Showing papers in "Annual Review of Neuroscience in 1991"

Neurotransmitters in Nociceptive Modulatory Circuits

Abstract: Significant advances have been made in our understanding of nociceptive modulation from RVM. Among the most useful conceptually has been the discovery that there are two classes of modulatory neurons in the RVM that are likely to have opposing actions on nociception: on-cells, which may facilitate nociceptive transmission, and off-cells, which probably have a net inhibitory effect on nociception. The similarity in response properties among the members of each class, their large, somatic "receptive fields," and the wide distribution of the terminal fields of axons of individual neurons to the trigeminal sensory complex and to multiple spinal segments indicate that these neurons exert a global influence over nociceptive responsiveness. Drug microinjections into the RVM presumably shift the balance between states of on- or off-cell firing and also produce measurable changes in the threshold for nocifensor reflexes. The meaningful unit of function in the RVM nociceptive modulatory system therefore probably consists of large ensembles of physiologically and pharmacologically similar neurons. The strong coordination of activity of the two classes of RVM neuron may depend largely upon intranuclear projections from RVM off-cells that excite other off-cells and inhibit on-cells. The off-cell pause is GABA-mediated, and it is likely that there is a subset of GABA-containing RVM on-cells that directly inhibit off-cells. Furthermore, the available evidence indicates that exogenous opiates activate off-cells by inhibiting GABAergic release. Presumably, enkephalinergic cells in the RVM disinhibit off-cells in a similar way. Although non-serotonin-containing off-cells certainly exist, we propose that some off-cells contain serotonin. Other possible connections are based on more limited data; however, ACh, neurotensin, NE, and EAAs are present in neurons that project to the RVM, and each of these compounds, when microinjected into the RVM, has a modulating effect on nociceptive transmission. The local circuits in the RVM that underlie these actions remain to be elucidated. At the level of the dorsal horn, there is good evidence for each of three inhibitory mechanisms: direct inhibition of nociceptive projection neurons, inhibition of excitatory relay interneurons, and excitation of an inhibitory interneuron. The relative contribution made by each of these circuits is unknown.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasticity of sensory and motor maps in adult mammals.

Abstract: This rev iew addresses questions about t he capacity of sensory and motor maps in the brains of adul t mammals to change as a resul t of alterations in the effectiveness of inputs, the availability of effectors, and d irect damage. The issue of the mutabil ity of maps in adults is important because sensory and motor representations occupy much of the brains of mammals, regardless of the complexity and extent of neocortex (e.g. Kaas 1988, Wall 1988, Maunsell & Newsome 1987); behavioral recovery occurs after damage to central representations (e.g. Bor nschlegl & Asanuma 1987, Diirsteler et a11987, Eidelberg & Stein 1974); and such changes may relate to improvements in sensory and motor skills with experience (e.g. Gibson 1953). Tn addition, features of reorganization that are apparent in sensory and motor maps may characterize less easily studied areas of the brain. Specific questions addr essed in this review are as follows:

Extracellular Matrix Molecules and their Receptors: Functions in Neural Development

Abstract: The development of neurons and virtually all other cell types in the organism depends upon interactions with molecules in their environment. Studics of individual cell types have revealed tremendous diversity in the molecules that regulate the development of cells in the nervous system. These include chemotropic and trophic factors [e.g. nerve growth-factor (NGF) and brain derived neurotrophic factor (BDNF)], cell adhesion molecules [e.g. the neural cell adhesion molecule (NCAM) and N-cadherin], and molecules secreted into the extracellular matrix (ECM) [e.g. laminin (LN) and fibronectin (FN)]. Each class of molecule has now been shown to influence major steps in the development of the nervous system, including neuronal survival, determination, and migration; axonal growth and guidance; synapse formation; and glial differentiation. As molecules in the ECM influence all of these events and can be used to illustrate many of the principles derived from studies of the other classes of molecules, this review focuses upon constituents of the ECM and their receptors. The role of the ECM in neural development has recently been reviewed in this series (Sanes 1989). This review focuses on cellular and molecular themes not emphasized in the previous one and includes examples of recent work on nonneural systems that illustrate probable future directions for research in the nervous system. Recent reviews on the composition and function of the ECM and its receptors include those of Hynes (1990), Hemler (1990), Kishimoto et al (1989), Plow & Ginsberg (1989), Burgeson (1988), Buck & Horowitz (1987), McDonald (1988), Ruoslahti (1988, 1989), Fessler & Fessler (1989), and Erickson & Bourdon (1989). Reviews focusing on aspects of ECM function in neural development include those by Lander (1989), Sanes (1989), and Edgar (1989). Because of space limitations, only representative examples and references are cited in this review.

Modulation of Neural Networks for Behavior

Abstract: All animals need to shape their behavior to the demands posed by their internal and external environments. Our goal is to understand how modu­ lation of the neural networks that generate behavior occurs, so that animals can change their behavior when necessary. We discuss recent work showing that anatomical networks in the nervous system provide a physical back­ bone upon which a large library of modulatory inputs can operate. These allow the networks to produce multiple variations in output under different conditions. In the scope of this review, it is impossible to discuss all the neural circuits in which modulatory processes are now known to shape behavior (for reviews, see Selverston 1985, Harris-Warrick 1988, Kravitz 1988, Getting 1989, Bicker & Menzel 1989, Marder & Altman 1989). Instead, we have chosen examples from the literature to highlight general principles and new findings that have arisen from recent work in this field. We emphasize simple rhythmic behaviors, because more is known concerning their neural circuitry than for complex, nonrepetitive actions. As research continues, we anticipate that ideas first developed in simpler invertebrate nervous systems will be found to apply to more complex vertebrate preparations.

Mechanisms underlying long-term potentiation of synaptic transmission.

Abstract: A curious property of excitatory synapses in the hippocampus and some other neural tissues is that when they are heavily used, they undergo a long­ lasting increase in their efficacy. Brief repetitive activation of hippocampal excitatory synapses results in a substantial increase in synaptic strength that can last for several hours and has been detected even weeks after induction. This use-dependent strengthening of a synapse is known as long-term potentiation, or more commonly, LTP (Bliss & Lorna 1973, Lomo 1966, Bliss & Lynch 1988). LTP occurs most prominently in the hippocampus, where consolidation of experience into long-term memory is thought to occur. LTP is the most compelling and widely studied model

Mammalian tachykinin receptors.

Abstract: tachykinin system represents a typical ex­ ample; it comprises a group of multiple pep tides and demonstrates a func­ tional diversity at the levels of both peptide production and peptide recep­ tion. This system consists of three distinct peptides: substance P, substance K (neurokinin A), and neuromedin K (neurokinin B), all of which share the common carboxyl-termina l sequence,

Neuronal network generating locomotor behavior in lamprey: circuitry, transmitters, membrane properties, and simulation.

Abstract: All patterns of behavior are produced by interacting nerve cells. Although progress has been rapid on the level of the single nerve cell and its different types of ion channels, little or no knowledge is available on how the neural networks underlying different aspects of the vertebrate behavioral repertoire may function on a cellular level. The reason for this condition is that a detailed knowledge about the circuitry is required, for instance how different, relevant nerve cells interact, their properties, the types of synaptic interaction between interneurons, and so forth. Such detailed knowledge has been beyond reach with current techniques for these com­ plex mammalian nervous systems, which have been studied in some detail, like those of rat and cat. Nevertheless, much valuable information has been gathered about these nervous systems concerning which parts of the

Higher Order Motor Control

Abstract: (I) The anterior spinal horns and their homologues higher up (nuclei of motor cranial nerves) are the lowest motor centres (both of the cerebral and cerebellar systems). These lowest motor centres, with the corresponding sensory centres, make up the lowest level of evolution of the central nervous system. (2) The convolutions of the Rolandic region are the middle motor centres. With the corresponding sensory centres, they make up the second or middle level of the central nervous system. (3) The prae-frontal lobes are the highest motor centres of the cerebral system. With the corresponding sensory centres, thcy make up the third or highest level of the ccntral ncrvous systcm, that is, the "organ of mind. "

Mechanisms of Fast and Slow Axonal Transport

Abstract: One of the features of the neuron that most strikingly distinguishes it from other cells is its highly elongated processes. These specializations pose a particular challenge to the normal metabolic machinery of the cell. Because biosynthesis is largely restricted to the region of the cell body and the dendrites, there must be a constant flow of material from these portions of the cell out into the axon. This process is known as "anterograde" (or "orthograde") axonal transport. The return of materials toward the cell body is by "retrograde" axonal transport. Axonal transport is probably mediated by several distinct mechanisms. Evidence for multiple rate classes for anterograde transport has come from an elegant and relatively simple type of experiment. Radiolabeled amino acids are injected into the eye or into PNS ganglia to label neuronal cell bodies. Labeled proteins are then detected in the nerve as a function of time and distance, and analyzed by sodium dodecyl sulfate (SDS) poly­ acrylamide gel electrophoresis. This analysis has revealed that different proteins travel at different rates within the axon, allowing discrete classes of transported proteins to be defined. Anterograde transport alone exhibits at least five distinct rate classes

The generation of neuronal diversity in the central nervous system

Abstract: Over the course of development, proceeding from a single oocyte to an organism composed of an astounding variety of differentiated tissues, the production of the cells of the nervous system must stand as development's most ambitious feat. Not only is the system faced with the task of gen­ erating a variety of basic cell types, including both neurons and glia, but it must also produce a huge number of specific types of neurons in both the central and peripheral nervous systems-neurons that will differ in their morphologies, connections, neurotransmitters, and receptor pheno­ types. The cells that have been most closely studied in this light have been the neural crest derivatives that give rise to the PNS; these studies have yielded fascinating insights into the nature of cellular determination in the vertebrate nervous system (LeDouarin 1980, 1986, Anderson 1989). Recently, however, some exciting progress has been made in understanding the origins of cellular diversity in the central nervous system as well, and it is on this topic that this review is centered. As in the development of any tissue or cell type, neurons may make use of two basic strategies in deciding their fates. The outcome of a cell's development may be determined by its lineage-that is, by inherited pat­ terns of gene regulation or the inheritance of cytoplasmic factors that act ultimately to control gene regulation-or it may be determined by the cell's environment, broadly defined to include positional information, cell-

Molecular biology of serotonin receptors

Abstract: Serotonin (S-hydroxytryptamine; SHT) is a biogenic amine that functions as both a neurotransmitter and a hormone in the mammalian central nervous system (CNS) and in the periphery. Within the brain, serotonergic neurons originate primarily in the raphe nuclei of the brainstem and project to most areas of the CNS, where they regulate a wide variety of sensory, motor, and cortical functions (Osborne 1982). In the periphery, serotonin is involved in such diverse functions as the regulation of enteric reflexes, the modulation of platelet shape change and aggregation, the modulation of vascular smooth muscle contraction, the initiation of activity in primary afferent nociceptors, and the regulation of lymphocyte cytotoxicity and phagocytosis (for review see Peroutka 1988, Richardson & Engel 1986). Pharmacological and physiological studies have shown that the multiple actions of serotonin are mediated by several distinct cell surface receptor subtypes, designated SHTl a, Ib, lc, Id, SHT2, SHT3, and SHT4 (Bradley et aI1986). For example, the hallucinatory actions of lysergic acid diethyl­ amide (LSD) and other psychotropic serotonin analogues are probably elicited by activation of cortical 5HT2 (Rasmussen & Aghajanian 1988) or 5HTIc receptors. In contrast, the pain that is produced from applying serotonin to a blister base results from activation of 5HT3 receptors on primary sensory nerve endings (Richardson & Engel 1986). Individual serotonin receptor subtypes exhibit characteristic ligand­ binding profiles and couple to different intracellular signaling systems.

Evolution in nervous systems

Abstract: Evolution is the unifying theme of biological thought. It is therefore surprising that until recently it has little shaped the ideas of those who have sought principles among the cells and circuits of nervous systems. After relegation to an historic approach for many decades, an evolutionary perspective in neuroscience has revived, armed now with evidence available from the identified-neuron approach (Bullock & Horridge 1965; Bullock 1974; Wiersma 1974; Hoyle 1983) and fortified by modern molecular developments. In this review we have concentrated mostly on the molec­ ular, cellular, and circuit level of analysis wherever there is an evolutionary dimension, compelled for want of space to neglect the extensive fields of comparative neurology and of behavior, except for a few cases for which correlated cell or molecular information was available. Of the several good reasons for renewed interest in the evolutionary background to neural operation, two may be singled out. First, understanding how nervous systems evolve may give critical insight into otherwise inexplicable details of their construction. Animals were not designed de novo by engineers, but sculpted through natural selection acting upon variations arising within their ontogenetic programs,

Cellular and molecular biology of the presynaptic nerve terminal.

Abstract: Chemical neurotransmission represents the primary form of intercellular communication in the nervous system, yet relatively little is known about the molecular processes involved. The vesicle hypothesis states that spe­ cialized organelles located in the synaptic region are responsible for the accumulation, storage, and release of neurotransmitters in discrete packets called "quanta." These synaptic vesicles, or their components, are thought to be assembled in the cell body and transported to the terminals via fast axonal transport. At the nerve terminal, vesicles interact with the cytoskeleton and with soluble vesicle-binding proteins prior to docking at specialized membrane sites known as active zones. Following voltage­ gated Ca 2+ influx, when the local intracellular Ca 2+ concentrations ([Ca 2+]i) may reach several hundred micromolar, the vesicle and the plasma membrane fuse, releasing the vesicle contents into the synaptic cleft. A typical synaptic vesicle from a motoneuron releases approximately 5000 molecules of acetylcholine, and each nerve impulse releases 100-200 quanta at a representative neuromuscular synapse. Following exocytosis,

Genetic and Molecular Bases of Neurogenesis in Drosophila Melanogaster

Abstract: In insects, neurons in the central nervous system (CNS) are generated by progenitor cells called neuroblasts derived from a region of the ectoderm called the neurogenic region or neuroectoderm. In the neuroectoderm of Drosophila melanogaster, neighboring cells take on one of two alternative fates and develop either as neuroblasts or as epidermoblasts (progenitor cells of the epidermis). The neuroblasts move to deeper levels of the embryo to build up the central neural primordium, whereas the epidermoblasts remain at the surface to build up part of the epidermal sheath. The peri­ pheral nervous system (PNS) of insects develops from progenitor cells located within the epidermis. Thus, development of the PNS involves another choice by the epidermal cells between neural and nonneural fates, i.e. to develop as sensory progenitor cells versus non sensory epidermal cells. As is discussed in this review, many of the molecular mechanisms involved in the cell fate choices are shared in the development of the CNS and PNS. The analysis of the cellular decisions that lead to the formation of the

Structure and Function of Myelin Protein Genes

Abstract: Myelin is a unique cellular organelle produced in both the central (eNS) and peripheral (PNS) nervous systems. It plays an important role in saltatory conduction along the axon in both the eNS and PNS. eNS oligodendrocytes send out processes to recognize the axons nearby and wrap them to form compact lamellae. In the PNS, Schwann cells move around to form compact myelin lamellae. Myelination includes the process ofneuron-glia cell recognition, molecular assembly of myelin components, and compaction of membranes to form lamellar structures. The expression of several myelin proteins is highly specific to the nervous system, and, therefore, the genes coding these proteins provide good models by which to analyze gene expression in the nervous system. We focus here on the structure and function of genes encoding myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associate d glycoprotein (MAG),

THE NEURAL BASIS OF BEHAVIOR: A Neuroethological View

Abstract: The subject of this review is too broad to be covered fairly and exhaustively on so few pages, and necessary limitations in the choice of data and their interpretation reflect personal views and interests; most examples are drawn from seemingly "exotic" systems, such as electric fish, bats, and owls. A search for the neural basis of behavior requires a close integration of behavioral and neurophysiological approaches within the same system as we attempt to map phenomena of perception and motor control onto particular neuronal organizations. Studies of special model systems may yield explanations of wider applicability, and a comparison of different systems should identify general principles in neuronal design. The selection of references is not intended to be complete, to trace the history of discoveries, or to suggest priorities. Instead, these references should only assist in the search for additional sources. Therefore, more recent articles and reviews have been quoted primarily.

Molecular approaches to hereditary diseases of the nervous system: Huntington's disease as a paradigm.

Abstract: It should come as no surprise to the neurobiologist that two fifths of the 50,000-100,000 genes in the human genome are expressed in the brain. Rather more daunting is the fact that of the more than 3000 hereditary disorders described in Mendelian Inheritance in Man (McKusick 1989), one third of them produce significant CNS pathology. Only recently have we had the tools to understand these disorders on a more fundamental basis. These naturally occurring lesions of the nervous system can be exceptionally fine scalpels revealing molecules, pathways, and connections hitherto unknown. Huntington's disease (HD) has for years served as a model for teaching

Are we Willing to Fight for our Research

Abstract: In June of 1989 The Johns Hopkins Medical School celebrated its hun­ dredth anniversary. In the half-dozen speeches at the opening ceremonies, given by major figures at Hopkins, plus the Secretary of Health, the Postmaster General, and the chief executive officer of one of the country's leading pharmaceutical houses, all the important problems confront­ ing modern medicine were addressed, from AIDS to our legal system­ with one exception. Not one speaker mentioned the animal activists. After the convocation I asked my host, one of the world's leading neurophysiologists, how he could account for this. His answer: "David, they're scared to death." On February 8, 1990, the Dean of the Knoxville Tennessee School of Veterinary Medicine was murdered. He was found in the driveway of his home with eight bullets in his chest. Less than two weeks later the Boston Herald reported that animal-rights extremists had threatened to kill one veterinary-college dean each month for twelve months, as a protest against research involving the use of animals. At present these rumors remain unconfirmed, and there seems to be no shred of evidence that the murder had anything to do with the animal activists. What is significant is the immediate and instinctive reaction of those of us who use animals in our research, to have it even cross our minds that the murder might represent some new wave of fanaticism on the part of the animal-rights activists. No one who uses animals in medical research can doubt that these activists pose a most serious threat to our field and to society. I am not a scholar of the animal-activist movement and do not count myself an expert in its history or philosophy. My involvement comes partly from the fact