Showing papers in "Annual Review of Neuroscience in 1983"

Spinal and Trigeminal Mechanisms of Nociception

Abstract: The development of new experimental approaches has led to recent ad­ vances in our knowledge of spinal and trigeminal nociceptive mechanisms, justifying another review of the rapidly proliferating literature in this field. We examine neural circuits and sensory mechanisms activated by noxious or painful stimulation of undamaged skin and peripheral nerves. The spinal dorsal horn and its homolog in the trigeminal system consist of three major components:

The Classification of Dopamine Receptors: Relationship to Radioligand Binding

Abstract: The past 25 years has seen our appreciation of the function of dopamine (DA) in the brain elevated from that of a precursor for norepinephrine to a neurotransmitter in its own right. The association of disturbances of dopaminergic neurotransmission with neurological and psychiatric disor­ ders has further emphasized the crucial role of this neurotransmitter in normal brain function. Dopaminergic agonists have a firmly established role in the treatment of Parkinson's disease and may be of value in the therapy of tardive dyskinesia. Dopaminergic antagonists have a longer history in the treatment of schizophrenia, Huntington's disease, and Gilles de la Touret­ te's syndrome. Since 1975, the elegantly simple radioligand binding technique has al­ lowed direct examination of the interactions of agonists and antagonists with putative dopamine receptors (DARs), and these studies form the major focus of this review. Such studies have complemented investigations ofDA regulation of adenylate cyclase activity and hormone release in various tissues. Although problems remain, the correspondence between such radi­ oligand binding sites and functional DARs is steadily being established. These experiments have clearly divided DARs into distinct subtypes, much as was done earlier for the alpha and beta adrenergic receptors. These findings will have a profound effect on our understanding of dopaminergic

Microcircuitry of the cat retina.

Abstract: As a device for extracting information from a visual image, the vertebrate retina is unparalleled in its range, reliability, and compactness. Signaling in the retina is slower by six orders of magnitude than in an integrated digital circuit. The advantage of the biological structure must therefore derive from the variety of its fundamental elements and from the subtlety of their connections. Each of the five major classes of retinal neuron, whose synaptic contacts were first described systematically by Dowling & Boycott (1966), is now known to have multiple types, totaling in the cat about 60. Specific local circuits involving about one-third of these neurons have been recog­ nized in the electron microscope. Physiological responses have also been documented for about one-third of the types, and evidence regarding the neural transmitter, or at least the sign of the synapse, has accumulated also for about one-third. These discoveries have abundantly supported certain concepts of retinal function developed in the 1960s by Lettvin & Maturana. The function of the retina, they proposed, "is not to transmit information about the point­ to-point distribution of light and dark in the image, but to analyze this image at every point in terms of ... arbitrary contexts ... " (Maturana et at 1960). Each of'these "contexts," they suggested, corresponds to some operation on the local image performed by a ganglion cell of particular size and shape (Lettvin et al 1961). This idea, based on studies of the frog, seemed for a time inapplicable to the cat, which was thought to have a "simple" retina with only center-surround type ganglion cells. Subsequent studies to be reviewed here have firmly established for the cat the validity of this idea.

Mechanoelectrical transduction by hair cells in the acousticolateralis sensory system.

Abstract: Hair cells are sensory receptors that occur ubiquitously in the vertebrate sensory organs, collectively constituting the acousticolateralis system, re­ sponsible for the detection of sound, linear and angular accelerations, water motion, and substrate vibration. In subserving these various sensitivities, hair cells occur in organs of widely di1fering structures and of frequency sensitivities covering the range 0-100 kHz. Despite this variability of envi­ ronment and function, however, all hair cells share a sensory apparatus of similar structure and all seem to operate in fundamentally the same manner. This paper describes the structure of the sensory apparatus of hair cells and what is known of their transduction process. In the context of the acousticolateralis system, the term "transduction" is employed with both a broad and a narrow meaning. In the general sense, transduction is taken to include the whole complex of events-acoustical, mechanical, hydrodynamic, and physiological-that occur between the ap­ plication of stimuli and genesis of a neural response. The present review focuses on transduction in its more restricted, cellular sense, as the transfor­ mation of a mechanical stimulus into a conductance change and an elec­ trical response of the hair cell's membrane. Because the number of publications addressing this point is fairly restricted, and since there have

Cellular Processes of Learning and Memory in the Mammalian CNS

Abstract: A number of reviews on various aspects of the neuronal bases of learning and memory have appeared in the past few years (Agranoff et al 1978, Bennett 1976, Dunn 1980, Greenough 1976, Kandel & Spencer 1968, Kup­ fermann 1975, McGaugh & Herz 1972, Rosenzweig & Bennett 1976, Soko­ lov 1977, Squire 1982, Squire & Davis 1981, Thompson et alI972, 1980, Tsukahara 1981). This review is concerned broadly with the cellular/neu­ ronal processes of associative learning in the mammalian brain.! The nature of the memory trace has proved to be among the most baffiing questions in science. The problem of localization has been perhaps the greatest barrier. In order to characterize cellular mechanisms of information storage and

Positron emission tomography.

Abstract: An understanding of disease processes in the human brain must ultimately be based on a knowledge of the underlying regional hemodynamic, metabolic, and biochemical changes. Although some such information is currently available from various animal models, the conflicting nature of these data often leaves many important questions unanswered and emphasizes the immense difficulty of developing and studying laboratory models of human disease. One obvious alternative is to develop a means by which the hemodynamic, biochemical and metabolic bases of cerebral disease can be safely studied sequentially in humans by using externally detected radiolabeled tracers.

Experimental approaches to understanding the role of protein phosphorylation in the regulation of neuronal function

Abstract: Studies by Earl Sutherland and his colleagues on hormonal regulation of the breakdown of glycogen in liver resulted in the discovery that the first step in the action of many hormones is to increase the synthesis of cAMP by activating adenylate cyclase (Raft et al 1957, Sutherland & Rall 1958, Robison et al 1968). It was later established that cAMP exerts its effects by stimulating protein kinases that catalyze the phosphorylation of specific functional proteins and thereby regulate their activity (Walsh et al 1968, Kuo & Greengard 1969, Krebs & Beavo 1979). The discovery that the brain contains a high concentration of cAMP-dependent protein kinase led to the proposal that protein phosphorylation might play an important role in regulation of neuronal properties by neurotransmitters and neurohormones (Miyamoto et al 1969). In particular, it seemed that protein phosphorylation, which usually takes place on a time scale of hundreds of milliseconds or longer, might be a mechanism underlying relatively long-lasting changes in neuronal properties such as "slow" changes in post-synaptic potentials (McAfee & Greengard 1972), changes in the rate of transmitter synthesis (Morgenroth et al 1975), or changes in gene expression (Klein & Berg 1970). The biochemists and neurobiologists who took up the study of brain protein phosphorylation hoped to gain insight into some of the mechanisms underlying changes in neuronal excitability and synaptic efficacy and also, perhaps, into processes that govern the development of various neuronal types during the formation of the nervous system. This line of research was bolstered by the findings that the brain contains not only high concentrations of protein kinases, but also protein phosphatases, adenylate cyclase, and phosphodiesterase (Greengard 1976), and also by the discovery that several neurotransmitters stimulate the synthesis of second messengers such as cyclic AMP and cyclic GMP by binding to specific receptors on the surfaces of neurons (for reviews see Nathanson 1977, Greengard 1981).

Isolation and Reconstitution of Neuronal ION Transport Proteins

Abstract: Introduction The electrical activity of nerve cells is produced by the coordinated gating and pumping of ions across the neuronal membrane. It is axiomatic that regulation of neuronal electrical activity is due to regulation of these ion transport proteins. Examples of primary regulatory mechanisms are (0) the depolarization of the nerve cell membrane that induces the opening of the voltage-sensitive action potential Na+ channel and (b) the conductance change directly induced by the binding of neurotransmitters to postsynaptic receptor sites. More indirect and in some cases simultaneous secondary mechanisms of regulation are postulated to occur, e.g. via phosphorylation of ion transport proteins resulting from a cyclic nucleotide-mediated series of events (reviewed by Kennedy 1983). Identifying these neuronal ion transport proteins and reconstituting them in a purified, biologically active form can help answer a variety of questions. The mechanisms of gene replication (DePampbilis & Wassarman 1980) and muscle contraction (Adelstein & Eisenberg 1980) are studied by isolating the enzymes and other components involved and determining how they function and interact with each other in vitro. Studying the mechanism and regulation of purified, reconstituted ion transport proteins could provide similar information about the molecular basis of neuronal electrical activity. If one can then proceed immunocytochemically to localize specific classes of these transport proteins in the eNS (together with using information provided by neuroanatomical techniques), one could in principle obtain a functional map of their distribution in neuronal pathways that might help

Nobel Laureates in Neuroscience: 1904-1981

Abstract: Prompted by the award of the Nobel Prize in Physiology or Medicine to three of our most distinguished neuroscientists in 1981, David Hubel, Tors­ ten Wiesel, and Roger Sperry, it would seem an appropriate time to present a brief review of Nobel Laureates in Neuroscience over the years. This provides an interesting thumbnail sketch of some of the highlights in the historical development of neuroscience since the turn of the century.1 The field of neuroscience has become so broad during recent years as to involve aspects of most biological and many medical sciences, as well as many discoveries in physics and chemistry. We confine our selection to the Prizes in Physiology or Medicine for discoveries directly related to the nervous system. This account is further condensed by the format of this Prefatory Chapter, but we try to overcome this limitation to some extent by giving references to some of the principal publications of each of the Prize winners in the bibliography. We present our own evaluations and

Molecular Approaches to the Nervous System

Abstract: Hybridoma and recombinant DNA technologies promise a major advance in our understanding of the molecular basis of the function of the nervous system. The issues we hope to approach with these new tools include (a) the molecular determinants of membrane permeability, (b) cellular heterogeneity of the nervous system, and (c) the epigenetic events of neural development. Because the application of these new approaches is only recent, it is not possible at this stage to predict full answers, but only to describe the strategies that promise to be success ful. This review is an introduction to the early applications of these technologies to neuroscience and is deliberately selective, emphasizing a few specific problems in the hope that these strategies may be generally applicable to many areas of interest in neurobiology.