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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.

Original publication

DOI

10.1038/nn.3185

Type

Journal article

Journal

Nat Neurosci

Publication Date

09/2012

Volume

15

Pages

1272 - 1280

Keywords

Animals, Dependovirus, Dopaminergic Neurons, Electrophysiological Phenomena, Environment, Exploratory Behavior, Gene Silencing, Humans, Immunohistochemistry, KATP Channels, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Confocal, Motor Activity, Parkinson Disease, Patch-Clamp Techniques, Potassium Channels, Inwardly Rectifying, RNA, Messenger, Receptors, N-Methyl-D-Aspartate, Substantia Nigra, Ventral Tegmental Area