Throughout the vertebrate lineage, dopaminergic neurons form important neuromodulatory systems that influence motor behavior, mood, cognition, and physiology. Studies in mammals have established that dopaminergic neurons often use γ-aminobutyric acid (GABA) or glutamatergic cotransmission during development and physiological function. Here, we analyze vglut2, gad1b and gad2 expression in combin...

Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease. Here, we demonstrate elevated expression of the...

Ventral tegmental area (VTA) neurons play roles in reward and aversion. The VTA has three major neuronal phenotypes: dopaminergic, GABAergic, and glutamatergic. VTA glutamatergic neurons--expressing vesicular glutamate transporter-2 (VGluT2)--project to limbic and cortical regions, but also excite neighboring dopaminergic neurons. Here, we test whether local photoactivation of VTA VGluT2 neuron...

Midbrain dopaminergic and hindbrain serotonergic neurons play an important role in the modulation of behavior and are involved in a series of neuropsychiatric disorders. Despite the importance of these cells, little is known about the molecular mechanisms governing their development. During embryogenesis, midbrain dopaminergic neurons are specified rostral to the midbrain-hindbrain organizer (M...

Although substantia nigra dopaminergic neurons are spontaneously active both in vivo and in vitro, this activity does not depend on afferent input as these neurons express an endogenous calcium-dependent oscillatory mechanism sufficient to drive action potential generation. However, afferents to these neurons, a large proportion of them GABAergic and arising from other nuclei in the basal gangl...

CASK is an evolutionarily conserved scaffolding protein that has roles in many cell types. In Drosophila, loss of the entire CASK gene or just the CASK-β transcript causes a complex set of adult locomotor defects. In this study, we show that the motor initiation component of this phenotype is due to loss of CASK-β in dopaminergic neurons and can be specifically rescued by expression of CASK-β w...

Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors-notably nu...

Dopaminergic neurons represent less than 1% of the total number of neurons in the brain. This low amount of neurons regulates important brain functions such as motor control, motivation, and working memory. Nigrostriatal dopaminergic neurons selectively degenerate in Parkinson's disease (PD). This progressive neuronal loss is unequivocally associated with the motors symptoms of the pathology (b...

BACKGROUND Human embryonic stem cells (hESCs) may provide an invaluable resource for regenerative medicine. To move hESCs towards the clinic it is important that cells with therapeutic potential be reproducibly generated under completely defined conditions. METHODOLOGY/PRINCIPAL FINDINGS Here we report a four-step scalable process that is readily transferable to a Good Manufacture Practice (G...

DOPAMINE IN THE ADULT CNS The developmental functions mediated by dopaminergic signaling are not currently fully appreciated, however, more is known about the influences of DA in the mature brain. Synthesis of DA involves conversion of the amino acid L-tyrosine into L-dopa by the rate-limiting enzyme tyrosine hydroxylase (TH). Subsequent activity of DOPA decarboxylase results in final conversio...