Development of Neural Circuitry

Development of Neural Circuitry PDF

Author:

Publisher: Academic Press

Published: 2009-05-07

Total Pages: 253

ISBN-13: 0080922619

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The nervous system is highly complex both in its structural order and in its ability to perform the many functions required for survival and interaction with the environment; understanding how it develops has proven to be one of the greatest challenges in biology. Such precision demands that key events at every developmental stage are executed properly and are coordinated to produce the circuitry underlying each of the adult nervous system's functions. This volume describes the latest research on the cellular and molecular mechanisms of neural circuitry development, while providing researchers with a one-stop overview and synthesis of contemporary thought in the area. Reviews current research findings on the development of neural circuitry, providing researchers with an overview and synthesis of the latest contemporary thought in the cellular and molecular mechanisms that underlie the development of neural circuitry Includes chapters discussing topics such as the guidance of nerve growth and the formation of plasticity of synapses, helping researchers better understand underlying mechanisms of neural circuit development and maintenance that may play a role in such human diseases/conditions as depression, anxiety, and pain Chapters make use of a variety of human and animal models, allowing researchers to compare and contrast neural circuitry development across a wide spectrum of models

Investigation of the Molecular Mechanisms that Mediate Neural Circuit Formation

Investigation of the Molecular Mechanisms that Mediate Neural Circuit Formation PDF

Author: Katherine Watters

Publisher:

Published: 2016

Total Pages: 38

ISBN-13:

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Thought, perception, and behavior rely on the faithful transfer of information between neurons, the cells of the nervous system. To ensure proper neural circuit formation, neurons must form connections with the proper neuronal partner, a process called synaptic partner recognition. Next, the neuron must recruit synaptic components to the correct membrane, a process called synaptic assembly. These two processes must be tightly linked for proper nervous system function, and defects in either may result in developmental neurological disorders. The VanHoven laboratory uses the genetic model organism Caenhorabditis elegans and the transgenic fluorescent marker NLG-1 GRASP. NLG-1 GRASP fluorescently labels synapses that form between the PHB chemosensory neurons and the AVA interneurons in vivo. Previously the VanHoven laboratory revealed that the ligand-receptor pair UNC-6/Netrin and UNC-40/DCC act in a juxtacrine manner to specify synaptic partner recognition between PHB and AVA neurons. Here, we study two other genes required in neural circuit formation: the transmembrane receptor clr-1/Receptor Protein Tyrosine Phosphatase (RPTP) and the small vesicle transporter protein unc-69/Small Coiled-Coil (SCOCO). We find that both CLR-1/RPTP and UNC-69/SCOCO are required for proper PHB to AVA synaptogenesis, act in the previously described UNC-6/Netrin UNC-40/DCC pathway, and likely function downstream of UNC-6/Netrin. Further characterization of how CLR-1/RPTP and UNC-69/SCOCO mediate nervous system development will help us to understand the logic of neural circuit formation as well as aid in the development of treatments for neurological disorders.

Neural Plasticity and Memory

Neural Plasticity and Memory PDF

Author: Federico Bermudez-Rattoni

Publisher: CRC Press

Published: 2007-04-17

Total Pages: 368

ISBN-13: 1420008412

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A comprehensive, multidisciplinary review, Neural Plasticity and Memory: From Genes to Brain Imaging provides an in-depth, up-to-date analysis of the study of the neurobiology of memory. Leading specialists share their scientific experience in the field, covering a wide range of topics where molecular, genetic, behavioral, and brain imaging techniq

Novel Genetic Strategies to Probe Mechanisms Underlying Neuronal Development and Circuit Formation

Novel Genetic Strategies to Probe Mechanisms Underlying Neuronal Development and Circuit Formation PDF

Author: Benjamin Throesch

Publisher:

Published: 2020

Total Pages: 145

ISBN-13:

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The brain is a complex organ that contains hundreds of diverse cellular subtypes which organize into unique regions and build intricate neural circuits. Neurons all transition through developmental stages where they must specify into cellular subtypes, migrate to appropriate brain regions, and extend axons to innervate postsynaptic targets as well as elaborate dendritic trees to receive incoming information. These stages are shaped by a balance of intracellular transcriptional programs and extracellular signals such as guidance molecules, adhesion proteins, and neuronal activity. While an extensive list of factors contributing to these processes has been catalogued, the details remain unclear on how they converge within a cell to direct its development. Therefore, we developed novel genetic systems to decipher the rules that shape neuronal development and circuit formation. In one set of studies, we selectively blocked synaptic activity from a subset of neurons within the rodent olfactory bulb to investigate their role in shaping olfactory circuit development. We observed a dramatic impact on the maturation of newborn inhibitory neurons which could not be completely rescued by inhibiting cell death. By assessing the transcriptome of these developmentally-stalled neurons, we identified gene networks that regulate the maturation and integration of neurons into established circuits. For the second set of experiments, we injected rat stem cells into mouse blastocysts to generate rat-mouse brain chimeras and determine whether rat neurons are flexible to develop into, and contribute to foreign neural circuits. In brain-complemented chimeras, we observed diverse rat neuronal subtypes that adopt their host's developmental timeline and functionally integrate into the mouse brain. Furthermore, we identified species-specific barriers to rat complementation when these neurons are challenged to reconstitute degenerated mouse circuits. Together, these studies provide insights into the mechanisms governing neuronal integration into foreign and compromised neural circuits, which will inform efforts in regenerative medicine.

From Neurons to Neighborhoods

From Neurons to Neighborhoods PDF

Author: National Research Council

Publisher: National Academies Press

Published: 2000-11-13

Total Pages: 610

ISBN-13: 0309069882

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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 Circuits of Innate Behaviors

Neural Circuits of Innate Behaviors PDF

Author: Hao Wang

Publisher: Springer Nature

Published: 2020-08-27

Total Pages: 112

ISBN-13: 9811570868

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This book summarizes the latest research findings in the neurocircuitry of innate behaviors, covering major topics such as innate fear, aggression, feeding, reward, social interaction, parental care, spatial navigation, and sleep-wake regulation. For decades, humans have been fascinated by wild animals’ instincts, like the annual two-thousand-mile migration of the monarch butterfly in North American, and the “imprint” behavior of newborn birds. Since these instincts are always displayed in stereotypical patterns in most individuals of a given species, the neural circuits processing such behaviors must be genetically hard-wired in the brain. Recently, with the development of modern techniques, including optogenetics, retrograde and anterograde virus tracing, and in vivo calcium imaging, researchers have been able to determine and dissect the specific neural circuits for many innate behaviors by selectively manipulating well-defined cell types in the brain. This book discusses recent advances in the investigation of the neural-circuit mechanisms underlying innate behaviors.

Molecular Mechanisms of Memory Formation

Molecular Mechanisms of Memory Formation PDF

Author: Kartik Ramamoorthi

Publisher:

Published: 2014

Total Pages: 238

ISBN-13:

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A fundamental goal in neuroscience is to understand mechanisms underlying the ability to create memories from sensory experience. While large structures such as the hippocampus are known to be critical for certain types of learning, memories are ultimately thought to be represented in sparsely distributed neuronal ensembles within these larger structures. Currently, there are few tools that allow for the identification and manipulation of these ensembles, which has limited our understanding of the molecular and cellular processes underlying learning and memory. We have previously reported that the activity-regulated transcription factor Npas4 is selectively induced in a sparse population of CA3 following contextual fear conditioning. Global knockout or selective deletion of Npas4 in CA3 both resulted in impaired contextual memory, and restoration of Npas4 in CA3 was sufficient to reverse the deficit in global knockout mice. Taking advantage of the critical role of Npas4 in contextual memory formation, we developed a set of novel molecular tools to gain access to cell populations activated by experience. Using this system, we identified and manipulated the properties of neurons activated by behavioral experience in a variety of neural circuits in mice, rats, and Drosophila. We believe that the tools developed in this thesis can provide a major advancement in the field, and will allow researchers to target any neural circuit activated by experience in a variety of species.

Pharmacological Regulation of Neural Circuit Formation in HIPSC-Derived Neurons and 'Mini-Brains'.

Pharmacological Regulation of Neural Circuit Formation in HIPSC-Derived Neurons and 'Mini-Brains'. PDF

Author: Taylor L Rudisill

Publisher:

Published: 2018

Total Pages: 87

ISBN-13:

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Emerging evidence suggests that altered neural connectivity, particularly at the level of synaptic connections, contributes to the pathology of many neurodevelopmental and neurodegenerative diseases. For instance, post-mortem Autistic patient brain samples have increased numbers of excitatory to inhibitory synaptic connections, referred to as an E/I imbalance [42]. Contrastingly, post-mortem brain samples from patients diagnosed with Alzheimer's disease have decreased numbers of synaptic connections [42]. In order to understand the mechanisms that underlie the formation of these synaptic circuits, we develop 3-D human cortical organoids ('mini-brains') from human-induced pluripotent stem cells (hIPSCs). Previous research demonstrates that rearrangements of the actomyosin cytoskeleton drive neural circuit formation, in particular the development and maturation of actin-enriched spines at excitatory synapses. This thesis work investigates how pharmacological regulation of actomyosin activity affects neuronal connectivity during neurite formation in 2-D and excitatory synapse formation in 3-D 'mini-brains'. The Rho-Kinase (ROCK) inhibitor, Y-27632, both inhibits non-muscle myosin II (NM-II) and leads to a corresponding increase in Rac-driven actin polymerization. In 2-D, Y-27632 promotes neurite formation. Specifically, Y-27632 increases the number, length, and branching of neurites in hIPSC-derived neurons. Furthermore, Y-27632 increases neurite persistence, while decreasing neurite protrusion and retraction rates. However, in 3-D, acute Y-27632 treatment increases excitatory synapse area, consistent with an increase in Rac-driven actin polymerization [39]. Thus, Y-27632 increases both neurite outgrowth and excitatory synapse formation and may serve as a potential therapeutic for neurodegenerative diseases associated with synapse loss such as Alzheimer's disease. This study demonstrates the need for physiologically-relevant brain models, such as 3-D cortical organoids, to assess the impact of drug therapies on developing neural circuits to potentially treat neurodevelopmental and neurodegenerative disorders.