K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration
| Autor: | Markus Bingmer, Kareem A. Zaghloul, Julia Schiemann, Birgit Liss, Susumu Seino, Gaby Schneider, Jochen Roeper, Falk Schlaudraff, Peter J. Magill, Verena Klose |
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| Rok vydání: | 2012 |
| Předmět: |
Patch-Clamp Techniques
Substantia nigra Environment Motor Activity Biology Receptors N-Methyl-D-Aspartate Article Midbrain Mice Bursting KATP Channels Dopamine medicine Animals Humans Gene Silencing RNA Messenger Patch clamp Potassium Channels Inwardly Rectifying Mice Knockout Microscopy Confocal Dopaminergic Neurons General Neuroscience Ventral Tegmental Area Parkinson Disease Dependovirus Immunohistochemistry Potassium channel Electrophysiological Phenomena Mice Inbred C57BL Substantia Nigra Ventral tegmental area medicine.anatomical_structure nervous system Exploratory Behavior NMDA receptor Neuroscience medicine.drug |
| Zdroj: | Nature Neuroscience. |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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