Neuronal migration, a key event during brain development, remains largely unexplored in the mesencephalon, where dopaminergic (DA) and GABA neurons constitute two major neuronal populations. Here we study the migrational trajectories of DA and GABA neurons and show that they occupy ventral mesencephalic territory in a temporally and spatially specific manner. Our results from the Pitx3-deficien...

Efficient clearance of dopamine (DA) from the synapse is key to regulating dopaminergic signaling. This role is fulfilled by DA transporters (DATs). Recent advances in the structural characterization of DAT from Drosophila (dDAT) and in high-resolution imaging of DA neurons and the distribution of DATs in living cells now permit us to gain a mechanistic understanding of DA reuptake events in si...

Parkinson's disease is characterized by a loss of dopaminergic nigrostriatal neurons. This neuronal loss is mimicked by the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). MPP+ toxicity is mediated through inhibition of mitochondrial complex I, decreasing ATP production, and upregulation of oxygen radicals. There is evidence that the cell death induced by MPP+ is apoptotic and that inhibition of...

In the present study, we characterized the intrinsic electrophysiological properties and the membrane currents activated by dopamine (DA) D(2) and GABA(B) receptors in midbrain dopaminergic neurons, maintained in vitro in a slice preparation, from wild-type and homozygous weaver (wv/wv) mice. By using patch-clamp techniques, we found that membrane potential, apparent input resistance, and spont...

Substitution of degenerated dopaminergic (DA) neurons by intrastriatally transplanted ventral mesencephalon (VM)-derived progenitor cells has been shown to improve motor functions in parkinsonian patients and animal models, whereas investigations of electrophysiological properties of the grafted DA neurons have been rarely performed. Here we show electrophysiological properties of grafted VM pr...

The human substantia nigra (SN) is thought to consist of two functionally distinct neuronal populations-dopaminergic (DA) neurons in the pars compacta subregion and GABA-ergic neurons in the pars reticulata subregion. However, a functional dissociation between these neuronal populations has not previously been demonstrated in the awake human. Here we obtained microelectrode recordings from the ...

Dopaminergic (DA) neurons represent <0.01% of neurons in the human brain, but are essential for normal neurological and psychiatric function. The majority of these neurons reside in the ventral midbrain, but they exert their profound influences on brain function through projections to both the cortex and the basal ganglia. These projections secrete dopamine from small clear synaptic vesicles (S...

The neurology of male sexuality has been poorly studied owing to difficulties in studying brain circuitry in humans. Dopamine (DA) is essential for both physiological and behavioural responses, including the regulation of sexuality. Previous studies have revealed that alterations in DA synthesis in dopaminergic neurons can induce male-male courtship behaviour, while increasing DA levels in the ...

To begin to identify novel protein(s) that acts on nigral dopaminergic (DA) neurons, we characterized trophic effects of DA-depleted striatum on survival of fetal DA neurons in the present study. Treatment of ventral mesencephalic cultures with the striatal extracts delayed DA cell death in a dose-dependent manner. This effect was partially dependent on brain-derived neurotrophic factor (BDNF),...

For many years, several studies have been conducted to investigate the effect of stress on the onset of Parkinson’s disease (PD), which is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). de Pablos et al. reported that stressed animals were associated with a higher rate of death of dopaminergic neurons in the substantia nigra, and that this ef...