K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration.
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.
Institute of Neurophysiology, Neuroscience Center, Goethe-University, Frankfurt, Germany.
Julia
J
Schiemann
Falk
F
Schlaudraff
Verena
V
Klose
Markus
M
Bingmer
Susumu
S
Seino
Peter J
PJ
Magill
Kareem A
KA
Zaghloul
Gaby
G
Schneider
Birgit
B
Liss
Jochen
J
Roeper
D000818:Animals; D000229:Dependovirus / Q000235:genetics; D059290:Dopaminergic Neurons / Q000502:physiology*; D055724:Electrophysiological Phenomena; D004777:Environment; D005106:Exploratory Behavior / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D054086:KATP Channels / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000502:physiology; D010300:Parkinson Disease / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000502:physiology; D000099161:Kcnj11 Channel
D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D000099161:Kcnj11 Channel