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- Volume 22, 1999
Annual Review of Neuroscience - Volume 22, 1999
Volume 22, 1999
- Review Articles
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MONITORING SECRETORY MEMBRANE WITH FM1-43 FLUORESCENCE
Vol. 22 (1999), pp. 1–10More Less▪ AbstractFM1-43 and similar styryl dyes have proven useful as probes for membrane trafficking because they reversibly stain membranes, are impermeable to membranes, and are more fluorescent when bound to membranes than when in solution. Because these dyes stain membranes in an activity-dependent manner, they are ideal for studies of neurotransmitter release mechanisms such as synaptic vesicle recycling, exocytosis, and endocytosis. FM dyes have been used in conjunction with other techniques such as fluorescent calcium indicator dyes and electrophysiological techniques to elucidate mechanisms of presynaptic calcium homeostasis and modulation of neurotransmitter release. Presynaptic membranes have been marked by FM dyes in studies of synaptogenesis and reinnervation. As a probe for endocytosed membranes, these dyes have been used to examine vacuole formation in yeast. These versatile membrane dyes are useful in a variety of applications.
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THE CELL BIOLOGY OF THE BLOOD-BRAIN BARRIER
L. L. Rubin, and J. M. StaddonVol. 22 (1999), pp. 11–28More Less▪ AbstractThe blood-brain barrier (BBB) is formed by brain capillary endothelial cells (ECs). In the late embryonic and early postnatal period, these cells respond to inducing factors found in the brain environment by adopting a set of defined characteristics, including high-electrical-resistance tight junctions. Although the factors have not been identified definitively, a great deal of information about brain ECs has been obtained, especially recently. This review concentrates on a cell biological analysis of the BBB, with an emphasis on regulation of the specialized intercellular junctions. The development of these junctions seems to depend on two primary processes: the appearance of high levels of the tight junction protein occludin and intracellular signaling processes that control the state of phosphorylation of junctional proteins. Recent studies have revealed that the BBB can be modulated in an ongoing way to respond to environmental stimuli.
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RETINAL WAVES AND VISUAL SYSTEM DEVELOPMENT
Vol. 22 (1999), pp. 29–47More Less▪ AbstractMany pathways in the developing visual system are restructured and become highly organized even before vision occurs. Yet the developmental processes underlying the remodeling of visual connectivity are crucially dependent on retinal activity. Surprisingly, the immature and light-insensitive retina spontaneously generates a pattern of rhythmic bursting activity during the period when the connectivity patterns of retinal ganglion cells are shaped. Spatially, the activity is seen to spread across the retina in the form of waves that bring into synchrony the bursts of neighboring cells. Waves are present in the developing retina of higher and lower vertebrates, which suggests that this form of activity may be a common and fundamental mechanism employed in the activity-dependent refinement of early patterns of visual connections. Unraveling the cues encoded by the waves promises to provide important insights into how interactions driven by specific patterns of activity could lead to the modification of connectivity during development.
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MAKING BRAIN CONNECTIONS: Neuroanatomy and the Work of TPS Powell, 1923–1996
Vol. 22 (1999), pp. 49–103More Less▪ AbstractDr. Thomas PS Powell was one of the founders of modern neuroanatomy. His career spanned an era that saw techniques for analyzing connections in the central nervous system dramatically increase in number and resolving power. In tracing the history of his research, one can see how the introduction of each new technique provided an incremental step in analytical capacity although eventually revealing its own limitations. Also evident is the extent to which prejudices born in the days of applying earlier techniques could continue to influence the interpretation of results obtained with new ones. Powell's contributions to neuroscience were extremely wide-ranging, encompassing investigations of the circuitry of the basal ganglia, corticofugal connections, topographic maps in sensory systems, central olfactory pathways, corticocortical and commissural connections, and pathways for sensory convergence in the cerebral cortex. From these investigations, made with tract tracing techniques, much existing knowledge of forebrain organization is derived. He was also one of the earliest investigators to use electron microscopy in the investigation of the central nervous system, and his electron microscopic studies on the olfactory bulb, thalamus, cerebral cortex, and basal ganglia laid, to a large extent, the foundations for all modern research on the synaptic circuitry of these structures. He was given to synthesizing data across systems in order to arrive at common principles of brain organization. A number of these syntheses have been sources of great interest and, occasionally, controversy.
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STRESS AND HIPPOCAMPAL PLASTICITY
Vol. 22 (1999), pp. 105–122More Less▪ AbstractThe hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-d-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative, episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy.
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ETIOLOGY AND PATHOGENESIS OF PARKINSON'S DISEASE
C. W. Olanow, and W. G. TattonVol. 22 (1999), pp. 123–144More Less▪ AbstractParkinson's disease (PD) is an age-related neurodegenerative disorder that affects approximately 1 million persons in the United States. It is characterized by resting tremor, rigidity, bradykinesia or slowness, gait disturbance, and postural instability. Pathological features include degeneration of dopaminergic neurons in the substantia nigra pars compacta coupled with intracytoplasmic inclusions known as Lewy bodies. Neurodegeneration and Lewy bodies can also be found in the locus ceruleus, nucleus basalis, hypothalamus, cerebral cortex, cranial nerve motor nuclei, and central and peripheral components of the autonomic nervous system. Current treatment consists of a dopamine replacement strategy using primarily the dopamine precursor levodopa. While levodopa provides benefit to virtually all PD patients, after 5–10 years of treatment the majority of patients develop adverse events in the form of dyskinesia (involuntary movements) and fluctuations in motor response. Further, disease progression is associated with the development of dementia, autonomic dysfunction, and postural instability, which do not respond to levodopa therapy. Accordingly, research efforts have been directed toward understanding the etiology and pathogenesis of PD in the hope of developing a more effective therapy that will slow or halt the natural progression of PD. This paper reviews recent advances.
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COMPUTATIONAL NEUROIMAGING OF HUMAN VISUAL CORTEX
Vol. 22 (1999), pp. 145–173More Less▪ AbstractFunctional magnetic resonance imaging is a new neuroimaging method for probing the intact, alert, human brain. With this tool, brain activity that has been hidden can now be measured. Recent advances in measuring and understanding human neural responses underlying motion, color, and pattern perception are reviewed. In individual human brains, we can now identify the positions of several retinotopically organized visual areas; measure retinotopic organization within these areas; identify the location of a motion-sensitive region in individual brains; measure responses associated with contrast, color, and motion; and measure effects of attentional modulation on visually evoked responses. By framing experiments and analyses as questions about visual computation, these neuroimaging measurements can be coupled closely with those from other basic vision-science methods.
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AUTOIMMUNITY AND NEUROLOGICAL DISEASE: Antibody Modulation of Synaptic Transmission*
Vol. 22 (1999), pp. 175–195More Less▪ AbstractOver the past three decades, compelling evidence has emerged that the immune system can attack the nervous system with devastating consequences for human health. Either cell-mediated or humoral (antibody-mediated) autoimmune mechanisms may predominate in effecting a given disease, and either glia or neurons may fall under immune attack. A subset of these diseases has been particularly useful for understanding fundamental neuroscience as well as mechanisms of human disease. This subset involves humoral autoimmune attack on cell surface molecules subserving transmembrane signaling of excitable cells; special emphasis is placed here on proteins involved in synaptic transmission. We begin by reviewing the prototypic humoral autoimmune disease of synaptic transmission, myasthenia gravis. This provides a context for insights obtained from the study of diseases targeting molecules that regulate synaptic transmission at the neuromuscular junction and in the central nervous system. We also explore a disease where autoimmunity produces agonist antibodies acting at two distinct G-protein-coupled receptors. We conclude with an exploration of the vital issue of access of antibodies to targets within the central nervous system and the implications that such access may have in the pathogenesis of poorly understood idiopathic central nervous system diseases.
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MONOAMINE OXIDASE: From Genes to Behavior
J. C. Shih, K. Chen, and M. J. RiddVol. 22 (1999), pp. 197–217More Less▪ AbstractCloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B knock-out mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A. In contrast, MAO B knock-out mice do not exhibit aggression and only levels of phenylethylamine are increased. Mice lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Both MAO A and B knock-out mice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.
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MICROGLIA AS MEDIATORS OF INFLAMMATORY AND DEGENERATIVE DISEASES
Vol. 22 (1999), pp. 219–240More Less▪ AbstractMicroglia are the principal immune cells in the central nervous system (CNS) and have a critical role in host defense against invading microorganisms and neoplastic cells. However, as with immune cells in other organs, microglia may play a dual role, amplifying the effects of inflammation and mediating cellular degeneration as well as protecting the CNS. In entities like human immunodeficiency virus (HIV) infection of the nervous system, microglia are also critical to viral persistence. In this review we discuss the role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease.
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NEURAL SELECTION AND CONTROL OF VISUALLY GUIDED EYE MOVEMENTS
Vol. 22 (1999), pp. 241–259More Less▪ AbstractWe review neural correlates of perceptual and motor decisions, examining whether the time they occupy explains the duration and variability of behavioral reaction times. The location of a salient target is identified through a spatiotemporal evolution of visually evoked activation throughout the visual system. Selection of the target leads to stochastic growth of movement-related activity toward a fixed threshold to generate the gaze shift. For a given image, the neural concomitants of perceptual processing occupy a relatively constant interval so that stochastic variability in response generation introduces additional variability in reaction times.
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THE SPECIFICATION OF DORSAL CELL FATES IN THE VERTEBRATE CENTRAL NERVOUS SYSTEM
Vol. 22 (1999), pp. 261–294More Less▪ AbstractThe generation of distinct classes of neurons at defined positions within the developing vertebrate nervous system depends on inductive signals provided by local cell groups that act as organizing centers. Genetic and embryological studies have begun to elucidate the processes that control the pattern and identity of neuronal cell types. Here we discuss the cellular interactions and molecular mechanisms that direct neuronal cell fates in the dorsal half of the vertebrate central nervous system. The specification of dorsal neuronal cell fates appears to depend on a cascade of inductive signals initiated by cells of the epidermal ectoderm that flank the neural plate and propagated by roof plate cells within the neural tube. Members of the transforming growth factor−β (TGFβ) family of secreted proteins have a prominent role in mediating these dorsalizing signals. Additional signals involving members of the Wnt and fibroblast growth factor (FGF) families may also contribute to the proliferation and differentiation of dorsal neuronal cell types.
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NEUROTROPHINS AND SYNAPTIC PLASTICITY
Vol. 22 (1999), pp. 295–318More Less▪ AbstractDespite considerable evidence that neuronal activity influences the organization and function of circuits in the developing and adult brain, the molecular signals that translate activity into structural and functional changes in connections remain largely obscure. This review discusses the evidence implicating neurotrophins as molecular mediators of synaptic and morphological plasticity. Neurotrophins are attractive candidates for these roles because they and their receptors are expressed in areas of the brain that undergo plasticity, activity can regulate their levels and secretion, and they regulate both synaptic transmission and neuronal growth. Although numerous experiments show demonstrable effects of neurotrophins on synaptic plasticity, the rules and mechanisms by which they exert their effects remain intriguingly elusive.
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SPACE AND ATTENTION IN PARIETAL CORTEXfn1
Vol. 22 (1999), pp. 319–349More Less▪ AbstractThe space around us is represented not once but many times in parietal cortex. These multiple representations encode locations and objects of interest in several egocentric reference frames. Stimulus representations are transformed from the coordinates of receptor surfaces, such as the retina or the cochlea, into the coordinates of effectors, such as the eye, head, or hand. The transformation is accomplished by dynamic updating of spatial representations in conjunction with voluntary movements. This direct sensory-to-motor coordinate transformation obviates the need for a single representation of space in environmental coordinates. In addition to representing object locations in motoric coordinates, parietal neurons exhibit strong modulation by attention. Both top-down and bottom-up mechanisms of attention contribute to the enhancement of visual responses. The saliance of a stimulus is the primary factor in determining the neural response to it. Although parietal neurons represent objects in motor coordinates, visual responses are independent of the intention to perform specific motor acts.
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GROWTH CONE GUIDANCE: First Steps Towards a Deeper Understanding
Vol. 22 (1999), pp. 351–388More Less▪ AbstractGrowth cones, the hand-like structures at the tip of growing neurites, possess remarkable abilities to detect directional cues. On their way to their targets they traverse a dense jungle of many different cells, expressing a variety of different molecular guidance cues. Proper reading and integration of these cues is essential for precise wiring of different parts of the peripheral and central nervous systems. Guidance cues have been classified according to the response they elicit as either attractive or repulsive. Recent work, however, suggests that this might not represent an absolute distinction and that the internal state of the growth cone can dictate whether it detects a cue as repulsive or attractive. This article reviews some new experimental approaches to understanding growth cone signal transduction mechanisms induced by extracellular guidance cues.
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DEVELOPMENT OF THE VERTEBRATE NEUROMUSCULAR JUNCTION
Vol. 22 (1999), pp. 389–442More Less▪ AbstractWe describe the formation, maturation, elimination, maintenance, and regeneration of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses. The NMJ forms in a series of steps that involve the exchange of signals among its three cellular components—nerve terminal, muscle fiber, and Schwann cell. Although essentially any motor axon can form NMJs with any muscle fiber, an additional set of cues biases synapse formation in favor of appropriate partners. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling. NMJs regenerate following damage to nerve or muscle, but this process differs in fundamental ways from embryonic synaptogenesis. Finally, we consider the extent to which the NMJ is a suitable model for development of neuron-neuron synapses.
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PRESYNAPTIC IONOTROPIC RECEPTORS AND THE CONTROL OF TRANSMITTER RELEASE
Vol. 22 (1999), pp. 443–485More Less▪ AbstractThe quantity of neurotransmitter released into the synaptic cleft, the reliability with which it is released, and the response of the postsynaptic cell to that transmitter all contribute to the strength of a synaptic connection. The presynaptic nerve terminal is a major regulatory site for activity-dependent changes in synaptic function. Ionotropic receptors for the inhibitory amino acid GABA, expressed on the presynaptic terminals of crustacean motor axons and vertebrate sensory neurons, were the first well-defined mechanism for the heterosynaptic transmitter-mediated regulation of transmitter release. Recently, presynaptic ionotropic receptors for a large range of transmitters have been found to be widespread throughout the central and peripheral nervous systems. In this review, we first consider some general theoretical issues regarding whether and how presynaptic ionotropic receptors are important regulators of presynaptic function. We consider the criteria that should be met to identify a presynaptic ionotropic receptor and its regulatory function and review several examples of presynaptic receptors that meet at least some of those criteria. We summarize the classic studies of presynaptic inhibition mediated by GABA-gated Cl channels and then focus on presynaptic nicotinic ACh receptors and presynaptic glutamate receptors. Finally, we briefly discuss evidence for other types of presynaptic ionotropic receptors.
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MOLECULAR BIOLOGY OF ODORANT RECEPTORS IN VERTEBRATES
Vol. 22 (1999), pp. 487–509More Less▪ AbstractThe initial step in olfactory discrimination involves the interaction of odorous ligands with specific receptors on the surface of olfactory sensory neurons. The foundation for a molecular understanding of odor recognition in vertebrates was provided by the identification of a family of genes encoding putative odorant receptors, by Buck & Axel in 1991. Odorant receptor (OR) genes form the largest gene family in the vertebrate genome. This review summarizes progress over the past seven years. Major new insights are: Olfaction is accomplished in vertebrates by a very large number of receptors; olfactory sensory neurons express a small subset of the OR repertoire; in rat and mouse, axons of neurons expressing the same OR converge onto defined glomeruli in the olfactory bulb.
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CENTRAL NERVOUS SYSTEM NEURONAL MIGRATION
Vol. 22 (1999), pp. 511–539More Less▪ AbstractWidespread cell migrations are the hallmark of vertebrate brain development. In the early embryo, morphogenetic movements of precursor cells establish the rhombomeres of the hindbrain, the external germinal layer of the cerebellum, and the regional boundaries of the forebrain. In midgestation, after primary neurogenesis in compact ventricular zones has commenced, individual postmitotic cells undergo directed migrations along the glial fiber system. Radial migrations establish the neuronal layers. Three molecules have been shown to function in glial guided migration—astrotactin, glial growth factor, and erbB. In the postnatal period, a wave of secondary neurogenesis produces huge numbers of interneurons destined for the cerebellar cortex, the hippocampal formation, and the olfactory bulb. Molecular analysis of the genes that mark stages of secondary neurogenesis show similar expression patterns of a number of genes. Thus these three regions may have genetic pathways in common. Finally, we consider emerging studies on neurological mutant mice, such as reeler, and human brain malformations. Positional cloning and identification of mutated genes has led to new insights on laminar patterning in brain.
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CELLULAR AND MOLECULAR DETERMINANTS OF SYMPATHETIC NEURON DEVELOPMENT1
Vol. 22 (1999), pp. 541–566More Less▪ AbstractThe development of the sympathetic nervous system can be divided into three overlapping stages. First, the precursors of sympathetic neurons arise from undifferentiated neural crest cells that migrate ventrally, aggregate adjacent to the dorsal aorta, and ultimately differentiate into catecholaminergic neurons. Second, cell number is refined during a period of cell death when neurotrophic factors determine the number of neuronal precursors and neurons that survive. The final stage of sympathetic development is the establishment and maturation of synaptic connections, which for sympathetic neurons can include alterations in neurotransmitter phenotype. Considerable progress has been made recently in elucidating the cellular and molecular mechanisms that direct each of these developmental decisions. We review the current understanding of each of these, focusing primarily on events in the peripheral nervous system of rodents.
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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)