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D2 dopamine receptors modulate neuronal resonance in subthalamic nucleus and cortical high-voltage spindles through HCN channels.
- Source :
-
Neuropharmacology [Neuropharmacology] 2016 Jun; Vol. 105, pp. 258-269. Date of Electronic Publication: 2016 Jan 22. - Publication Year :
- 2016
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Abstract
- The high-voltage spindles (HVSs), one of the characteristic oscillations that include theta frequencies in the basal ganglia (BG)-cortical system, are involved in immobile behavior and show increasing power in Parkinson's disease (PD). Our previous results suggested that the D2 dopamine receptor might be involved in HVSs modulations in a rat model of PD. Membrane resonance is one of the cellular mechanisms of network oscillation; therefore, we investigated how dopamine modulates the theta frequency membrane resonance of neurons in the subthalamic nucleus (STN), a central pacemaker of BG, and whether such changes in STN neurons subsequently alter HVSs in the BG-cortical system. In particular, we tested whether dopamine modulates HVSs through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-dependent membrane resonance in STN neurons. We found that an antagonist of D2 receptors, but not of D1 receptors, inhibited membrane resonance and HCN currents of STN neurons through a G-protein activity in acute brain slices. Our further in vivo experiments using local injection of a D2 receptor antagonist or an HCN blocker in STNs of free-moving rats showed an increase in HVSs power and correlation in the BG-cortical system. Local injection of lamotrigine, an HCN agonist, counteracted the effect induced by the D2 antagonist. Taken together, our results revealed a potential cellular mechanism underlying HVSs activity modulation in the BG-cortical system, i.e. tuning HCN activities in STN neurons through dopamine D2 receptors. Our findings might lead to a new direction in PD treatment by providing promising new drug targets for HVSs activity modulation.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Basal Ganglia drug effects
Benzazepines pharmacology
Brain Chemistry drug effects
Cerebral Cortex drug effects
Dopamine pharmacology
Dopamine Antagonists pharmacology
Electrophysiological Phenomena drug effects
Excitatory Amino Acid Antagonists pharmacology
GTP-Binding Proteins metabolism
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels agonists
Lamotrigine
Male
Parkinson Disease, Secondary chemically induced
Parkinson Disease, Secondary pathology
Rats
Rats, Sprague-Dawley
Subthalamic Nucleus drug effects
Theta Rhythm drug effects
Triazines pharmacology
Cerebral Cortex cytology
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels drug effects
Neurons drug effects
Receptors, Dopamine D2 drug effects
Subthalamic Nucleus cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 105
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26808313
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2016.01.026