Neuropeptide Y-2 receptors inhibit the frequency of spontaneous but not miniature EPSCs in CA3 pyramidal cells of rat hippocampus

1. Neuropeptide Y (NPY) inhibits synaptic excitation in hippocampal area CA3. We studied its site of action with the use of whole cell patch-clamp recordings from CA3 pyramidal cells of rat hippocampal slices in vitro. 2. Spontaneous excitatory postsynaptic currents (sEPSCs) were isolated with picrotoxin, to block gamma-aminobutyric acid-A receptors, whereas miniature excitatory postsynaptic currents (mEPSCs) were isolated by additionally treating the slice with tetrodotoxin (TTX) and/or Cd2+. sEPSCs and mEPSCs were eliminated by the excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M) and DL-2-amino-5-phosphonovaleric acid (50 mu M), and were thus solely attributable to glutamate release. 3. The interval and amplitude distributions of sEPSCS and (TTX-isolated) mEPSCS were analyzed. Either NPY or the rapidly reversible, Y-2-receptor-selective agonist [6-aminohexanoic(5-24)] NPY, ([ahx(5-24)]NPY) sharply increased the inter-sEPSC intervals in 16 of 16 neurons tested. In 11 of these cells, these agonists also simultaneously shifted the sEPSC amplitude distribution to somewhat smaller amplitudes, whereas in the remaining 5 cells, no concurrent effect on amplitudes was observed. By contrast, in 15 separate neurons treated with 1 mu M TTX, neither NPY nor [ahx(5-24)]NPY altered either mEPSC amplitude or interval distributions of the mEPSCs. 4. To directly compare the effects of Y-2 receptor activation on sEPSC and mEPSC properties, we applied [ahx(5-24)]Npy to the same cell in the absence and presence of TTX (n = 7). sEPSC intervals were characteristically increased by the Y-2 agonist in all cells; in six of seven cells the sEPSC distribution was also shifted to smaller amplitudes. TTX application reduced the mean amplitude of the synaptic events more than did [ahx(5-24)]NPY, while increasing their intervals. [ahx(5-24)]NPY had no effect in TTX. 5. NPY, acting on a Y-2 receptor, inhibits impulse-dependent synaptic excitation of CA3 pyramidal cells of the rat hippocampus by an entirely presynaptic action.