TY - JOUR T1 - Multiple NPY Receptors Coexist in Pre- and Postsynaptic Sites: Inhibition of GABA Release in Isolated Self-Innervating SCN Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7711 LP - 7724 DO - 10.1523/JNEUROSCI.16-23-07711.1996 VL - 16 IS - 23 AU - Gong Chen AU - Anthony N. van den Pol Y1 - 1996/12/01 UR - http://www.jneurosci.org/content/16/23/7711.abstract N2 - 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. ER -