synaptogenesis and with the contribution of the cytoskeleton and trophic factors (Salpeter 1987, Falls et al 1993, Froehner 1993, Hall & Sanes 1993). Here we focus on agrin, which is likely to play a central role in signaling and regulating the differentiation of the postsynaptic apparatus at the neuro­ muscular junction (Nastuk & Fallon 1993). In addition, we also discuss the mounting evidence suggesting an analogous role for agrin in the CNS.


Journal ArticleDOI
TL;DR: Recent advances in the study of phototransduction in the eye of the fruit fly Drosophila melanogaster have provided new insights into the molecular mechanisms, and these are discussed in the context of existing models for photo­ transduction.
Abstract: The ability to sense and to react to environmental stimuli is crucial for the survival of any organism. The primary event in sensory information processing is the transduction of external signals by specialized neurons into the electrical code that forms the input to processing centers in the brain. In the retina, photoreceptor neurons transduce the absorption rate of photons into a graded change in the ionic permeabilites of the cell membrane in a process known as phototransduction. Photoreceptor cells demonstrate beautiful properties of high sensitivity, rapid response kinetics, and broad dynamic response range that allow for efficient signal detection over a wide variety of light intensities. How are these properties encoded by the signal transduction machinery? The answer to this question is as yet incomplete, but recent advances in the study of phototransduction in the eye of the fruit fly Drosophila melanogaster have provided new insights into the molecular mechanisms. The goal of this review is to discuss these new advances in the context of existing models for photo­ transduction. Phototransduction offers several advantages as a model system for the study of cellular signal transduction in general. First, photoreceptor cells are readily accessible for experimentation, and genetic, biochemical, and electrophysio­ logical techniques for studying photoreceptor function have been well de­ scribed (Zuker 1992). Second, functional constraints imposed by the dynamic nature of the visual input have forced the evolution of signaling mechanisms 283


Journal ArticleDOI
TL;DR: The integration of visual and auditory spatial information that underlies the localization of stimulus sources is discussed as an example of integrative processes that lead to complex stimulus selectivity of high-order neurons.
Abstract: The accurate and reliable perception of complex stimuli requires the integration of information provided by a variety of sensory cues. For example, the perception of a face involves the integration of shape, depth, color, and texture. Within the nervous system, the representation of complex stimuli results from both analytic and synthetic processes. First, complex stimuli are analyzed into their constituent components by low-order sensory neurons that are selective for simple stimulus features. Then, increasingly complex stimulus selectivities are synthesized by combining the selectivities of appropriate lower-order neurons (Knudsen et al 1987, Van Essen et al 1992). At the highest levels in such sensory hierarchies, neurons may be selective for stimuli that have unique significance for the individual (Margoliash 1986, Miyashita 1988), indicating that experience may play a critical role in establishing the response properties of such high-order neurons. Although much progress has been made in understanding how sensory systems analyze stimuli into constituent features, much less is known about how information is recombined across features to create selectivity for complex stimuli. This article discusses the integration of visual and auditory spatial information that underlies the localization of stimulus sources as an example of integrative processes that lead to complex stimulus selectivity of high-order neurons. The brain derives great advantage from combining visual and auditory

Journal ArticleDOI
TL;DR: Early infantile autism is the most severe of a group of neurodevelopmental syndromes called the pervasive developmental disorders as discussed by the authors, and the onset of autistic signs and behaviors typically occurs in infancy, and the syndrome usually fully present by the fourth year.
Abstract: Early infantile autism is the most severe of a group of neurodevelopmental syndromes called the pervasive developmental disorders. The clinical features of autism vary greatly, but, by definition, include deficits in social relatedness, communication, and interests or routines. The onset of autistic signs and behaviors typ ically occurs in infancy, and the syndrome is usually fully present by the fourth year. The presence of mental retardation affects the clinical picture greatly. Severely autistic children may be retarded and mute and are often preoccupied with repetitive activities; they often exhibit motor stereotypes, such as rocking or hand flapping. They can be profoundly withdrawn and may show extreme aversion to social or physical contact. More mildly affected children may have normal or even superior intelligence, with well-developed language skills. Their deficits in social relatedness and preoccupation with rituals and routines may set them apart as very odd, but not necessarily as autistic. Au...


Journal ArticleDOI
TL;DR: There is good reason to believe X-linked loci contribute significantly to this gender inequity and as many as 95 genes have been tentatively assigned to the X chromosome where mutations lead to mental retardation as at least part of the phenotype.
Abstract: INTRODUCTION Mental retardation represents a deficiency in intelligence, as measured by IQ, with limited adaptive behavior that is normally reflected in maturation, learn­ing, or social adjustment (American Psychiatric Association 1987). Approxi­mately 1 to 3% of the population, depending upon definitions of adaptive behavior, is mentally retarded (Popper 1988). The etiologies and determinants of mental retardation are diverse and include socioeconomic influences leading to extreme malnutrition and/or inadequate prenatal care; toxic insults, such as that leading to fetal alcohol syndrome; trauma and infection; and genetic factors (Popper 1988). At least 300 genetic disorders include mental retardation as part of the phenotype, and genetic components are considered important influences on related disorders such as attention deficit disorder and learning disability (Smith et al 1983, Biederman et al 1987, McKusick et al 1992). Since the early twentieth century a male predominance at all levels of mental retardation, ranging from 1.5 to 3 times the incidence in females, has been acknowledged (Penrose 1938). Although a variety of explanations have been put forth, including the probable ascertainment bias of mentally retarded males being more frequently institutionalized because of uncontrollable or violent behavior, there is good reason to believe X-linked loci contribute significantly to this gender inequity (Opitz 1986). Perhaps as many as 95 genes have been tentatively assigned to the X chromosome where mutations lead to mental retardation as at least part of the phenotype (Schwartz 1993). As the vast