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Comparing tonic and phasic calcium in the dendrites of vulnerable midbrain neurons
  • Rita Yu-Tzu Chen,
  • Rebekah Evans
Rita Yu-Tzu Chen
Georgetown University Medical Center
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Rebekah Evans
Georgetown University Medical Center

Corresponding Author:[email protected]

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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.
28 Aug 2023Submitted to European Journal of Neuroscience
29 Aug 2023Assigned to Editor
29 Aug 2023Submission Checks Completed
30 Aug 2023Review(s) Completed, Editorial Evaluation Pending
31 Aug 2023Reviewer(s) Assigned
13 Sep 2023Editorial Decision: Revise Major