The degeneration of the dopaminergic neurons located in the substantia nigra is a hallmark of Parkinson’s disease while dopaminergic neurons located in another adjacent region of the brain are not as susceptible to this degeneration.
Researchers at GIGA of the ULg have shown that the density of a particular class of ion channels on these neurons differs between these two regions. Their results were recently published in the Journal of Neuroscience.
Dopamine neurons (DA) from the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are involved in various brain functions, such as movement initiation and goal directed behavior, respectively.
Dopaminergic neurons located in the ventral midbrain continuously generate a slow endogenous pacemaker activity, the mechanism of which is still debated. It has been suggested that, in the substantia nigra pars compacta (SNc), the pacemaking relies more on Ca(2+) channels and that the density of L-type Ca(2+) channels is higher in these DA neurons than in those located in the ventral tegmental area (VTA). This might lead to a higher Ca(2+) load in SNc DA neurons and explain their higher susceptibility to degeneration. However, direct evidence for this hypothesis was lacking.
Researchers from the ULg (Vincent Seutin’s laboratory, GIGA-R) found that the L-type current and channel density are indeed higher in the somata of rat SNc DA neurons and that this current undergoes less inactivation in this region. Nonstationary fluctuation analysis measurements showed a much higher number of L-type channels in the soma of SNc DA neurons, as well as a smaller single-channel conductance, pointing to a possible different molecular identity of L-type channels in DA neurons from the two areas. A major consequence of this is that pacemaking and, even more so, bursting are associated with a larger Ca(2+) entry through L-type channels in SNc DA neurons than in their VTA counterparts.
Their results establish a molecular and functional difference between two populations of midbrain DA neurons and therefore, SNc DA neurons may be physiologically exposed to a larger stress than their neighbours from the VTA. This may contribute to their differential sensitivity to neurodegeneration.