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- Volume 26, 2003
Annual Review of Neuroscience - Volume 26, 2003
Volume 26, 2003
- Preface
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- Review Articles
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PAIN MECHANISMS: Labeled Lines Versus Convergence in Central Processing
Vol. 26 (2003), pp. 1–30More Less▪ AbstractThe issue of whether pain is represented by specific neural elements or by patterned activity within a convergent somatosensory subsystem has been debated for over a century. The gate control theory introduced in 1965 denied central specificity, and since then most authors have endorsed convergent wide-dynamic-range neurons. Recent functional and anatomical findings provide compelling support for a new perspective that views pain in humans as a homeostatic emotion that integrates both specific labeled lines and convergent somatic activity.
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CODING OF AUDITORY SPACE
Vol. 26 (2003), pp. 31–55More Less▪ AbstractBehavioral, anatomical, and physiological approaches can be integrated in the study of sound localization in barn owls. Space representation in owls provides a useful example for discussion of place and ensemble coding. Selectivity for space is broad and ambiguous in low-order neurons. Parallel pathways for binaural cues and for different frequency bands converge on high-order space-specific neurons, which encode space more precisely. An ensemble of broadly tuned place-coding neurons may converge on a single high-order neuron to create an improved labeled line. Thus, the two coding schemes are not alternate methods. Owls can localize sounds by using either the isomorphic map of auditory space in the midbrain or forebrain neural networks in which space is not mapped.
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DECIPHERING THE GENETIC BASIS OF SPEECH AND LANGUAGE DISORDERS
Vol. 26 (2003), pp. 57–80More Less▪ AbstractA significant number of individuals have unexplained difficulties with acquiring normal speech and language, despite adequate intelligence and environmental stimulation. Although developmental disorders of speech and language are heritable, the genetic basis is likely to involve several, possibly many, different risk factors. Investigations of a unique three-generation family showing monogenic inheritance of speech and language deficits led to the isolation of the first such gene on chromosome 7, which encodes a transcription factor known as FOXP2. Disruption of this gene causes a rare severe speech and language disorder but does not appear to be involved in more common forms of language impairment. Recent genome-wide scans have identified at least four chromosomal regions that may harbor genes influencing the latter, on chromosomes 2, 13, 16, and 19. The molecular genetic approach has potential for dissecting neurological pathways underlying speech and language disorders, but such investigations are only just beginning.
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EPIDEMIOLOGY OF NEURODEGENERATION
Vol. 26 (2003), pp. 81–104More Less▪ AbstractAlzheimer's disease, Parkinson's disease, and motor neuron disease share a propensity to occur with increasing age and as either a sporadic or a familial disorder. A number of behavioral and environmental risk factors have been proposed for each disorder, but most associations lack consistency and specificity. Over the last decade the remarkable frequency of these disorders has become apparent, and the identification of mutations in genes has provided the means to understand their pathogenesis. Better and more accurate means to characterize and diagnose these diseases has greatly facilitated analytic epidemiology. The analysis of behavioral and genetic factors that may lower disease risk has led to clinical trials that are either in progress or being planned with the aim of preventing these disorders.
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NOVEL NEURAL MODULATORS
Vol. 26 (2003), pp. 105–131More Less▪ AbstractThe discovery that nitric oxide (NO) is produced by neurons and regulates synaptic activity has challenged the definition of a neurotransmitter. NO is not stored in synaptic vesicles and does not act at conventional receptors on the surface of adjacent neurons. The toxic gases carbon monoxide (CO) and hydrogen sulfide (H2S) are also produced by neurons and modulate synaptic activity. D-serine synthesis and release by astrocytes as an endogenous ligand for the “glycine” site of N-methyl D-aspartate (NMDA) receptors defy the concept that a neurotransmitter must be synthesized by neurons. We review the properties of these “atypical” neural modulators.
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THE NEUROBIOLOGY OF VISUAL-SACCADIC DECISION MAKING
Vol. 26 (2003), pp. 133–179More Less▪ AbstractOver the past two decades significant progress has been made toward understanding the neural basis of primate decision making, the biological process that combines sensory data with stored information to select and execute behavioral responses. The most striking progress in this area has been made in studies of visual-saccadic decision making, a system that is becoming a model for understanding decision making in general. In this system, theoretical models of efficient decision making developed in the social sciences are beginning to be used to describe the computations the brain must perform when it connects sensation and action. Guided in part by these economic models, neurophysiologists have been able to describe neuronal activity recorded from the brains of awake-behaving primates during actual decision making. These recent studies have examined the neural basis of decisions, ranging from those made in predictable sensorimotor tasks to those unpredictable decisions made when animals are engaged in strategic conflict. All of these experiments seem to describe a surprisingly well-integrated set of physiological mechanisms that can account for a broad range of behavioral phenomena. This review presents many of these recent studies within the emerging neuroeconomic framework for understanding primate decision making.
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COLOR VISION
Vol. 26 (2003), pp. 181–206More Less▪ AbstractColor vision starts with the absorption of light in the retinal cone photoreceptors, which transduce electromagnetic energy into electrical voltages. These voltages are transformed into action potentials by a complicated network of cells in the retina. The information is sent to the visual cortex via the lateral geniculate nucleus (LGN) in three separate color-opponent channels that have been characterized psychophysically, physiologically, and computationally. The properties of cells in the retina and LGN account for a surprisingly large body of psychophysical literature. This suggests that several fundamental computations involved in color perception occur at early levels of processing. In the cortex, information from the three retino-geniculate channels is combined to enable perception of a large variety of different hues. Furthermore, recent evidence suggests that color analysis and coding cannot be separated from the analysis and coding of other visual attributes such as form and motion. Though there are some brain areas that are more sensitive to color than others, color vision emerges through the combined activity of neurons in many different areas.
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NEW INSIGHTS INTO THE DIVERSITY AND FUNCTION OF NEURONAL IMMUNOGLOBULIN SUPERFAMILY MOLECULES
Vol. 26 (2003), pp. 207–238More Less▪ AbstractImmunoglobulin superfamily (IgSF) proteins are implicated in diverse steps of brain development, including neuronal migration, axon pathfinding, target recognition and synapse formation, as well as in the maintenance and function of neuronal networks in the adult. We provide here a review of recent findings on the diversity and the role of transmembrane and secreted members of IgSF proteins in the nervous system. We illustrate that the complexity of IgSF protein function results from various different levels of regulation including regulation of gene expression, protein localization, and protein interactions.
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BREATHING: Rhythmicity, Plasticity, Chemosensitivity
Vol. 26 (2003), pp. 239–266More Less▪ AbstractBreathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBötzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.
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PROTOFIBRILS, PORES, FIBRILS, AND NEURODEGENERATION: Separating the Responsible Protein Aggregates from The Innocent Bystanders*
Vol. 26 (2003), pp. 267–298More Less▪ AbstractMany neurodegenerative diseases, including Alzheimer's and Parkinson's and the transmissible spongiform encephalopathies (prion diseases), are characterized at autopsy by neuronal loss and protein aggregates that are typically fibrillar. A convergence of evidence strongly suggests that protein aggregation is neurotoxic and not a product of cell death. However, the identity of the neurotoxic aggregate and the mechanism by which it disables and eventually kills a neuron are unknown. Both biophysical studies aimed at elucidating the precise mechanism of in vitro aggregation and animal modeling studies support the emerging notion that an ordered prefibrillar oligomer, or protofibril, may be responsible for cell death and that the fibrillar form that is typically observed at autopsy may actually be neuroprotective. A subpopulation of protofibrils may function as pathogenic amyloid pores. An analogous mechanism may explain the neurotoxicity of the prion protein; recent data demonstrates that the disease-associated, infectious form of the prion protein differs from the neurotoxic species. This review focuses on recent experimental studies aimed at identification and characterization of the neurotoxic protein aggregates.
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SELECTIVITY IN NEUROTROPHIN SIGNALING: Theme and Variations
Vol. 26 (2003), pp. 299–330More Less▪ AbstractNeurotrophins are a family of growth factors critical for the development and functioning of the nervous system. Although originally identified as neuronal survival factors, neurotrophins elicit many biological effects, ranging from proliferation to synaptic modulation to axonal pathfinding. Recent data indicate that the nature of the signaling cascades activated by neurotrophins, and the biological responses that ensue, are specified not only by the ligand itself but also by the temporal pattern and spatial location of stimulation. Studies on neurotrophin signaling have revealed variations in the Ras/MAP kinase, PI3 kinase, and phospholipase C pathways, which transmit spatial and temporal information. The anatomy of neurons makes them particularly appropriate for studying how the location and tempo of stimulation determine the signal cascades that are activated by receptor tyrosine kinases such as the Trk receptors. These signaling variations may represent a general mechanism eliciting specificity in growth factor responses.
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BRAIN REPRESENTATION OF OBJECT-CENTERED SPACE IN MONKEYS AND HUMANS
Vol. 26 (2003), pp. 331–354More Less▪ AbstractVisuospatial cognition requires taking into account where things are relative to each other and not just relative to the viewer. Consequently it would make sense for the brain to form an explicit representation of object-centered and not just of ego-centered space. Evidence bearing on the presence and nature of neural maps of object-centered space has come from two sources: single-neuron recording in behaving monkeys and assessment of the visual abilities of human patients with hemispatial neglect. Studies of the supplementary eye field of the monkey have revealed that it contains neurons with object-centered spatial selectivity. These neurons fire when the monkey has selected, as target for an eye movement or attention, a particular location defined relative to a reference object. Studies of neglect have revealed that in some patients the condition is expressed with respect to an object-centered and object-aligned reference frame. These patients neglect one side of an object, as defined relative to its intrinsic midline, regardless of its location and orientation relative to the viewer. The two sets of observations are complementary in the sense that the loss of neurons, such as observed in the monkey, could explain the spatial distribution of neglect in these patients.
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GENERATING THE CEREBRAL CORTICAL AREA MAP
Vol. 26 (2003), pp. 355–380More Less▪ AbstractThe view that the cortical primordium is initially patterned in similar ways to the rest of the embryo has been a conceptual breakthrough. We now have a new starting point for understanding how the cortical area map is established and how maps may change and evolve. Here we review findings that signaling molecules secreted from distinct cortical signaling centers establish positional information in the cortical primordium and regulate regional growth. In other embryonic systems, positional signals would regulate the patterned expression of transcription factors, leading, in a gene regulatory cascade, to the patterned differentiation of the tissue. We discuss candidate transcription factors with respect to such a model of cortical patterning. Finally, embryonic structures interact to pattern one another. We review data suggesting that the thalamus and cortex are patterned independently then interact to generate the final cortical area map.
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INFERENCE AND COMPUTATION WITH POPULATION CODES
Vol. 26 (2003), pp. 381–410More Less▪ AbstractIn the vertebrate nervous system, sensory stimuli are typically encoded through the concerted activity of large populations of neurons. Classically, these patterns of activity have been treated as encoding the value of the stimulus (e.g., the orientation of a contour), and computation has been formalized in terms of function approximation. More recently, there have been several suggestions that neural computation is akin to a Bayesian inference process, with population activity patterns representing uncertainty about stimuli in the form of probability distributions (e.g., the probability density function over the orientation of a contour). This paper reviews both approaches, with a particular emphasis on the latter, which we see as a very promising framework for future modeling and experimental work.
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MOLECULAR APPROACHES TO SPINAL CORD REPAIR
Vol. 26 (2003), pp. 411–440More Less▪ AbstractAxon growth inhibitors associated with myelin and the glial scar contribute to the failure of axon regeneration in the injured adult mammalian central nervous system (CNS). A number of these inhibitors, their receptors, and signaling pathways have been identified. These inhibitors can now be neutralized by a variety of approaches that point to the possibility of developing new therapeutic strategies to stimulate regeneration after spinal cord injury.
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CELL MIGRATION IN THE FOREBRAIN
Vol. 26 (2003), pp. 441–483More Less▪ AbstractThe forebrain comprises an intricate set of structures that are required for some of the most complex and evolved functions of the mammalian brain. As a reflection of its complexity, cell migration in the forebrain is extremely elaborated, with widespread dispersion of cells across multiple functionally distinct areas. Two general modes of migration are distinguished in the forebrain: radial migration, which establishes the general cytoarchitectonical framework of the different forebrain subdivisions; and tangential migration, which increases the cellular complexity of forebrain circuits by allowing the dispersion of multiple neuronal types. Here, we review the cellular and molecular mechanisms underlying each of these types of migrations and discuss how emerging concepts in neuronal migration are reshaping our understanding of forebrain development in normal and pathological situations.
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CELL-CELL SIGNALING DURING SYNAPSE FORMATION IN THE CNS
Vol. 26 (2003), pp. 485–508More Less▪ AbstractSynapses join individual nerve cells into a functional network. Specific cell-cell signaling events regulate synapse formation during development and thereby generate a highly reproducible connectivity pattern. The accuracy of this process is fundamental for normal brain function, and aberrant connectivity leads to nervous system disorders. However, despite the overall precision with which neuronal circuits are formed, individual synapses and synaptic networks are also plastic and can readily adapt to external stimuli or perturbations. In recent studies, several trans-synaptic signaling systems have been identified that can mediate various aspects of synaptic differentiation in the central nervous system. It appears that these individual pathways functionally cooperate, thereby generating robustness and flexibility, which ensure normal nervous system function.
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SIGNALING AT THE GROWTH CONE: Ligand-Receptor Complexes and the Control of Axon Growth and Guidance
Vol. 26 (2003), pp. 509–563More Less▪ AbstractThe guidance of axons during the establishment of the nervous system is mediated by a variety of extracellular cues that govern cytoskeletal dynamics in axonal growth cones. A large number of these guidance cues and their cell-surface receptors have now been identified, and the intracellular signaling pathways by which these cues induce cytoskeletal rearrangements are becoming defined. This review summarizes our current understanding of the major families of axon guidance cues and their receptors, with a particular emphasis on receptor signaling mechanisms. We also discuss recent advances in understanding receptor cross talk and how the activities of guidance cues and their receptors are modulated during neural development.
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NOTCH AND PRESENILIN: Regulated Intramembrane Proteolysis Links Development and Degeneration
Vol. 26 (2003), pp. 565–597More Less▪ AbstractIntensive studies of three proteins—Presenilin, Notch, and the amyloid precursor protein (APP)—have led to the recognition of a direct intersection between early development and late-life neurodegeneration. Notch signaling mediates many different intercellular communication events that are essential for determining the fates of neural and nonneural cells during development and in the adult. The Notch receptor acts in a core pathway as a membrane-bound transcription factor that is released to the nucleus by a two-step cleavage mechanism called regulated intramembrane proteolysis (RIP). The second cleavage is effected by Presenilin, an unusual polytopic aspartyl protease that apparently cleaves Notch and numerous other single-transmembrane substrates within the lipid bilayer. Another Presenilin substrate, APP, releases the amyloid ß-protein that can accumulate over time in limbic and association cortices and help initiate Alzheimer's disease. Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease.
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Previous Volumes
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Volume 47 (2024)
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Volume 46 (2023)
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Volume 45 (2022)
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Volume 44 (2021)
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Volume 43 (2020)
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Volume 42 (2019)
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Volume 41 (2018)
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Volume 40 (2017)
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Volume 39 (2016)
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Volume 38 (2015)
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Volume 37 (2014)
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Volume 36 (2013)
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Volume 35 (2012)
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Volume 34 (2011)
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Volume 33 (2010)
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Volume 32 (2009)
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Volume 31 (2008)
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Volume 30 (2007)
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Volume 29 (2006)
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Volume 28 (2005)
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Volume 27 (2004)
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Volume 26 (2003)
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Volume 25 (2002)
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Volume 24 (2001)
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Volume 23 (2000)
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Volume 22 (1999)
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Volume 21 (1998)
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Volume 20 (1997)
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Volume 19 (1996)
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Volume 18 (1995)
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Volume 17 (1994)
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Volume 16 (1993)
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Volume 15 (1992)
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Volume 14 (1991)
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Volume 13 (1990)
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Volume 12 (1989)
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Volume 11 (1988)
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Volume 10 (1987)
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Volume 9 (1986)
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Volume 8 (1985)
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Volume 7 (1984)
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Volume 6 (1983)
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Volume 5 (1982)
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Volume 4 (1981)
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Volume 3 (1980)
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Volume 2 (1979)
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Volume 1 (1978)
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Volume 0 (1932)