Pet 1 Switches Transcriptional Targets Postnatally To Regulate Maturation Of Serotonin Neuron Excitability

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

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

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.

This book is a comprehensive monograph on the CtBP family proteins. These proteins are gaining wide scientific interest due to their critical roles in animal development and in oncogenesis. The CtBP family proteins are multifunctional. They predominantly function as transcriptional corepressors in the nucleus by recruiting various histone modifying enzymes such as histone deacetylases, histone methylases and a histone demethylase. They also perform several diverse cytosolic functions such as Golgi maintenance and in central nervous system synapses.

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.