This scientific commentary refers to ‘Cav1.3 channels control D2 autoreceptor responses via NCS1 in substantia nigra dopamine neurons’ by Dragicevic et al. (doi:10.1093/brain/awu131).
Appropriate activity of substantia nigra dopamine neurons is required for proper motor function, habit formation and motivation, and degeneration of these neurons in Parkinson’s disease leads to disrupted control of voluntary movement. In this issue of Brain, Dragicevic et al. unite two previously separate lines of research on the regulation of substantia nigra dopamine neuron activity—one based on L-type calcium channels and the other on D2 autoreceptors—and suggest that these mechanisms converge in a previously unsuspected way in Parkinson’s disease (Dragicevic et al., 2014).
One of the two lines of research stems from decades of work to define how the activity of midbrain dopamine neurons is controlled. These neurons alternate between a relatively slow, baseline, pacemaking activity (∼4 Hz) that presumably supplies the striatum with tonic low levels of extracellular dopamine, and bursts of activity of variable duration and only slightly higher frequency (∼15 Hz) (Grace et al., 2007). The resulting ‘bandwidth’ is not large: in contrast, activities of cortical output neurons can range from silent states to firing at frequencies of 20 Hz or more. While questions such as how salient sensory stimuli cause bursting are active areas of research, the pacemaking activity—which is autonomous, occurring even in cultured substantia nigra neurons—is fairly well elucidated, albeit subject to continuing elaboration in papers such as the one being discussed here.
In contrast to most other tonically active CNS neurons, which depend …