D2 Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity

• 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
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4976-05.2006

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.