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Publications (846)
Neurons in the central and peripheral nervous system, including the peripheral autonomic neurons, and neurons of the diffuse gastroenteric nervous system communicate chemically at specialized junctions called synapses. The agents released by the presynaptic neurons to communicate activity to the postsynaptic neuron are called neurotransmitters.
Veterans of Operation Desert Storm/Desert Shield – the 1991 Gulf War (GW) – are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25–32% of this population suffers from a disorder characterized by symptoms that vary somewhat a...
This chapter overviews the field of neuroscience, the structure of the scientific disciplines that constitute the field, the organization of the brain, and the major areas of current research in the neurosciences at the molecular, cellular, systems, and behavioral levels of resolution. The chapter concludes with an overview of pathophysiology of br...
The fourth edition of Fundamental Neuroscience reinvents itself as an engrossing and comprehensive presentation of the discipline of neuroscience, from molecules to cognition. Thorough but succinct, and lavishly illustrated, the book builds from an introductory section that includes fundamental neuroanatomy and goes on to cover cellular and molecul...
A model is proposed in which a neurovirulent, microglial-passaged, simian immunodeficiency virus (SIV) is used to produce central nervous system (CNS) pathology and behavioral deficits in rhesus monkeys reminiscent of those seen in humans infected with human immunodeficiency virus (HIV). The time course of disease progression was characterized by u...
Throughout his long productive scientific career, Erminio Costa demonstrated several scholarly traits that illustrate a pattern for paths of successful achievement that should guide young scientists. Not only did he seek excellent training, he got and gave good mentoring. That guidance allowed him to ask important questions and to develop the metho...
Three loci that modify β-amyloid (Aβ) accumulation and deposition in the brains of a mouse model of Alzheimer's disease have been previously described. One encompasses the Psen2 gene encoding presenilin 2, a component of the γ-secretase activity responsible for generating Aβ by proteolysis. We show that the activity of mouse Psen2, as measured by l...
My goals for this perspective are to enumerate what I consider to have been the major discoveries in the investigations of the central catecholamine neuron systems from the synaptic, cellular and systems physiological and neurohistochemical perspectives. To do so, I will emphasize here the synaptic and physiological aspects of the central noradrene...
A growing problem of major proportions had been confronting biomedical scientists for many decades. Until solved, this long-neglected problem, the abject failure of the American health care system, presents a gigantic obstacle to the application of the discoveries flowing from neuropsychopharmacological research into deliverable medications utilize...
The mammalian brain varies in volume by five orders of magnitude. These size differences also affect the connectivity of the brain. In this article, we compare the cerebral and the cerebellar cortex in small and large brains. Both cortices show an almost proportionate increase in their surfaces with brain volume. However, there are fundamental diff...
Gulf War illness, the multisymptom condition resulting from service in the 1990-1991 Gulf War, is the most prominent health issue affecting Gulf War veterans, but not the only one. The Congressionally- mandated Research Advisory Committee on Gulf War Veterans' Illnesses has reviewed the extensive evidence now available, including important findings...
Despite recent scientific advances, the mechanisms inducing neuronal death in many human brain diseases remain unknown. Selective
neuronal vulnerability, often with slowly developing loss of neurons, is a common feature of neurodegenerative disorders,
infectious CNS diseases and their postinfectious states, certain forms of epilepsy, and hypoxic in...
Transgenic (Tg) mouse models of Alzheimer’s Disease (AD) provide insight into the earliest changes observable as potential
strategic targets by which to mount therapeutic interventions.Acomparison of the differentmousemodels to determine the earliest
timeatwhich diffuse or compact amyloid deposits are detected versus other structural pathology indi...
Although protein phosphorylation has been characterized more extensively, modulation of the acetylation state of signaling molecules is now being recognized as a key means of signal transduction. The enzymes responsible for mediating these changes include histone acetyl transferases and histone deacetylases (HDACs). Members of the HDAC family of en...
Central nervous system diseases constitute a major target for drug development. Genes expressed by the nervous system may represent half or more of the mammalian genome, with literally tens of thousands of gene products.
Better methods are therefore required to accelerate the pace of mapping gene expression patterns in the mouse brain and to evalua...
Nasal continuous positive airway pressure (nasal CPAP) and polysomnography were used to analyze the time course of the effect of bedtime ethanol on resistance of upper airways and on the number of respiratory pauses during sleep. On one night, six asymptomatic nonalcoholic male snorers drank 2 ml/kg of 100 proof vodka mixed in orange juice (ethanol...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which numerous mouse models have been generated. In both AD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of β-amyloid (Aβ)-containing plaques and neurodegeneration. Characterization of the timing and nature of...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which numerous mouse models have been generated. In both AD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of beta-amyloid (Abeta)-containing plaques and neurodegeneration. Characterization of the timing and nat...
The future of neurodegenerative therapeutics development depends upon effective disease modification strategies centered on carefully investigated targets. Pharmaceutical research endeavors that probe for a much deeper understanding of disease pathogenesis, and explain how adaptive or compensatory mechanisms might be engaged to delay disease onset...
The current model to explain the organization of the mammalian nervous system is based on studies of anatomy, embryology, and evolution. To further investigate the molecular organization of the adult mammalian brain, we have built a gene expression-based brain map. We measured gene expression patterns for 24 neural tissues covering the mouse centra...
Central nervous system diseases constitute a major target for drug development. Transgenic mouse models, in which genes identified in familial forms of human brain diseases are expressed in mouse neurons and glia, offer opportunities to detect and follow pathologic progression and provide potential biomarkers by which to assess therapeutic interven...
Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, beta-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (D...
To facilitate high-throughput quantitative analysis of neuronal structure, this study optimized the diOlistic method of whole neuron labeling to examine multiple neurons in fixed brain, and optimized image acquisition parameters to preserve signal for subsequent photoconversion. Fluorescent dye-coated gold particles were successively delivered by h...
Central nervous system diseases constitute a major target for drug development. Genes expressed by the nervous system may represent half or more of the mammalian genome, with literally tens of thousands of gene products. Better methods are therefore required to accelerate the pace of mapping gene expression patterns in the mouse brain and to evalua...
In situ hybridization (ISH) is an essential technique for mapping gene expression in the brain. Although many ISH protocols provide for quantitative analysis of individual mRNAs in different brain regions or across experimental conditions, this technique has lacked the necessary standardization for quantitative comparisons between different mRNA tr...
Neurons of the hypothalamo-neurohypophyseal system (HNS) are known to contain high amounts of neuronal nitric oxide (NO) synthase (nNOS). NO produced by those neurons is commonly supposed to be involved as modulator in the release of the two nonapeptides vasopressin (AVP) and oxytocin into the blood stream. Previous studies showed that forced swimm...
The role of peptides as signalling molecules in the nervous system has been studied for more than 30 years. Neuropeptides and their G-protein-coupled receptors are widely distributed throughout the body and they commonly occur with, and are complementary to, classic neurotransmitters. The functions of neuropeptides range from neurotransmitter to gr...
In this essay adapted from his Presidential Address to the AAAS annual meeting,
Floyd Bloom
makes the case that today's profound advances in biomedical research may never be effectively transformed into better health
care for society, unless steps are taken immediately to restore the American health system. He analyzes the state of the American
hea...
Various transgenic mouse models of Alzheimer's disease (AD) have been developed that overexpress mutant forms of amyloid precursor protein in an effort to elucidate more fully the potential role of beta-amyloid (A beta) in the etiopathogenesis of the disease. The present study represents the first complete 3D reconstruction of A beta in the hippoca...
High-resolution magnetic resonance microscopy (MRM) was used to determine regional brain volumetric changes in a mouse model of Alzheimer's disease. These transgenic (Tg) mice overexpress human mutant amyloid precursor protein (APP) V717F under control of platelet-derived growth factor promoter (PDAPP mice), and cortical and hippocampal beta-amyloi...
Presents an introduction to the principles of neuropharmacology, emphasizing the role and structure of proven and probable transmitters. Topics include cellular foundations of neuropharmacology, the biochemistry of the CNS, the characteristics and analysis of acetylcholine, catecholamines, serotonin, and prostaglandins, and cellular mechanisms in l...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
This classic text gives a uniquely lucid and lively view of neurotransmitters, their role in nervous system function, and their involvement in the mechanisms of psychiatric drug action. For three decades it has served as an essential guide for students of neuroscience and psychopharmacology, psychiatrists, and neurologists. Both authoritative and v...
Several signal transduction pathways have been implicated in the induction of long-term potentiation (LTP), yet the signal transduction mechanisms behind the maintenance-expression phase of LTP are still poorly understood. We investigated the role of phosphatidylinositol 3-kinase (PI3-kinase) in LTP at Schaffer collateral/commissural fiber-CA1 syna...
The study of brain development and that of behavioral development have historically proceeded independently of one another. This is an unfortunate set of circumstances, given that the disciplines concerned with development-for example, developmental psychology, pediatrics, psychiatry, clinical psychology, and the neurosciences-have much to learn fr...
Floyd Bloom says that he grew up, surrounded by doctors and pills, in a drug store in Dallas, where his father and uncles were pharmacists. He is a natural storyteller, readily recalling the people and events that have shaped his career. His narrative skills were apparent as early as high school, where he was encouraged, partially on the basis of a...
Intracellular transport and localization of cellular components are essential for the functional organization and plasticity of eukaryotic cells. Although the elucidation of protein transport mechanisms has made impressive progress in recent years, intracellular transport of RNA remains less well understood. The National Academy of Sciences Colloqu...
The World Wide Web and other forms of digital communication have led some to predict the demise of printed journals. In my experience, it is clearly demonstrable that scientific articles can be more efficiently reviewed and edited by digital document sharing. Nevertheless, high quality print journals will remain the preferred scholarly venue for au...
Members of the Src family of nonreceptor protein tyrosine kinases (PTKs) have been implicated in the regulation of cellular excitability and synaptic plasticity. We have investigated the role of these PTKs in in vitro models of epileptiform activity. Spontaneous epileptiform discharges were induced in vitro in the CA3 region of rat hippocampal slic...
A fter 5 years in the catbird seat, watching the progression of scientific discoveries move across the desks of our editors and onto our pages, it seems appropriate to reflect on the interesting times through which we have traveled together. As Editor-in-Chief, it was my good fortune to witness
W hen U.S. President Reagan signed Executive Order 12591, in April 1987, to ensure that Federal agencies and laboratories would assist universities and the private sector by moving new knowledge from the research laboratory into the development of new products and processes. The Federal Laboratory
I n a few days, it will be time to hand over the responsibilities of Editor-in-Chief of Science to Professor Don Kennedy of Stanford University. Time, as they say, flies when you are having fun, so the realization that this Editor-in-Chief has held the job for more than 5 years still seems hard to
A s a responsible editor, the views of our readers—when we can get them—offer invaluable feedback on our content's quality and accuracy as well as support for or dissent from our selections. Like all good scientists, we must also recall that skepticism is a virtue when we see readers react
E ven the most cynical spectator of the genome races will be inspired by the accomplishments presented in this special issue. Drosophila melanogaster has served biology for nearly a century, since Thomas Hunt Morgan and his students selected the fly as the subject for their studies of heredity. Not
I n the summer of 1999, then-National Institutes of Health (NIH) Director Harold Varmus's proposal to create an online electronic archive for biomedical research data sparked intense debate within the scholarly community over the best directions for the evolution of scientific publishing (see
Wiring transmission is the main form of chemical communication in the brain under most physiological conditions. However, substantial opportunity would seem to exist for the localized diffusion of transmitter, and transmitted-elicited signals, such as gases, to the releasing pre-synaptic terminal or to adjacent terminals within the immediate locale...
The World Wide Web and other forms of digital communication have lead some to predict the demise of printed journals. In my experience, scientific articles can be more efficiently reviewed and edited by digital document sharing. High quality print journals will remain the preferred scholarly venue for authors' best works, but only if the ethical be...
A ll those privileged to participate in science today should be enormously excited about the prospects for the new year and century. Scientists are now equipped with exhilaratingly powerful tools and shape their next experiments from a staggering collection of past successes. Information, let alone
In recent years, several mouse models of amyotrophic lateral sclerosis (ALS) have been developed. One, caused by a G86R mutation in the superoxide dismutase-1 (SOD-1) gene associated with familial ALS, has been subjected to extensive quantitative analyses in the spinal cord. However, the human form of ALS includes pathology elsewhere in the nervous...
In recent years, several mouse models of amyotrophic lateral sclerosis (ALS) have been developed. One, caused by a G86R mutation in the superoxide dismutase-1 (SOD-1) gene associated with familial ALS, has been subjected to extensive quantitative analyses in the spinal cord. However, the human form of ALS includes pathology elsewhere in the nervous...
This chapter discusses the multi-dimensional database requirements of brain information in the era of rapid gene identification. The chapter illustrates that even before the recent revolutions in methods to detect Expressed Sequence Tags (ESTs) of brain enriched or brain specific genes, the neurosciences had been moving rapidly, to accumulate data...
A computerized behavioral battery based upon human neuropsychological tests (CANTAB, CeNeS, Cambridge, UK) has been developed to assess cognitive behaviors of rhesus monkeys. Monkeys reliably performed multiple tasks, providing long-term assessment of changes in a number of behaviors for a given animal. The overall goal of the test battery is to ch...
O nly months apart, the editors-in-chief of the Journal of the American Medical Association ( JAMA ) and of the New England Journal of Medicine ( NEJM ) were fired. Were these two highly publicized and contentious events indicators that editorial independence is being threatened at large, society-
I t cannot have escaped readers' attention that the director of the National Institutes of Health (NIH), Harold Varmus, proposes to create an all-encompassing online electronic archive for biomedical research data, called E-biomed. In its 5 May 1999 iteration and 20 June addendum, parts of the oft-