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The Journal of Neuroscience, September 27, 2006, 26(39):10043-10050; doi:10.1523/JNEUROSCI.1819-06.2006
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Behavioral/Systems/Cognitive
Bidirectional Dopaminergic Modulation of Excitatory Synaptic Transmission in Orexin Neurons
Christian O. Alberto, Robert B. Trask, Michelle E. Quinlan, andMichiru Hirasawa Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6
Correspondence should be addressed to Dr. Michiru Hirasawa, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's Campus, Newfoundland, Canada A1B 3V6. Email: michiru{at}mun.ca
Orexin neurons in the lateral hypothalamus (LH)/perifornical area (PFA) are known to promote food intake as well as provide excitatory influence on the dopaminergic reward pathway. Dopamine (DA), in turn, inhibits the reward pathway and food intake through its action in the LH/PFA. However, the cellular mechanism by which DA modulates orexin neurons remains largely unknown. Therefore, we examined the effect of DA on the excitatory neurotransmission to orexin neurons. Whole-cell patch-clamp recordings were performed using acute rat hypothalamic slices, and orexin neurons were identified by their electrophysiological and immunohistochemical characteristics. Pharmacologically isolated action potential-independent miniatures EPSCs (mEPSCs) were monitored. Bath application of DA induced a bidirectional effect on the excitatory synaptic transmission dose dependently. A low dose of DA (1 µM) increased mEPSC frequency, which was blocked by the D1-like receptor antagonist SCH 23390, and mimicked by the D1-like receptor agonist SKF 81297. In contrast, higher doses of DA (10–100 µM) decreased mEPSC frequency, which could be blocked with the D2-like receptor antagonist, sulpiride. Quinpirole, the D2-like receptor agonist, also reduced mEPSC frequency. None of these compounds affected the mEPSCs amplitude, suggesting the locus of action was presynaptic. Furthermore, DA (1 µM) induced an increase in the action potential firing, whereas DA (100 µM) hyperpolarized and ceased the firing of orexin neurons, indicating the effect of DA on excitatory synaptic transmission may influence the activity of the postsynaptic cell. In conclusion, our results suggest that D1- and D2-like receptors have opposing effects on the excitatory presynaptic terminals impinging onto orexin neurons.
Key words: orexin neuron; dopamine; miniature EPSC; food intake; obesity; patch clamp
Received April 28, 2006; revised Aug. 3, 2006; accepted Aug. 25, 2006.
Correspondence should be addressed to Dr. Michiru Hirasawa, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's Campus, Newfoundland, Canada A1B 3V6. Email: michiru{at}mun.ca
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