The molecular mechanisms, which are responsible for the functional differences between the various types of neuronal synapses, have become one of the central themes of modern neurobiology. It is becoming increasingly clear that a misregulation of synaptogenesis and synaptic remodeling and dysfunctional neuronal synapses are at the heart of several human diseases, both neurological disorders and psychiatric conditions. As synapses present specialized cellular junctions between neurons and their target cells, it may not come as a surprise that neural cell adhesion molecules (CAMs) are of special importance for the genesis and the maintenance of synaptic connections. Genes encoding adhesive molecules make up a significant portion of the human genome, and neural CAMs even have been postulated to be a major factor in the evolution of the human brain. These are just some of the many reasons why we thought a book on neural CAMs and their role in establishing and maintaining neuronal synapses would be highly appropriate for summarizing our current state of knowledge. Without question, over the near future, additional adhesive proteins will join the ranks of synaptic CAMs and our knowledge, and how these molecules enable neurons and their targets to communicate effectively will grow.

In the evolutionary transition from unicellular to multicellular organisms, single cells assemble into highly organized tissues and cooperatively carry out physiological functions. To act as an integrated system, individual cells communicate with each other extensively through signaling at the cellular interface. Cell-surface signaling thus controls almost every aspect of the development and physiology of multicellular organisms. Taking the nervous system as an example, cell-surface wiring molecules dictate the precise assembly of the neural network during development, while neurotransmitter receptors and ion channels mediate synaptic transmission and plasticity in adults. Delineating the cell-surface signaling is therefore crucial for understanding the organizing principles and operating mechanisms of multicellular systems. My dissertation research integrates method development and mechanistic interrogation to investigate cell-surface signaling in neural circuit assembly. My collaborators and I developed, for the first time to my knowledge, a method for quantitatively profiling cell-surface proteomes in intact tissues with cell-type and spatiotemporal specificities. Applying this method to Drosophila olfactory projection neurons (PNs), I captured cell-surface proteomes of developing and mature PNs and observed globally coordinated dynamics of PN surface proteins corresponding to the wiring and functional stages of the olfactory circuit, providing the first systemic view on how neuronal surface evolves in development. A proteome-instructed in vivo screen identified 20 new cell-surface molecules regulating neural circuit assembly, many of which belong to evolutionarily conserved protein families not previously linked to neural development. These discoveries highlight the power of this new method in uncovering new regulators of brain wiring. Notably, this method should be readily applicable for profiling proteins on the surface of other cell types, tissues, and organisms, far beyond the fly olfactory circuit. In a complementary set of studies on the Plexin B receptor, I developed a generalizable protein tagging approach that reveals cell-type-specific endogenous protein distribution in vivo. Combining this tagging approach and genetic analyses, we found that the Plexin B receptor uses multiple molecular strategies: temporally-regulated protein distribution, level-dependent signaling, and divergent engagement of signaling motifs, to sequentially instruct several distinct steps of axon targeting. These include axon-axon interaction, axon guidance, and synaptic partner selection. Our findings illustrate how a single molecule achieves multi-functionality while preserving its signal specificity in brain wiring. In summary, this dissertation combines quantitative multi-omic profiling and in vivo mechanistic interrogation to elucidate the systemic properties and molecular bases of cell-surface signaling underlying the precise wiring of neural circuits.

Understanding the molecular and cellular mechanisms underlying the development of specific neural circuits is not just an intellectual curiosity but also central to our ability to develop therapeutic approaches to repair damaged pathways in the future. In Neural Development: Methods and Protocols, experts in the field contribute commonly used protocols to facilitate future research in developmental neuroscience. Split into four convenient sections, this detailed volume covers techniques of culturing neurons and glia as well as their growth and differentiation, methods of gene delivery and down regulation, protocols for analyzing axon growth and guidance plus synapse formation, and, finally, basic methods to analyze brain morphology and axon pathways in developing animals. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and accessible, Neural Development: Methods and Protocols provides key guidance for students and postdoctoral fellows new to developmental neurobiology.

Fundamental Neuroscience, Third Edition introduces graduate and upper-level undergraduate students to the full range of contemporary neuroscience. Addressing instructor and student feedback on the previous edition, all of the chapters are rewritten to make this book more concise and student-friendly than ever before. Each chapter is once again heavily illustrated and provides clinical boxes describing experiments, disorders, and methodological approaches and concepts.Capturing the promise and excitement of this fast-moving field, Fundamental Neuroscience, 3rd Edition is the text that students will be able to reference throughout their neuroscience careers! 30% new material including new chapters on Dendritic Development and Spine Morphogenesis, Chemical Senses, Cerebellum, Eye Movements, Circadian Timing, Sleep and Dreaming, and Consciousness Additional text boxes describing key experiments, disorders, methods, and concepts Multiple model system coverage beyond rats, mice, and monkeys Extensively expanded index for easier referencing

Significant advances in brain research have been made, but investigators who face the resulting explosion of data need new methods to integrate the pieces of the "brain puzzle." Based on the expertise of more than 100 neuroscientists and computer specialists, this new volume examines how computer technology can meet that need. Featuring outstanding color photography, the book presents an overview of the complexity of brain research, which covers the spectrum from human behavior to genetic mechanisms. Advances in vision, substance abuse, pain, and schizophrenia are highlighted. The committee explores the potential benefits of computer graphics, database systems, and communications networks in neuroscience and reviews the available technology. Recommendations center on a proposed Brain Mapping Initiative, with an agenda for implementation and a look at issues such as privacy and accessibility.

Based on advances in biotechnology and neuroscience, non-invasive neuromodulation devices are poised to gain clinical importance in the coming years and to be of increasing interest to patients, clinicians,health systems, payers, and industry. Evidence suggests that both therapeutic and non-therapeutic applications of non-invasive neuromodulation will continue to expand in coming years, particularly for indications where treatments are currently insufficient, such as drug-resistant depression. Given the growing interest in non-invasive neuromodulation technologies, the Institute of Medicine's Forum on Neuroscience and Nervous System Disorders convened a workshop, inviting a range of stakeholders - including developers of devices and new technologies, researchers, clinicians, ethicists, regulators, and payers - to explore the opportunities, challenges, and ethical questions surrounding the development, regulation, and reimbursement of these devices for the treatment of nervous system disorders as well as for non-therapeutic uses, including cognitive and functional enhancement. This report highlights the presentation and discussion of the workshop.