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The tremendous diversity of neuronal cell types enables the assembly of neural circuitry that generates and shapes complex behaviors. In contrast to the intense focus on understanding the gene regulatory programs that specify different neuron types, the programs that guide their maturation have received far less attention. Here we show the embryonic maturation of serotonergic (5-HT) neurons, and the role of the transcription factor, PET-1 in driving this maturational program. Initally we undertook a series of experiments to define PET-1's function in development and the early postnatal period. To this end, we used RNA-Seq in flow sorted fetal YFP+ 5-HT neurons obtained from the rostral hindbrain to identify specific temporal gene expression patterns found in maturing 5-HT neurons from E11.5 to shortly after birth (P1-P3). We found that genes downregulated from E11.5 to birth were genes associated with basic cellular processes, while genes upregulated were associated with maturing neural identity and function. Next we compared the expression profile of E15.5 +/+ and Pet-1-/- 5-HT neurons. Expression of over 800 genes was diminished 1.5-40 fold, and greater than 1000 genes were derepressed 1.5-13 fold in Pet-1-/- 5-HT neurons. Gene ontology shows that PET-1 is a regulator of diverse pathways including cell synaptic development and function, axon and dendrite development, and neural transmission. The role of PET-1's in driving maturation of genes involved in neuronal excitability was verified by single cell recording of 5-HT neurons. Aditionally, PET-1 was found to regulate the glutamatergic AMPA receptor subunit Gria4, the alpha adrenergic receptor 1b, Adra1b, and the lysophosphtidic acid receptor 1, Lpar1. This was verified by in situ hybridization, immunohistochemistry, and electorphysiological recordings. Finally, to ascertain PET-1's postnatal function, we deleted Pet-1 in the early postnatal period using the Cre/loxP system. This revealed PET-1 switches its focus on regulating genes needed for 5-HT synthesis to those needed for neuronal activity. Finally, we used ChIP-seq to identify PET-1 direct targets. We found PET-1 binds within or proximal to 25-30% of PET-1 upregulated and down regulated genes, suggesting direct transcriptional activation and repression of PET-1 is required for correct 5-HT development.
This volume covers aspects of sudden infant and early childhood death, ranging from issues with parental grief, to the most recent theories of brainstem neurotransmitters. It also deals with the changes that have occurred over time with the definitions of SIDS (sudden infant death syndrome), SUDI (sudden unexpected death in infancy) and SUDIC (sudden unexpected death in childhood). The text will be indispensable for SIDS researchers, SIDS organisations, paediatric pathologists, forensic pathologists, paediatricians and families, in addition to residents in training programs that involve paediatrics. It will also be of use to other physicians, lawyers and law enforcement officials who deal with these cases, and should be a useful addition to all medical examiner/forensic, paediatric and pathology departments, hospital and university libraries on a global scale. Given the marked changes that have occurred in the epidemiology and understanding of SIDS and sudden death in the very young over the past decade, a text such as this is very timely and is also urgently needed.
Handbook of the Behavioral Neurobiology of Serotonin, Second Edition, builds on the success of the first edition by continuing to provide a detailed and comprehensive overview of the many facets of behavioral serotonin research. The text expands on the two key topics, behavioral control (sensory processing, ultrasonic vocalization, and melatonin and sleep control) and psychiatric disorders, including its role on psychostimulant abuse and addiction. The new edition includes two new sections on the serotonin systems interactions and the involvement of serotonin in neurological disorders and associated treatment. Serotonin is a major neurotransmitters in the serotonergic system which one of the best studied and understood transmitter systems. Both are critically involved in the organization of all behaviors and in the regulation of emotion and mood. Features two new sections on serotonin systems interactions and serotonin in neurological disorders Focuses on ionotropic and metabotropic 5-HT receptor involvement in behavior Maps receptors and receptor signaling pathways to neurochemical and behavioral outcomes Covers the interactions between serotonin, melatonin and kynurenine pathways
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This volume covers aspects of sudden infant and early childhood death, ranging from issues with parental grief, to the most recent theories of brainstem neurotransmitters. It also deals with the changes that have occurred over time with the definitions of SIDS (sudden infant death syndrome), SUDI (sudden unexpected death in infancy) and SUDIC (sudden unexpected death in childhood). The text will be indispensable for SIDS researchers, SIDS organisations, paediatric pathologists, forensic pathologists, paediatricians and families, in addition to residents in training programs that involve paediatrics. It will also be of use to other physicians, lawyers and law enforcement officials who deal with these cases, and should be a useful addition to all medical examiner/forensic, paediatric and pathology departments, hospital and university libraries on a global scale. Given the marked changes that have occurred in the epidemiology and understanding of SIDS and sudden death in the very young over the past decade, a text such as this is very timely and is also urgently needed.
Serotonin - A Chemical Messenger Between All Types of Living Cells is a very interesting book on the most ancient neurotransmitter, hormone and trophic factor serotonin or 5-hydroxytryptamine (5-HT). This unique chemical is present in all living cells including plants and animals. This book will take us through a serene journey of the evolutionary history of serotonin and its role from man to mollusk. There are many interesting chapters incorporated in this book, including novel approaches for detecting minor metabolites of serotonin in human plasma, production and function of serotonin in cardiac cells, immuno-thrombotic effects of serotonin in platelets to the identification and localization of serotonin in the nervous system and gonad of bivalve mollusks.
The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.
Marijuana is the most commonly used psychotropic drug in the United States, after alcohol. With the legalization and decriminalization of cannabis, momentum continues to build and propelled by the reduction of stigma associated to its consumption, there is growing concern regarding the long-term impact on brain function and behavior. Cannabis and the Developing Brain aims to provide comprehensive research on the effects of cannabis during neurodevelopment stages (i.e., perinatal and adolescent ages). This book introduces readers to vivo neural circuits, molecular and cellular mechanisms affected by cannabis exposure during three different temporal windows of brain vulnerability. Second, it offers a unique insight to shared neurobiological features of cannabinoid exposure during different developmental periods. Lastly, Cannabis and the Developing Brain determines the adverse impact of developmental cannabinoid exposure on specific cognition, emotion and behaviors. Reviews exposure effects on different areas and circuits of the brain Identifies effects of exposure at prenatal, perinatal, infant, and adolescent ages Includes cannabis interaction with known genetic and environmental risk factors Contains neurodevelopment and neuropsychiatric disorders associated with cannabis exposure