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Nat Neurosci. 2012 Sep;15(9):1272-80. doi: 10.1038/nn.3185. Epub 2012 Aug 19.

K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration.

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1
Institute of Neurophysiology, Neuroscience Center, Goethe-University, Frankfurt, Germany.

Abstract

Phasic activation of the dopamine (DA) midbrain system in response to unexpected reward or novelty is critical for adaptive behavioral strategies. This activation of DA midbrain neurons occurs via a synaptically triggered switch from low-frequency background spiking to transient high-frequency burst firing. We found that, in medial DA neurons of the substantia nigra (SN), activity of ATP-sensitive potassium (K-ATP) channels enabled NMDA-mediated bursting in vitro as well as spontaneous in vivo burst firing in anesthetized mice. Cell-selective silencing of K-ATP channel activity in medial SN DA neurons revealed that their K-ATP channel-gated burst firing was crucial for novelty-dependent exploratory behavior. We also detected a transcriptional upregulation of K-ATP channel and NMDA receptor subunits, as well as high in vivo burst firing, in surviving SN DA neurons from Parkinson's disease patients, suggesting that burst-gating K-ATP channel function in DA neurons affects phenotypes in both disease and health.

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PMID:
22902720
PMCID:
PMC4242970
DOI:
10.1038/nn.3185
[Indexed for MEDLINE]
Free PMC Article
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