The Coordination And Role Of Activity In Developing Neural Circuits

The stereotyped synaptic connections that define neural circuit function are established during development. Neuronal activity independent of environmental stimulus contributes to neural circuit assembly in vertebrates, but its precise role remains an open question, particularly at the level of defined cell types. By contrast, invertebrate neurodevelopment was thought to proceed in the absence of such developmental activity. Here I show that developmental activity accompanies synaptogenesis in the Drosophila brain. Using Drosophila genetics, epifluorescence microscopy, two-photon microscopy, immunohistochemistry, and visual behavior, I characterize this developmental activity, determine its role in synapse formation, and identify regulatory mechanisms at the cellular and molecular level. This patterned-stimulus independent neural activity occurs in a brain-wide fashion, and is characterized by stereotyped oscillations and cellular dynamics that reflect synaptic connectivity. Activity patterns instruct synapse development in a cell-type-specific manner. A transient and genetically specified population of neurons propagates this activity throughout the brain. Glia participate with complementary cycles of activity in a cell-type-specific fashion, and astrocytes are necessary for activity to occur. These data indicate that developmental activity is an evolutionarily conserved and fundamental component of neural circuit assembly that is coordinated by multiple molecular and cellular mechanisms.

Development of the Visual System presents a selection of current studies that clearly illustrate principles of visual system development. These range from retinal development in fish and frogs to the effects of abnormal visual experience on the primary visual cortex of the cat. The book is unique in addressing four specific and fundamental aspects of development: cell lineage and cell fate, specificity and targeting of axons, specification of visual cortex, and correlates of the critical period. Encompassing technical advances in cellular and molecular biology and in video imaging and microscopy, contributions in each of these areas provide new information at the cellular and molecular levels to complement the now classic descriptions of visual development previously available at the level of neural systems.ContributorsKaren L. Allendoerfer, David M. Altshuler, Antonella Antonini, Seymour Benzer, Edward M. Callaway, Constance L. Cepko, Hollis T. Cline, Max S. Cynader, N. W. Daw, Scott E. Fraser, K. Fox, Eckhard Friauf, Anirvan Ghosh, R. W. Guillery, William A. Harris, Christine E. Holt, Lawrence C. Katz, Susan McConnell, Pamela A. Raymond, Thomas A. Reh, Carla J. Shatz, Michael P. Stryker, Claudia A. 0. Stuermer, Mriganka Sur, David L. Turner, T. N. Wiesel

How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media. How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a working family, the effect of politics on programs for children, the costs and benefits of intervention, and other issues. The committee issues a series of challenges to decision makers regarding the quality of child care, issues of racial and ethnic diversity, the integration of children's cognitive and emotional development, and more. Authoritative yet accessible, From Neurons to Neighborhoods presents the evidence about "brain wiring" and how kids learn to speak, think, and regulate their behavior. It examines the effect of the climate-family, child care, community-within which the child grows.

Neural Circuit and Cognitive Development, Second Edition, the latest release in the Comprehensive Developmental Neuroscience series, provides a much-needed update to underscore the latest research in this rapidly evolving field, with new section editors discussing the technological advances that are enabling the pursuit of new research on brain development. This volume is devoted mainly to anatomical and functional development of neural circuits and neural systems and cognitive development. Understanding the critical role these changes play in neurodevelopment provides the ability to explore and elucidate the underlying causes of neurodevelopmental disorders and their effect on cognition. This series is designed to fill the knowledge gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Features leading experts in various subfields as section editors and article authors Presents articles that have been peer reviewed to ensure accuracy, thoroughness and scholarship Includes coverage of mechanisms that control the assembly of neural circuits in specific regions of the nervous system and multiple aspects of cognitive development

The genetic, molecular, and cellular mechanisms of neural development are essential for understanding evolution and disorders of neural systems. Recent advances in genetic, molecular, and cell biological methods have generated a massive increase in new information, but there is a paucity of comprehensive and up-to-date syntheses, references, and historical perspectives on this important subject. The Comprehensive Developmental Neuroscience series is designed to fill this gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Particular attention is paid to the effects of abnormal development and on new psychiatric/neurological treatments being developed based on our increased understanding of developmental mechanisms. Each volume in the series consists of review style articles that average 15-20pp and feature numerous illustrations and full references. Volume 3 offers 40 high level articles devoted mainly to anatomical and functional development of neural circuits and neural systems, as well as those that address neurodevelopmental disorders in humans and experimental organisms. Series offers 144 articles for 2904 full color pages addressing ways in which the nervous system and its components develop Features leading experts in various subfields as Section Editors and article Authors All articles peer reviewed by Section Editors to ensure accuracy, thoroughness, and scholarship Volume 3 sections include coverage of: mechanisms that control the assembly of neural circuits in specific regions of the nervous system, multiple aspects of cognitive development, and disorders of the nervous system arising through defects in neural development

Intercellular communication is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their environment is the basis of growth and development, tissue repair, and immunity as well as normal tissue homeostasis. Errors in cellular information processing are responsible for diseases such as cancer, autoimmunity, diabetes, and neurological and psychiatric disorders. There is substantial drug development concentrating on this and intercellular communication is the basis of much of neuropharmacology. By understanding cell signaling, diseases may be treated effectively and, theoretically, artificial tissues may be yielded. Neurotransmitters/receptors, synaptic structure and organization, gap junctions, neurotrophic factors and neuropeptides are all explored in this volume, as are the ways in which signaling controls neuroendocrinology, neuroimmunology and neuropharmacology. Intercellular Communication in the Nervous System provides a valuable desk reference for all scientists who consider signaling. Chapters offer impressive scope with topics addressing neurotransmitters/receptors, synaptic structure and organization, neuropeptides, gap junctions, neuropharmacology and more Richly illustrated in full color with over 200 figures Contributors represent the most outstanding scholarship in the field, with each chapter providing fully vetted and reliable expert knowledge

"At the onset of early postnatal development, neural circuits are initially imprecise; axons innervate an excessive number of targets, and target neurons receive inputs from a surplus of converging axons, resulting in diffuse circuits with overlapping connections. As activity increases over time, these circuits improve their performance by refining their connections, strengthening some and eliminating others. Moreover, if there is no activity in the circuit, then the refinement of connections does not occur. It is generally thought that the increase in synaptic transmission drives refinement by stimulating the postsynaptic neuron to release retrograde signals that act locally on presynaptic inputs. However, abolishing synaptic transmission at one node of a circuit alters synaptic activity in downstream target neurons and organs. Often overlooked is the possibility that activity-dependent, target-derived factors play an essential role in mediating the refinement of connections on upstream neurons. Such long-range factors would coordinate refinement of upstream connections in a retrograde manner to establish circuits that innervate distal targets with specificity and precision. The main objective of my doctoral research was to improve our understanding of the mechanisms that underlie refinement by (i) investigating how neural circuits develop in the absence of postsynaptic activity; (ii) determining whether downstream target organs have a role in the retrograde regulation of neural development; and (iii) identifying molecular mechanisms involved in refinement.To address these issues, I compared the development of sympathetic circuits in three mouse models. In one model, mice have a deletion in the [alpha]3 nAChR subunit gene ([alpha]3 KO), an essential gene for the assembly of postsynaptic receptors on autonomic neurons. As a result, sympathetic circuits in [alpha]3 KO mice are silenced. In a second model, 4E-BP genes were deleted ([alpha]3/4E-BP DKO) to examine the role of cap-dependent mRNA translation. Third, to test the role of postsynaptic activity while maintaining functional innervation to sympathetic targets, I generated a novel mouse model in which sympathetic neurons with postsynaptic receptors and those without receptors are randomly intermingled to generate mosaic ganglia. Using this new mouse model, I investigated (a) how preganglionic axons innervate a mosaic population of active and inactive neurons, and (b) how sympathetic neurons develop in the absence of postsynaptic activity when their targets receive functional innervation.When sympathetic circuits are silenced as in [alpha]3 KO mice, dendritic growth is impaired, synapses are mistargeted to the cell soma, and preganglionic axons do not refine. On the other hand, when cap-dependent translation is enhanced, or when their targets receive functional innervation, synaptically silent neurons develop normally without postsynaptic activity. Most strikingly, preganglionic inputs onto these inactive neurons refine in the absence of synaptic transmission. I propose that activity-dependent, target-derived factors play an essential role in the innervation and differentiation of sympathetic neurons. In support of this idea, sympathetic neurons in [alpha]3 KO mice innervate their targets poorly, whereas inactive neurons in mosaic ganglia innervate targets normally. Furthermore, I identified a number of genes whose expression levels were misregulated in synaptically inactive sympathetic neurons of [alpha]3 KO mice, and restored to normal levels in synaptically inactive sympathetic neurons of mosaic mice.My results overturn a widely held belief that the refinement of connections and the extension of dendrites require postsynaptic activity. Insights from my experiments suggest a model in which activity-dependent, target-derived factors mediate dendritic growth, synaptic targeting and refinement, at least in part, by regulating the expression of genes involved in neuronal development and differentiation"--

The Inductive Brain in Development and Evolution provides readers with a substantial biological education on animal nervous systems and their role in the development, adaptation, homeostasis, and evolution of species. The book begins by delving into the embryonic development of the brain and then discusses epigenetic information and neural activity post-birth. It then analyzes the inductive brain’s neural and brain control of such factors like myogenesis, bone development, sensory organs, metamorphosis in vertebrates and invertebrates, and wing development in insects. The book closes with an examination of phenotypic evolution in neural control, mechanisms, and drivers of animal brains. The Inductive Brain in Development and Evolution will offer evolutionary biologists, specifically those researching development, adaptation, and evolution of animals, a comprehensive text that covers a variety of valuable topics. Presents the first book devoted to the inductive role of the brain in development, in adaptation, and in the evolution processes in animals Examines the central nervous system (CNS) from embryonic to adult life stages Provides detailed evidence to investigate the role of the CNS in molding animal morphology and life histories