D2 Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

Activation of D2 autoreceptors on midbrain dopamine neurons has been shown previously to acutely open K+ channels to inhibit intrinsically generated pacemaker activity. Here we report that D2 autoreceptors act chronically to produce an opposite action: to increase the speed and regularity of repetit...

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Bibliographic Details
Published in:The Journal of neuroscience 2006-05, Vol.26 (19), p.5240-5247
Main Authors: Hahn, Junghyun, Kullmann, Paul H. M, Horn, John P, Levitan, Edwin S
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Adaptation, Physiological - physiology
Animals
Animals, Newborn
Autoreceptors - metabolism
Biological Clocks - physiology
Cells, Cultured
Dopamine - physiology
Long-Term Potentiation - physiology
Mesencephalon - physiology
Neuronal Plasticity - physiology
Neurons - physiology
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D2 - metabolism
Time Factors
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Summary:Activation of D2 autoreceptors on midbrain dopamine neurons has been shown previously to acutely open K+ channels to inhibit intrinsically generated pacemaker activity. Here we report that D2 autoreceptors act chronically to produce an opposite action: to increase the speed and regularity of repetitive action potential firing. Voltage-, current-, and dynamic-clamp experiments, using conventional whole-cell and perforated patch-clamp recording, with cultured rat midbrain dopamine neurons show that a change in the number of functional A-type K+ channels alters firing rate and susceptibility to irregularity produced by other channels. cAMP and protein kinase A mediate the long-term action of D2 receptors in a manner that counters the short-term effect of this signaling pathway on K+ channel gating. We conclude that D2 autoreceptors, in addition to mediating acute negative feedback, are responsible for long-term enhancement of the rate and fidelity of dopamine neuron pacemaker activity.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.4976-05.2006