The end of neurogenesis in the human brain is marked by the transformation of the neural progenitors, the radial glial cells, into astrocytes. This event coincides with the reduction of Reelin expression, a glycoprotein that regulates neuronal migration in the cerebral cortex and cerebellum. A recent study showed that the dentate gyrus of the adult reeler mice, with homozygous mutation in the RELIN gene, have reduced neurogenesis relative to the wild type. Based on the above findings, our first hypothesis states that Reelin expression is important for the formation of radial glia and the generation of neurons from the neural progenitors. In order to investigate the role of Reelin in the process of cortical neurogenesis during development, we used human neural progenitor cells (hNPCs) that were isolated from a fetal cortex. These cells do not express Reelin. In this study, we show that Reelin addition to these hNPCs in vitro induced the formation of radial glia and increased neurogenesis significantly. Next, we investigated the mechanism by which Reelin increases the formation of radial glia and the generation of neurons. The formation of radial glia is under the control of two pathways, these are the Reelin and the Notch-1 signaling pathways. Since the level of Notch-1 activation determines if a cell would become a radial glia or an astrocyte, and since the absence of Reelin allows the transformation of a radial glia into astrocyte, we hypothesized that Reelin induces the formation of radial glia via activating Notch-1 signaling. To test this hypothesis, we investigated the effect of Reelin addition on Notch-1 activation in hNPCs. We found that Reelin addition in vitro activated Notch-1 signaling by increasing the level of Notch-1 intracellular domain (NICD). On the other hand, reducing NICD release, by inhibiting [gamma]-secretase activity, inhibited the Reelin-induced radial glia, confirming that Reelin's effect on the formation of radial glia is dependent on Notch-1 activation. Furthermore, we found that the Reelin-induced tyrosine phosphorylation of Disabled-1 (Dab-1), an adaptor protein downstream of Reelin, and the subsequent activation of Src family kinases, are essential steps for Notch-1 activation by Reelin. Finally, we found that Reelin addition increased the binding of Dab-1, recently identified as a nucleoshuttling protein, to NICD and enhanced NICD translocation to the nucleus. This resulted in the induction of BLBP expression and the subsequent formation of radial glia. Taken together, these data show that Reelin signaling, mediated by Dab-1 and Src kinase, activates Notch-1 signaling in hNPCs resulting in the induction of BLBP expression, the formation of radial glia and the generation of neurons. This work is novel because it provides that first evidence that Reelin expression is an important signal for the neuronal differentiation of the hNPCs. It also shows the crosstalk between Reelin and Notch-1 signaling, two major pathways in development and cell fate determination. The work is significant because it improves our understanding of the role of Reelin signaling in cell fate determination, differentiation and neurogenesis for the future manipulation of these processes to restore adult brain functions after brain injury or in neurodegenerative diseases.

The hippocampal formation plays a critical role in navigation and memory under normal conditions. In pathologies such as Alzheimer's disease and epilepsy, the hippocampus represents one of the first brain regions to suffer damage. When hippocampal development is abnormal, pathological conditions featuring cognitive dysfunction and seizures are common, particularly in children. This publication summarizes new data and relevant findings to a critical understanding of hippocampal development - from anatomy to physiology and from rodents to human. It provides original articles on developmental pathology and on the ongoing role of developmental signaling systems in adults. Broadly, the topics include processes involved in the development of normal or abnormal hippocampus and pathological implications associated with normal or abnormal development, and neurogenesis in an immature or adult hippocampus. Presenting a wide-ranging collection of contributions on hippocampal development, this issue will be of great value for neurobiologists, neurologists, psychiatrists and pediatricians.

Neurogenesis in the adult brain has emerged as one of the most dynamic and rapidly moving fields in modern neuroscience research. The implications of adult neurogenesis for health and well-being are wide-ranging, with findings in this area having distinct relevance for treatment and rehabilitation in neurology and psychopathology. Adult Neurogenesis in the Hippocampus addresses these implications by providing an up-to-date account on how neurogenesis in the adult hippocampus contributes to critical psychological and physiological processes, such as learning and memory, and how it is modified by life experiences, such as aging, environmental enrichment, exercise, and dieting. The book also provides the most current reviews of how adult hippocampal neurogenesis influences the pathogenesis of mood disorders, addiction, and key neurological disorders. This book is the ideal resource for researchers and advanced graduates seeking focused knowledge on the role of adult neurogenesis in brain health and disease. Provides a unique overview of how adult hippocampal neurogenesis contributes to adaptive processes, brain psychopathology, and disease Includes state-of-the-art reviews by leading world experts in adult neurogenesis

The hippocampus is an important brain region, a true central hub for memory of various kinds and other processes. Neuropsychiatric disorders such as Alzheimer's disease, drug addiction, and schizophrenia are characterized by hippocampal alterations. The dentate gyrus of the hippocampus is a site exhibiting adult neurogenesis. This book covers the topic of the hippocampus from various perspectives. It discusses adult neurogenesis, effect of enriched environments on hippocampal plasticity, and long-term potentiation-associated gene expression. The book also addresses multiscale representations of complex environments and strategies in the hippocampus-dependent spatial tasks. Finally, insight into the hippocampus as a link between negative affect and relapse to psychostimulants is provided. The book collects evidence of various hippocampal functions in healthy and disordered brain.

Edited and authored by a wealth of international experts in neuroscience and related disciplines, this key new resource aims to offer medical students and graduate researchers around the world a comprehensive introduction and overview of modern neuroscience. Neuroscience research is certain to prove a vital element in combating mental illness in its various incarnations, a strategic battleground in the future of medicine, as the prevalence of mental disorders is becoming better understood each year. Hundreds of millions of people worldwide are affected by mental, behavioral, neurological and substance use disorders. The World Health Organization estimated in 2002 that 154 million people globally suffer from depression and 25 million people from schizophrenia; 91 million people are affected by alcohol use disorders and 15 million by drug use disorders. A more recent WHO report shows that 50 million people suffer from epilepsy and 24 million from Alzheimer’s and other dementias. Because neuroscience takes the etiology of disease—the complex interplay between biological, psychological, and sociocultural factors—as its object of inquiry, it is increasingly valuable in understanding an array of medical conditions. A recent report by the United States’ Surgeon General cites several such diseases: schizophrenia, bipolar disorder, early-onset depression, autism, attention deficit/ hyperactivity disorder, anorexia nervosa, and panic disorder, among many others. Not only is this volume a boon to those wishing to understand the future of neuroscience, it also aims to encourage the initiation of neuroscience programs in developing countries, featuring as it does an appendix full of advice on how to develop such programs. With broad coverage of both basic science and clinical issues, comprising around 150 chapters from a diversity of international authors and including complementary video components, Neuroscience in the 21st Century in its second edition serves as a comprehensive resource to students and researchers alike.

Comprehensive Overview of Advances in OlfactionThe common belief is that human smell perception is much reduced compared with other mammals, so that whatever abilities are uncovered and investigated in animal research would have little significance for humans. However, new evidence from a variety of sources indicates this traditional view is likely

This volume brings together authors working on a wide range of topics to provide an up to date account of the underlying mechanisms and functions of neurogenesis and synaptogenesis in the adult brain. With an increasing understanding of the role of neurogenesis and synaptogenesis it is possible to envisage improvements or novel treatments for a number of diseases and the possibility of harnessing these phenomena to reduce the impact of ageing and to provide mechanisms to repair the brain.