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Volume 16, Number 23, Issue of December 1, 1996 pp. 7711-7724
Copyright ©1996 Society for NeuroscienceMultiple NPY Receptors Coexist in Pre- and Postsynaptic Sites: Inhibition of GABA Release in Isolated Self-Innervating SCN Neurons
Received June 20, 1996; revised Aug. 29, 1996; accepted Sept. 5, 1996.
Gong Chen and Anthony N. van den Pol Section of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520
Although NPY has been shown to influence the action of many transmitters in the brain, modulation of GABA, the primary inhibitory transmitter, has not been detected with electrophysiology. Using whole-cell patch-clamp recording, we found that NPY has a large modulatory effect on GABAergic neurons of the suprachiasmatic nucleus (SCN) that act as the circadian clock in the mammalian brain. NPY, acting at both Y1- and Y2-like receptors, reduced the frequency of spontaneous miniature inhibitory postsynaptic currents while having little effect on the postsynaptic GABA receptors, suggesting a presynaptic mechanism of NPY action. In single self-innervating neurons, application of either Y1 or Y2 agonists to the same neuron significantly inhibited the evoked autaptic GABA release. The use of single-neuron microcultures has allowed the demonstration that a single peptide, NPY, has two different receptors coded for by different genes in the same axon terminal. The Y1 and Y2 agonists also inhibited whole-cell calcium currents when applied to the same neuron, indicating a coexistence of Y1- and Y2-like receptors in the postsynaptic cell body. The self-innervating cell model we use here may be applicable generally for discriminating presynaptic versus postsynaptic actions of other neurotransmitters and neuromodulators and locating their subtype receptors.
Key words: NPY; GABA; suprachiasmatic nucleus; NPY receptor; Y1-Y5 receptors; presynaptic; postsynaptic; autapse; microculture
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