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K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration
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K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration
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Journal Article
K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration
2012
Overview
The authors show that K-ATP channels in dopamine (DA) neurons of the medial substantia nigra (m-SN) enable burst firing
in vitro
and
in vivo
. Silencing K-ATP channel activity in m-SN DA neurons decreases novelty-dependent exploratory behavior in mice.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Behavior
/ Biomedical and Life Sciences
/ Dopamine
/ Dopaminergic Neurons - physiology
/ Electrophysiological Phenomena
/ Exploratory Behavior - physiology
/ Humans
/ KATP Channels - biosynthesis
/ Mice
/ Neurons
/ Parkinson Disease - physiopathology
/ Potassium Channels, Inwardly Rectifying - genetics
/ Receptors, N-Methyl-D-Aspartate - biosynthesis
/ Receptors, N-Methyl-D-Aspartate - genetics
/ RNA, Messenger - biosynthesis
