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T-type calcium channels trigger a hyperpolarization induced afterdepolarization in vulnerable subpopulation of substantia nigra dopamine neurons

Friday, September 18, 2015 — Poster Session V

2:00 p.m. – 3:30 p.m.
FAES Terrace

* FARE Award Winner


  • RC Evans
  • ZM Khaliq


Substantia nigra pars compacta (SNc) dopamine neurons are essential for initiating movement. The degeneration of these neurons is the hallmark of Parkinson’s Disease, and damage to these neurons in animal models causes Parkinson’s like symptoms. One prominent hypothesis is that calcium through voltage gated calcium channels causes or exacerbates SNc degeneration. Most work on this calcium toxicity hypothesis implicates the L-type calcium channel. However, we have recently found that under hyperpolarized conditions, the T-type calcium channel can trigger a large after-depolarization and a corresponding influx of calcium into dopamine neuron dendrites. Specifically we have used computational modeling, electrophysiology, and two-photon calcium imaging in mouse midbrain slices to show that this hyperpolarization-induced afterdepolarization (HI-ADP) depends on T-type, but not L-type calcium channels. Interestingly, not all dopamine neurons displayed this HI-ADP. Other studies have shown that there are subpopulations within the SNc that differentially degenerate in Parkinson’s Disease. During disease progression, the ventral SNc neurons appear to be more vulnerable while the dorsal SNc neurons are relatively resilient. We stained cells for calbindin, a marker for the resilient SNc cells, in slices previously used for electrophysiology. In this way we could compare the resilient and vulnerable populations. We found that the HI-ADP was much stronger in the vulnerable, calbindin-negative neurons than in the resilient neurons. These results suggest that the T-type calcium channel characteristics may differ between these populations. Because these channels can cause large calcium transients they may contribute to the vulnerability of specific SNc dopamine neurons in Parkinson’s Disease.

Category: Neuroscience