搜索结果：Developmental neurobiology

The authors examine the biological basis for the behavioral evidence of pain perception in neonatal rats, and discuss the potential link to a greater understanding of chronic pain

CHANGING CONCEPTS IN DEVELOPMENTAL NEUROBIOLOGY* VIKTOR HAMBURGER^ I should like to take this opportunity to meditate on half a century of explorations in the field of experimental neurogenesis which I have witnessed or participated in. I shall do this in a rather personal and informal way. This, I am sure, would have the blessing of George Bishop, who had little use for formalities. To me it is still a miracle to watch the nervous system transform itself within a few weeks from a simple tube, composed of a few hundred seemingly undifferentiated embryonic cells, into the most complex organ system that has evolved in nature. So many interlocking production lines must operate with the highest precision, so many tightly programmed schedules must be met, so much could go wrong that one marvels that we all function as well as we do. But unraveling and understanding these intricacies is another matter. The neuroembryologist is overwhelmed by problems on the cellular, supercellular, and ultrastructural level. How do the literally hundreds of neuron strains, each with its own structural and biochemical identity, originate? How do they organize themselves into the supercellular units, the strata, columns, and nuclei in their precise topographic relationships? How is the circuitry established? How does an axon know on which dendritic spine to settle down? As if all this were not enough, we have to cope with the propensity of the neurons to establish intimate relations with any number of peripheral structures. This confronts us with problems of directional axon outgrowth and specific sensory and motor connections. Moreover, these relationships involve mutual dependencies of such stringency that they often decide on the life or death of the partners. By posing the problems the way I do, I reveal my bias, which is that of the experimental neuroembryologist brought up in a school where the dynamics of developmental relations and mutual interactions between *Nineteenth George H. Bishop Lecture in Experimental Neurology, given on April 19, 1974, at the Washington University School of Medicine, Saint Louis. tDepartment of Biology, Washington University, Saint Louis 63130. Research has been generously supported by the NINDS, NIH, Bethesda, Maryland. 162 I Viktor Hamburger · Developmental Neurobiology Fig. 1.—George H. Bishop (1889-1973) embryonic primordia were the primary concern. My bias was acquired in the laboratory ofH. Spemann, which in the twenties and thirties (while I was there first as a Ph.D. candidate and later as a Privatdozent) was at the zenith ofits activity. The "organizer" story was unraveling, and although I did not participate directly in this adventure, I became imbued with the spirit and the canons of experimental embryology, which in essence is the inquiry into the immediate causes or factors that determine the fate of cells and organ primordia. Today one hardly speaks of causality; we analyze mechanisms. And the term "determination," which was then the key concept, is now translated into computer language as "programPerspectives in Biology and Medicine · Winter 1975 I 163 Fig. 2.—Viktor Hamburger ming," with little net gain in basic insight. The art of microsurgery on amphibian embryos was brought to high perfection by the masters of experimental embryology, H. Spemann and R. Harrison. The aesthetic appeal added to the satisfaction of being engaged, as Spemann put it, in a direct dialogue with the living embryo, a pleasure which most modern molecular embryologists have to forgo. The focus of interest was on embryonic induction, which is a special category of developmental interactions. As it happens, the primordium of the nervous system, the neural plate, owes its existence to such an interaction, which occurs during a very early stage, the gastrulation 164 I Viktor Hamburger · Developmental Neurobiology phase. During that process, the mesoderm invaginates and its median portion applies itself closely to the overlying outer layer, the ectoderm. The mesoderm mantle then induces the formation of the neural plate in the overlying ectoderm; that is, it initiates neural differentiation by a chemical interaction. The induction was demonstrated by H. Spemann and Hilde Mangold in the classical organizer experiment on salamander embryos [1], which earned Spemann the Nobel Prize. If by appropriate transplantation a piece of mesoderm is brought into contact with a part of ectoderm that would normally...

Autism is a complex, behaviorally defined, developmental brain disorder with an estimated prevalence of 1 in 1,000. It is now clear that autism is not a disease, but a syndrome with a strong genetic component. The etiology of autism is poorly defined both at the cellular and the molecular levels. Based on the fact that seizure activity is frequently associated with autism and that abnormal evoked potentials have been observed in autistic individuals in response to tasks that require attention, several investigators have recently proposed that autism might be caused by an imbalance between excitation and inhibition in key neural systems including the cortex. Despite considerable ongoing effort toward the identification of chromosome regions affected in autism and the characterization of many potential gene candidates, only a few genes have been reproducibly shown to display specific mutations that segregate with autism, likely because of the complex polygenic nature of this syndrome. Among those, several candidate genes have been shown to control the early patterning and/or the late synaptic maturation of specific neuronal subpopulations controlling the balance between excitation and inhibition in the developing cortex and cerebellum. In the present article, we review our current understanding of the developmental mechanisms patterning the balance between excitation and inhibition in the context of the neurobiology of autism.

Hydra belongs to the class Hydrozoa in the phylum Cnidaria. Hydra is a model animal whose cellular and developmental data are the most abundant among cnidarians. Hence, I discuss the developmental neurobiology of hydra. The hydra nerve net is a mosaic of neural subsets expressing a specific neural phenotype. The developmental dynamics of the nerve cells are unique. Neurons are produced continuously by differentiation from interstitial multipotent stem cells. These neurons are continuously displaced outwards along with epithelial cells and are sloughed off at the extremities. However, the spatial distribution of each neural subset is maintained. Mechanisms related to these phenomena, i.e., the position-dependent changes in neural phenotypes, are proposed. Nerve-net formation in hydra can be examined in various experimental systems. The conditions of nerve-net formation vary among the systems, so we can clarify the control factors at the cellular level by comparing nerve-net formation in different systems. By large-scale screening of peptide signal molecules, peptide molecules related to nerve-cell differentiation have been identified. The LPW family, composed of four members sharing common N-terminal L(or I)PW, inhibits nerve-cell differentiation in hydra. In contrast, Hym355 (FPQSFLPRG-NH 3 ) activates nerve differentiation in hydra. LPWs are epitheliopeptides, whereas Hym355 is a neuropeptide. In the hypostome of hydra, a unique neuronal structure, the nerve ring, is observed. This structure shows the nerve association of neurites. Exceptionally, the tissue containing the nerve ring shows no tissue displacement during the tissue flow that involves the whole body. The neurons in the nerve ring show little turnover, although nerve cells in all other regions turn over continuously. These associations and quiet dynamics lead me to think that the nerve ring has features similar to those of the central nervous system in higher animals.

Abstract Electrophysiological kindling and behavioral sensitization to psychomotor stimulants and stress provide paradigms for understanding how repeated acute events can leave neurobiological residues in gene expression, accounting for the observed long-lasting alterations in behavioral responsivity. Kindling helps conceptualize how repeated electrical stimulation of the brain can progressively evoke increased behavioral and convulsive responsivity, leading to spontaneous seizures in the absence of exogenous stimulation following sufficient stimulations. As kindling unfolds, a complex spatiotemporal cascade of events occurs and includes the induction of immediate early genes (e.g., c-fos ) and late effector genes (including peptides and growth factors) possibly associated with the observed changes in brain microstructure (e.g., synapse formation, axonal and dendritic sprouting, apoptosis). Behavioral sensitization to psychomotor stimulants and stress has also been shown to induce related but different cascades of effects on immediate early and late effector gene expression. These may be associated with the observed long-lasting alterations in behavioral responsivity based on prior experience. If these types of alterations are put into a developmental context, this would provide a paradigm for understanding how early life events could exert profound and behaviorally relevant biochemical and microstructural effects on the central nervous system of the developing organism. The conceptual overview offered by the sensitization and kindling models suggests that environmentally triggered neurobiological processes do not form a single or static residue but, instead, engage processes related to developmental neurobiology and learning and memory and whose substrate is constantly evolving over an organism's lifetime.

I was invited to write about the discovery of Nerve Growth Factor and its relationship to developmental neurobiology. Rather than detail the life of NGF over the past 30 years, I wish to concentrate on what was the most attractive and also the most unusual feature in the investigation of NGF: that each finding has signaled a new turning point and opened up a new perspective. The story of NGF is therefore more like a detective story than a scientific enterprise, since science usually unfolds according to well-defined rules, along the route paved by previous findings. In retrospect, the previous experience with NGP holds out the promise that as many turning points still await us on the road ahead as we experienced on the road we have traveled so far. To me this is an encouraging rather than a depressing thought; the abrupt end of a scientific pursuit is more often synonymous with an intellectual dead end than with a goal successfully achieved. By way of introduction, I shall recount the early beginnings of this research, which are well known to old-timers but probably not to biochemically trained newcomers who were lured to take part in this game by the molecule itself and who are only vaguely acquainted with its natural history and with its problems.

We have determined the parameters necessary to fabricate reproducible neuronal patterns which we are using to begin studying fundamental issues in developmental neurobiology. The addition of a beam homogenizer, as well as a new surface preparation, has enabled the routine production of reproducible, high-resolution (2−20 μm) organosilane patterns. The effects of surface preparation and beam dosage were monitored using X-ray photoelectron spectroscopy (XPS) and proof of patterning is provided by high-resolution imaging XPS. We also report the guidance of neuronal adhesion and neurite outgrowth and the creation of reproducibly defined circuits of embryonic (E18−19) rat hippocampal neurons using these patterned surfaces in vitro . We have achieved a >50% rate of pattern formation, and at times the rate approaches 90%. We are using these patterns to address the issue of how geometric pattern cues might be used to affect cell-to-cell communication and we report the preliminary results on the synaptic development of the hippocampal neurons using dual patch-clamp electrophysiology. We monitored neurite outgrowth and the emergence of both spontaneous and evoked synaptic activity for both patterned and unpatterned (control) hippocampal cultures. The results indicate the intriguing possibility that geometry itself may be a modulating or trophic factor for cell development.

A fitting tribute to Viktor Hamburger, reflecting the breadth of his scientific interests and providing a critical discussion of many of the current issues in the field of developmental neurobiology.

Why are boys at risk? To address this question, I use the perspective of regulation theory to offer a model of the deeper psychoneurobiological mechanisms that underlie the vulnerability of the developing male. The central thesis of this work dictates that significant gender differences are seen between male and female social and emotional functions in the earliest stages of development, and that these result from not only differences in sex hormones and social experiences but also in rates of male and female brain maturation, specifically in the early developing right brain. I present interdisciplinary research which indicates that the stress-regulating circuits of the male brain mature more slowly than those of the female in the prenatal, perinatal, and postnatal critical periods, and that this differential structural maturation is reflected in normal gender differences in right-brain attachment functions. Due to this maturational delay, developing males also are more vulnerable over a longer period of time to stressors in the social environment (attachment trauma) and toxins in the physical environment (endocrine disruptors) that negatively impact right-brain development. In terms of differences in gender-related psychopathology, I describe the early developmental neuroendocrinological and neurobiological mechanisms that are involved in the increased vulnerability of males to autism, early onset schizophrenia, attention deficit hyperactivity disorder, and conduct disorders as well as the epigenetic mechanisms that can account for the recent widespread increase of these disorders in U.S. culture. I also offer a clinical formulation of early assessments of boys at risk, discuss the impact of early childcare on male psychopathogenesis, and end with a neurobiological model of optimal adult male socioemotional functions.

暂无摘要（点击查看原文获取完整内容）

暂无摘要（点击查看原文获取完整内容）

Editor’s Note: Two reviews in this week’s issue examine the rapidly expanding interest in autism research in the neuroscience community. Moldin et al. provide a brief prospective on the overall state of research in autism. DiCicco-Bloom and colleagues summarize their presentations at the

1 Ontogeny of the Autonomic Nervous System: Cell Line Divergence and Differentiation.- 2 Development of Peripheral Parasympathetic Neurons and Synapses.- 3 Development of the Sympathoadrenal Axis.- 4 Endocrine Control of Synaptic Development in the Sympathetic Nervous System: The Cardiac-Sympathetic Axis.- 5 Development of Ans Innervation to the Avian Heart.- 6 Development of Autonomic Innervation in Mammalian Myocardium.- 7 Autonomic Effects in the Developing Heart.- 8 Development, Aging and Plasticity of Perivascular Autonomic Nerves.- 9 Regulation of Regional Vascular Beds by the Developing Autonomic Nervous System.- 10 Relationships Between the Sympathetic Nervous System and Functional Development of Smooth Muscle End Organs.- 11 Development of Central Autonomic regulation of Cardiovascular Function.- 12 Developmental Changes in Neural Control of Respiration.- Appendix: List of Abbreviations.

How does the nervous system develop? This problem has intrigued embryologists for more than a century. In fact, early investigators formulated many of the fundamental questions about how the nervous system arises, how neurons acquire their identities, and how neuronal processes find and form synapses with appropriate target cells. To answer these questions, it would be ideal to have a single species with which cellular, molecular, and genetic analyses could be carried out on individually identified neurons and their associated cells as they develop and generate a complex nervous system. The zebrafish (Brachydunio rerio) has the potential to be such a species. In this essay, I will discuss aspects of the zebrafish that make its embryo an excellent material for developmental studies, results that have extended our knowledge of nervous system development, and future prospects for this work.

暂无摘要（点击查看原文获取完整内容）

暂无摘要（点击查看原文获取完整内容）