Showing papers in "Annual Review of Neuroscience in 2002"
TL;DR: The growing literature that supports a critical role for AMPA receptors trafficking in LTP and LTD is reviewed, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins.
Abstract: Activity-dependent changes in synaptic function are believed to underlie the formation of memories. Two prominent examples are long-term potentiation (LTP) and long-term depression (LTD), whose mechanisms have been the subject of considerable scrutiny over the past few decades. Here we review the growing literature that supports a critical role for AMPA receptor trafficking in LTP and LTD, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins. While much work remains to understand the molecular basis for synaptic plasticity, recent results on AMPA receptor trafficking provide a clear conceptual framework for future studies.
2,587 citations
TL;DR: Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.
Abstract: Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.
1,637 citations
TL;DR: Three lines of fMRI research into how the semantic system is organized in the adult brain are discussed, which broaden the understanding of how the brain stores, retrieves, and makes sense of semantic information and challenge some commonly held notions of functional modularity in the language system.
Abstract: ▪ Abstract Until recently, our understanding of how language is organized in the brain depended on analysis of behavioral deficits in patients with fortuitously placed lesions. The availability of functional magnetic resonance imaging (fMRI) for in vivo analysis of the normal brain has revolutionized the study of language. This review discusses three lines of fMRI research into how the semantic system is organized in the adult brain. These are (a) the role of the left inferior frontal lobe in semantic processing and dissociations from other frontal lobe language functions, (b) the organization of categories of objects and concepts in the temporal lobe, and (c) the role of the right hemisphere in comprehending contextual and figurative meaning. Together, these lines of research broaden our understanding of how the brain stores, retrieves, and makes sense of semantic information, and they challenge some commonly held notions of functional modularity in the language system.
1,335 citations
TL;DR: The posterior parietal cortex (PPC), historically believed to be a sensory structure, is now viewed as an area important for sensory-motor integration, and among its functions is the forming of intentions, that is, high-level cognitive plans for movement.
Abstract: The posterior parietal cortex (PPC), historically believed to be a sensory structure, is now viewed as an area important for sensory-motor integration. Among its functions is the forming of intentions, that is, high-level cognitive plans for movement. There is a map of intentions within the PPC, with different subregions dedicated to the planning of eye movements, reaching movements, and grasping movements. These areas appear to be specialized for the multisensory integration and coordinate transformations required to convert sensory input to motor output. In several subregions of the PPC, these operations are facilitated by the use of a common distributed space representation that is independent of both sensory input and motor output. Attention and learning effects are also evident in the PPC. However, these effects may be general to cortex and operate in the PPC in the context of sensory-motor transformations.
1,233 citations
TL;DR: These findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.
Abstract: A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal periods, the presence of cognitive and behavioral signs during childhood and adolescence, and the lack of evidence of a neurodegenerative process in most individuals with schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest that no single gene or factor is responsible for driving a highly complex biological process. Together, these findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.
1,083 citations
TL;DR: This review focuses on the organization of interconnected limbic-hypothalamic pathways that participate in the neural control of reproduction and summarizes what is known about the developmental neurobiology of these pathways.
Abstract: Mammalian reproduction depends on the coordinated expression of behavior with precisely timed physiological events that are fundamentally different in males and females. An improved understanding of the neuroanatomical relationships between sexually dimorphic parts of the forebrain has contributed to a significant paradigm shift in how functional neural systems are approached experimentally. This review focuses on the organization of interconnected limbic-hypothalamic pathways that participate in the neural control of reproduction and summarizes what is known about the developmental neurobiology of these pathways. Sex steroid hormones such as estrogen and testosterone have much in common with neurotrophins and regulate cell death, neuronal migration, neurogenesis, and neurotransmitter plasticity. In addition, these hormones direct formation of sexually dimorphic circuits by influencing axonal guidance and synaptogenesis. The signaling events underlying the developmental activities of sex steroids involve interactions between nuclear hormone receptors and other transcriptional regulators, as well as interactions at multiple levels with neurotrophin and neurotransmitter signal transduction pathways.
687 citations
TL;DR: The overall organization of the peripheral autonomic nervous system has been known for many decades, but the mechanisms by which it is controlled by the central nervous system are just now coming to light.
Abstract: The overall organization of the peripheral autonomic nervous system has been known for many decades, but the mechanisms by which it is controlled by the central nervous system are just now coming to light. In particular, two major issues have seen considerable progress in the past decade. First, the pathways that provide visceral sensation to conscious perception at a cortical level have been elucidated in both animals and humans. The nociceptive system runs in parallel to the pathways carrying visceral sensation from the cranial nerves and may be considered in itself a component of visceral sensation. Second, structures in the central nervous system that generate patterns of autonomic response have been identified. These pattern generators are located at multiple levels of the central nervous system, and they can be combined in temporal and spatial patterns to subserve a wide range of behavioral needs.
662 citations
TL;DR: The role of Notch during gliogenesis in both fruit flies and vertebrates is examined, as well as evidence in vertebrates that some glia may be stem cells.
Abstract: The Notch signaling pathway has long been known to influence cell fate in the developing nervous system. However, this pathway has generally been thought to inhibit the specification of certain cell types in favor of others, or to simply maintain a progenitor pool. Recently, this view has been challenged by numerous studies suggesting that Notch may play an instructive role in promoting glial development. This work has inspired a new look at the role of Notch signaling in specifying cell fate. It has also prompted further consideration of the emerging view that in some contexts glia may be multipotent progenitors. This review examines the role of Notch during gliogenesis in both fruit flies and vertebrates, as well as evidence in vertebrates that some glia may be stem cells.
592 citations
TL;DR: Current evidence suggests that while ganglion cells have little influence on the differentiation of their hair cell targets, quite the opposite is true in the brain.
Abstract: The neurons of the cochlear ganglion transmit acoustic information between the inner ear and the brain. These placodally derived neurons must produce a topographically precise pattern of connections in both the inner ear and the brain. In this review, we consider the current state of knowledge concerning the development of these neurons, their peripheral and central connections, and their influences on peripheral and central target cells. Relatively little is known about the cellular and molecular regulation of migration or the establishment of precise topographic connection to the hair cells or cochlear nucleus (CN) neurons. Studies of mice with neurotrophin deletions are beginning to yield increasing understanding of variations in ganglion cell survival and resulting innervation patterns, however. Finally, existing evidence suggests that while ganglion cells have little influence on the differentiation of their hair cell targets, quite the opposite is true in the brain. Ganglion cell innervation and synaptic activity are essential for normal development of neurons in the cochlear nucleus.
558 citations
TL;DR: The actions of transcription factors within motor neuron progenitors, which initiate a cascade of transcriptional interactions that lead to motor neuron specification, are described and the downstream targets of the LIM code are discussed, especially in the context of subtype-specific motor axon pathfinding.
Abstract: The topographic assembly of neural circuits is dependent upon the generation of specific neuronal subtypes, each subtype displaying unique properties that direct the formation of selective connections with appropriate target cells. Studies of motor neuron development in the spinal cord have begun to elucidate the molecular mechanisms involved in controlling motor projections. In this review, we first describe the actions of transcription factors within motor neuron progenitors, which initiate a cascade of transcriptional interactions that lead to motor neuron specification. We next highlight the contribution of the LIM homeodomain (LIM-HD) transcription factors in establishing motor neuron subtype identity. Importantly, it has recently been shown that the combinatorial expression of LIM-HD transcription factors, the LIM code, confers motor neuron subtypes with the ability to select specific axon pathways to reach their distinct muscle targets. Finally, the downstream targets of the LIM code are discussed, especially in the context of subtype-specific motor axon pathfinding.
537 citations
TL;DR: Analysis of synapse abnormalities in patients and Fmr1 knockout mice should prove useful in studying the pathogenesis of fragile X syndrome and understanding learning and cognition in general.
Abstract: ▪ Abstract Fragile X syndrome is one of the most common forms of inherited mental retardation. In most cases the disease is caused by the methylation-induced transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene that occurs as a result of the expansion of a CGG repeat in the gene's 5′UTR and leads to the loss of protein product fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein that associates with translating polyribosomes as part of a large messenger ribonucleoprotein (mRNP) and modulates the translation of its RNA ligands. Pathological studies from the brains of patients and from Fmr1 knockout mice show abnormal dendritic spines implicating FMRP in synapse formation and function. Evidence from both in vitro and in vivo neuronal studies indicates that FMRP is located at the synapse and the loss of FMRP alters synaptic plasticity. As synaptic plasticity has been implicated in learning and memory, analysis of synapse abnormalities in patients and Fmr1 knockou...
TL;DR: It will be shown that the conjoint manipulation of bottom-up and top-up inputs to an area can be used to test for interactions between them, in elaborating cortical responses, and the prevalence of top-down influences and the plausibility of generative models of sensory brain function are pointed to.
Abstract: Unsupervised models of how the brain identifies and categorizes the causes of its sensory input can be divided into two classes: those that minimize the mutual information (i.e., redundancy) among evoked responses and those that minimize the prediction error. Although these models have the same goal, the way that goal is attained, and the functional architectures required, are fundamentally different. This review describes the differences, in the functional anatomy of sensory cortical hierarchies, implied by the two models. We then consider how neuroimaging can be used to disambiguate between them. The key distinction reduces to whether backward connections are employed by the brain to generate a prediction of sensory inputs. To ascertain whether backward influences are evident empirically requires a characterization of functional integration among brain systems. This review summarizes the approaches to measuring functional integration in terms of effective connectivity and proceeds to address the question posed by the theoretical considerations. In short, it will be shown that the conjoint manipulation of bottom-up and top-down inputs to an area can be used to test for interactions between them, in elaborating cortical responses. The conclusion, from these sorts of neuroimaging studies, points to the prevalence of top-down influences and the plausibility of generative models of sensory brain function.
TL;DR: The aim of this review is to describe and discuss the current knowledge regarding the hypocretin neurotransmitter system in narcolepsy and normal sleep.
Abstract: The hypocretins (orexins) are two novel neuropeptides (Hcrt-1 and Hcrt-2), derived from the same precursor gene, that are synthesized by neurons located exclusively in the lateral, posterior, and perifornical hypothalamus. Hypocretin-containing neurons have widespread projections throughout the CNS with particularly dense excitatory projections to monoaminergic centers such as the noradrenergic locus coeruleus, histaminergic tuberomammillary nucleus, serotoninergic raphe nucleus, and dopaminergic ventral tegmental area. The hypocretins were originally believed to be primarily important in the regulation of appetite; however, a major function emerging from research on these neuropeptides is the regulation of sleep and wakefulness. Deficiency in hypocretin neurotransmission results in the sleep disorder narcolepsy in mice, dogs, and humans. The hypocretins are also uniquely positioned to link sleep, appetite, and neuroendocrine control. The aim of this review is to describe and discuss the current knowledge regarding the hypocretin neurotransmitter system in narcolepsy and normal sleep.
TL;DR: This work reviews a number of recent studies that have used a context-based approach to explore the neuronal bases of visual scene perception and shows that neuronal sensitivity must be assessed in varied contexts that differentially influence perceptual interpretation.
Abstract: The visual image formed on the retina represents an amalgam of visual scene properties, including the reflectances of surfaces, their relative positions, and the type of illumination. The challenge facing the visual system is to extract the "meaning" of the image by decomposing it into its environmental causes. For each local region of the image, that extraction of meaning is only possible if information from other regions is taken into account. Of particular importance is a set of image cues revealing surface occlusion and/or lighting conditions. These information-rich cues direct the perceptual interpretation of other more ambiguous image regions. This context-dependent transformation from image to perception has profound-but frequently under-appreciated-implications for neurophysiological studies of visual processing: To demonstrate that neuronal responses are correlated with perception of visual scene properties, rather than visual image features, neuronal sensitivity must be assessed in varied contexts that differentially influence perceptual interpretation. We review a number of recent studies that have used this context-based approach to explore the neuronal bases of visual scene perception.
TL;DR: In the final phases of HIV or SIV infection, this chronic, widespread, and dramatic level of macrophage/monocyte/microglial activation constitutes a self-sustaining state of Macrophage dysregulation, which results in pathological alterations and the emergence of various neurological problems.
Abstract: This review focuses on the role of the extended macrophage/monocyte family in the central nervous system during HIV or SIV infection. The accumulated data, buttressed by recent experimental results, suggest that these cells play a central, pathogenic role in retroviral-associated CNS disease. While the immune system is able to combat the underlying retroviral infection, the accumulation and widespread activation of macrophages, microglia, and perivascular cells in the CNS are held in check. However, with the collapse of the immune system and the disappearance of the CD4(+) T cell population, productive infection reemerges, especially in CNS macrophages. These cells, as well as noninfected macrophages, are stimulated to high levels of activation. When members of this cell group become highly activated, they elaborate a wide spectrum of deleterious substances into the neural parenchyma. In the final phases of HIV or SIV infection, this chronic, widespread, and dramatic level of macrophage/monocyte/microglial activation constitutes a self-sustaining state of macrophage dysregulation, which results in pathological alterations and the emergence of various neurological problems.
TL;DR: It is suggested that extracellular signals play an important role in regulating every aspect of dendritic development and thereby exert a critical influence on cortical connectivity.
Abstract: Dendritic morphology has a profound impact on neuronal information processing. The overall extent and orientation of dendrites determines the kinds of input a neuron receives. Fine dendritic appendages called spines act as subcellular compartments devoted to processing synaptic information, and the dendritic branching pattern determines the efficacy with which synaptic information is transmitted to the soma. The acquisition of a mature dendritic morphology depends on the coordinated action of a number of different extracellular factors. Here we discuss this evidence in the context of dendritic development in the cerebral cortex. Soon after migrating to the cortical plate, neurons extend an apical dendrite directed toward the pial surface. The oriented growth of the apical dendrite is regulated by Sema3A, which acts as a dendritic chemoattractant. Subsequent dendritic development involves signaling by neurotrophic factors and Notch, which regulate dendritic growth and branching. During postnatal development the formation and stabilization of dendritic spines are regulated in part by patterns of synaptic activity. These observations suggest that extracellular signals play an important role in regulating every aspect of dendritic development and thereby exert a critical influence on cortical connectivity.
TL;DR: Recent technological breakthroughs allowing for large-scale analysis of gene transcripts and large- scale monitoring of the immune response with protein chips are revealing new participants in the pathogenesis of multiple sclerosis.
Abstract: Recent technological breakthroughs allowing for large-scale analysis of gene transcripts and large-scale monitoring of the immune response with protein chips are revealing new participants in the pathogenesis of multiple sclerosis. Some of these participants may be useful targets for therapy.
TL;DR: Three sources that produce neural cells closely resembling their normal counterparts are now available: oncogene immortalized stem cells, neurospheres, and embryonic stem cell (ES)-derived neural cells.
Abstract: Large-scale sources of neural stem cells are crucial for both basic research and novel approaches toward treating neurological disorders. Three sources that produce neural cells closely resembling their normal counterparts are now available: oncogene immortalized stem cells, neurospheres, and embryonic stem cell (ES)-derived neural cells. Cells including multiple subtypes of CNS and PNS neurons, as well as oligodendrocytes, Schwann cells, and astrocytes, are modeled by these large-scale sources. Although most cell lines were originally from rodents, their human counterparts are being discovered and characterized.
TL;DR: Progress in the past three years of a number of new approaches and more effective tools has given new hope to those engaged in the search for the underlying genetic and environmental factors involved in causing these illnesses, which collectively are among the most serious in all societies.
Abstract: ▪ Abstract There has been substantial evidence for more than three decades that the major psychiatric illnesses such as schizophrenia, bipolar disorder, autism, and alcoholism have a strong genetic basis. During the past 15 years considerable effort has been expended in trying to establish the genetic loci associated with susceptibility to these and other mental disorders using principally linkage analysis. Despite this, only a handful of specific genes have been identified, and it is now generally recognized that further advances along these lines will require the analysis of literally hundreds of affected individuals and their families. Fortunately, the emergence in the past three years of a number of new approaches and more effective tools has given new hope to those engaged in the search for the underlying genetic and environmental factors involved in causing these illnesses, which collectively are among the most serious in all societies. Chief among these new tools is the availability of the entire h...