Parkinson's disease (PD) is characterized by the selective loss of nigral dopaminergic (DA) neurons, which have long axons enriched with microtubules. Depolymerization of microtubules by PD toxins such as rotenone disrupts vesicular transport. The ensuing accumulation of vesicles in the cell body leads to increased cytosolic concentration of dopamine due to leakage of the vesicles. Elevated oxi...

An anomaly in the experimental data underlying the theory that neuroleptics act by blockade of dopaminergic neurotransmission is the repeatedly demonstrated failure in several laboratories of parenterally administered neuroleptics to antagonize electrophysiologic actions of locally applied dopamine (DA) in striatum. This failure is enigmatic since many investigators have successfully demonstrat...

Dopamine-deficient (DD) mice cannot synthesize dopamine (DA) in dopaminergic neurons due to selective inactivation of the tyrosine hydroxylase gene in those neurons. These mice become hypoactive and hypophagic and die of starvation by 4 weeks of age. We used gene therapy to ascertain where DA replacement in the brain restores feeding and other behaviors in DD mice. Restoration of DA production ...

BACKGROUND PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathwa...

The main pathological hallmark in Parkinson’s disease (PD) is the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN), affecting movements such as walking, talking and writing. Today, there is no cure available for PD and existing treatments only provide symptomatic relief, but the prospect of using stem cell based cell replacement therapies for patients with PD have prov...

A growing body of evidence suggests that teleosts are important models for the study of neural processing of olfactory information, and the functional role of dopamine (DA), which is a potent neuromodulator endogenous to the mammalian olfactory bulb, has been one of the strongest focuses in this field. However, the cellular mechanisms of dopaminergic neuromodulation in olfactory bulbar neural c...

Ret is the common signaling receptor for glial cell line-derived neurotrophic factor (GDNF) and other ligands of the GDNF family that have potent effects on brain dopaminergic neurons. The Met918Thr mutation leads to constitutive activity of Ret receptor tyrosine kinase, causing the cancer syndrome called multiple endocrine neoplasia type B (MEN2B). We used knock-in MEN2B mice with the Ret-MEN2...

A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA) neurons are reciprocally connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational s...

To examine the intrinsic properties of postnatal mesolimbic dopamine (DA) neurons, we dissociated the ventral tegmental area (VTA) from postnatal rats, enriched for DA neurons by microdissection or gradient purification, and grew the cells in culture. In these cultures, up to 50% of neurons were dopaminergic. DA neurons resembled their in vivo counterparts in soma shapes, and in showing two lev...

Recent pharmacological discovery on trace amineassociated receptor, type 1(TAAR1) has emphasized importance of trace amines in pathogenesis of psychoses, such as schizophrenia. TAAR1 has many ligands, including tyramine, β-phenylethylamine (PEA), amphetamines, and 3’-iodothyronamine. Socalled D-neurons are putative producer of trace amines, endogenous ligands of TAAR1. The D-neuron is defined “...