Muscarinic M1 modulation on basal neurotransmission in CA1 region of rat hippocampus

OBERHOLZER MV ; KORNISIUK E; URBANO FJ; SERVENT D; CERVENANSKY C; JERUSALINSKY D

Huerta Grande, Cordoba, Argentina.

Congreso; IIRCN- Second Joint Meeting of the Argentine Society for Neuroscience (SAN: XXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias) and the Argentine Workshop in Neuroscience (TAN: XII Taller Argentino de Neurociencias); 2010

SAN-TAN

To investigate the putative M1 muscarinic receptor modulation in CA1 synapses of rat hippocampus, we used muscarinic toxins (MTs) from Green Mamba venom as selective M1 receptor ligands. MT1 and MT2 are M1 agonists and M4 antagonists. MT7 is a highly selective M1 antagonist. We have shown that MT2 enhanced field potentials (fEPSP) in CA1 region of rat hippocampus and this was blocked by both pirenzepine and atropine. We performed 3H-N-methylscopolamine (3H-NMS) and 3H-prazosin (3H-PRZ) binding assays in hippocampal synaptosomal membranes to evaluate MTs specificities. All toxins inhibited 3H-NMS binding with Ki=89}10 nM for MT1; 3,2}0,9 ƒÊM for MT2 and 0,70}0,08 nM for MT7. MT1 and MT2 inhibited 3H-PRZ binding with Ki=83}3 nM and 292}11 nM. MT7 did not inhibit 3H-PRZ binding. Perfusion of 1ƒÊM MT1 enhanced fEPSP by 45}4 %; this facilitation was blocked by 10nM MT7. Perfusion of 10ƒÊM PRZ enhanced basal fEPSP in 16}3 %. Blockade of MT2Ls effect by both pirenzepine and atropine and MT1Ls blockade by MT7 evidence M1 involvement in these effects. Since PRZ inhibited 3H-NMS binding (Ki = 5,1}1,2 ƒÊM), we speculate that PRZ effect on fEPSP could be mediated by muscarinic receptors. These results show that M1 receptors positively modulate basal transmission in CA1 synapses.