Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1-/- mice showed hypolocomotion when subjecte...

The dopaminergic D3 receptor (D3R) is emerging as an antagonist of sensitized behavior induced by addictive drugs such as cocaine. New work by Wang and coworkers in this issue of Neuron now identifies CaMKII as an important negative regulator of the D3R. CaMKII relieves the D3R-mediated inhibition on sensitized behavior to foster drug-seeking behavior.

Parkinson’s disease (PD) is a progressive neurodegenerative disease due to dopaminergic neuron degeneration within the Substantia Nigra. According to the Parkinson’s Disease Foundation, as many as one million Americans live with Parkinson’s disease and approximately sixty thousand are diagnosed with PD each year. Although there are a number of treatment options available for the symptoms that a...

How the cholinergic and dopaminergic systems of the striatum interact and how these interface with the massive neocortical input to the striatum are classic questions of cardinal interest to neurology and psychiatry. In this issue of Neuron, Ding and colleagues show that a key to these puzzles lies in the thalamic inputs to the striatum targeting its cholinergic interneurons.

The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons by analysing the phenotype of Foxa1 an...

Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. PARK2 mutations cause early-onset forms of PD. PARK2 encodes an E3 ubiquitin ligase, Parkin, that can selectively translocate to dysfunctional mitochondria to promote their removal by autophagy. However, Parkin knockout (KO) mice do not display signs of neurodegeneration. ...

Asymmetric cell divisions are required for cellular diversity and defects can lead to altered daughter cell fates and numbers. In a genetic screen for C. elegans mutants with defects in dopaminergic head neuron specification or differentiation, we isolated a new allele of the transcription factor HAM-1 [HSN (Hermaphrodite-Specific Neurons) Abnormal Migration]. Loss of both HAM-1 and its target,...

Catastrophic loss of dopaminergic neurons is a hallmark of Parkinson's disease. Despite the recent identification of genes associated with familial parkinsonism, the etiology of most Parkinson's disease cases is not understood. Environmental toxins, such as the herbicide paraquat, appear to be risk factors, and it has been proposed that susceptibility is influenced by genetic background. The ge...

The hallmark of Parkinson's disease is on-going degeneration of dopaminergic neurons in the substantia nigra, which may be due to various etiologies. Various approaches to alleviate symptoms are available, such as life-long pharmacological intervention, deep brain stimulation, and transplantation of dopaminergic neuron-containing fetal tissue. However, each of these approaches has a disadvantag...

Dopamine is crucial for habit learning. Activities of midbrain dopaminergic neurons are regulated by the cortical and subcortical signals among which glutamatergic afferents provide excitatory inputs. Cognitive implications of glutamatergic afferents in regulating and engaging dopamine signals during habit learning, however, remain unclear. Here, we show that mice with dopaminergic neuron-speci...