Comparing tonic and phasic calcium in the dendrites of vulnerable
midbrain neurons
Abstract
Several midbrain nuclei degenerate in Parkinson’s Disease. Many of these
nuclei share the common characteristics that are thought to contribute
to their selective vulnerability, including pacemaking activity and high
levels of calcium influx. In addition to the well-characterized
dopaminergic neurons of the substantia nigra pars compacta (SNc), the
cholinergic neurons of the pedunculopontine nucleus (PPN) also
degenerate in PD. It is well established that the low-threshold L-type
calcium current is a main contributor to tonic calcium in SNc
dopaminergic neurons and is hypothesized to contribute to their
selective vulnerability. However, it is not yet clear whether the
vulnerable PPN cholinergic neurons share this property. Therefore, we
used two-photon dendritic calcium imaging and whole-cell
electrophysiology to evaluate the role of L-type calcium channels in the
tonic and phasic activity of PPN neurons and the corresponding dendritic
calcium signal and directly compare these characteristics to SNc
neurons. We found that blocking L-type channels reduces tonic firing
rate and dendritic calcium levels in SNc neurons. By contrast, the
calcium load in PPN neurons during pacemaking did not depend on L-type
channels. However, we find that blocking L-type channels reduces phasic
calcium influx in PPN dendrites. Together, these findings show that
L-type calcium channels play different roles in the activity of SNc and
PPN neurons, and suggest that low-threshold L-type channels are not
responsible for tonic calcium levels in PPN cholinergic neurons and are
therefore not likely to be a source of selective vulnerability in these
cells.