Dopaminergic Neurons

Theneurotransmitter dopamine has just celebrated its 50thbirthday. The discovery of dopamine as a neuronal entity in the late 1950s and the notion that it serves in neurotransmission has been a milestone in the field of neuroscience research. This milestone marked the beginning of an era that explored the brain as an integrated collection of neuronal systems that one could distinguish on basis of neurotransm- ter identities, and importantly, in which one started to be able to pinpoint the seat of brain disease. The mesodiencephalic dopaminergic (mdDA) system, previously designated as midbraindopaminergic system, has received much attention since its discovery. The initial identification of dopamine as a neurotransmitter in the central nervous system (CNS) and its relevance to psychiatric and neurological disorders have stimulated a plethora of neurochemical, pharmacological and genetic studies into the function of dopamine neurons and theirprojections. In the last decade, studies on gene expression and development have further increased the knowledge of this neuronal population and have unmasked a new level of complexity. The start of the molecular dissection of the mdDA system has been marked by the cloning and characterization ofNurrl and Pitx3. These transcription factors were shown to have a critical function during mdDA development. These initial studies have been followed by the identification of many other proteins, which have a crucial function in the creation of a dopamine neuron permissive region, induction of precursors, induction of terminaldifferent- tion and finally maintenance of the mdDA neuronal pool.

This book provides a unique and timely multidisciplinary synthesis of our current knowledge of the anatomy, pharmacology, physiology and pathology of the substantia nigra pars compacta (SNc) dopaminergic neurons. The single chapters, written by top scientists in their fields, explore the life cycle of dopaminergic neurons from their birth to death, the cause of Parkinson's disease, the second most common and disabling condition in the elderly population. Nevertheless, the intracellular cascade of events leading to dopamine cell death is still unknown and, consequently, treatment is symptomatic rather than preventive. The mechanisms by which alterations cause neuronal death, new therapeutic approaches and the latest evidence of a possible de novo neurogenesis in the SNc are reviewed and singled out in different chapters. This book bridges basic science and clinical practice and will prepare the reader for the next few years, which will surely be eventful in terms of the progress of dopamine research.

This volume provides a variety of technical approaches to study dopamine system function and dysfunction. Chapters guide readers through dopamine release in ex vivo and freely moving animals, multi-recording devices for in vivo simultaneous single cell and population activity, in silico modeling of dopamine neurons activity, neuroanatomical approaches, unbiased stereology, ultrastructural analyses of dopaminergic neurons, and axonal innervation. Additionally, chapters also incorporate pharmacological tools to model neuropsychiatric diseases, novel behavioral paradigms to dissect dopamine's role in behavior, and functional imaging to follow human dopamine system development. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Comprehensive and cutting-edge, Dopamine Neurotransmission aims to be a valuable resource for researchers in various disciplines.

The proceedings of the 1987 IUPHAR symposium held in Sydney, Australia are fully documented. Over 100 scientists from 16 countries attended the three-day conference, during which time 68 multi-disciplinary presentations concerning dopamine systems and their regulation were made.

This book is the culmination of fifteen years of research on the transplantation of dopaminergic neurons in the striatum of the weaver mouse (wv/wv), a neurological mutant characterized by genetically-determined degeneration of midbrain dopamine neurons. This mutant constitutes the only available laboratory model with a chronic disorder that mimics Parkinson's disease. Structural and functional aspects of intrastriatal mesencephalic neuron grafting into the weaver model are reviewed, including histochemical correlates of graft survival and integration, numerical aspects of donor cell survival, ultrastructural findings on synaptogenesis, neurochemical indices of dopamine uptake and receptor binding, gene expression of structural and neurotransmitter-receptor related molecules, levels of striatal amino acid receptors, and behavioural effects of unilateral and bilateral neuronal transplantations.

This comprehensive reference provides a detailed overview of current concepts regarding the cause of Parkinson's disease-emphasizing the issues involved in the design, implementation, and analysis of epidemiological studies of parkinsonism.

With contributions by numerous experts