Muscarinic Cholinergic Neurotransmission in CA1 synapses of rat hippocampus

OBERHOLZER MV, CERVEÑANSKY C, URBANO F, KORNISIUK E, JERUSALINSKY DA

BEXCO, Busan, Korea

Congreso; The 22nd Biennal Meeting of the International Society for Neurochemistry/APSN; 2009

International Society for Neurochemistry

Muscarinic antagonists produce amnesia while agonists facilitate memory when injected into the dorsal hippocampus of rats immediately after training in an inhibitory avoidance task. Muscarinic toxin MT2 from Green Mamba venom acts as selective M1 agonist and M4 antagonist, improving performance in an inhibitory avoidance task. MT3 from the same venom, a highly selective M4 antagonist, inhibited long-term potentiation (LTP) induced by high frequency stimulation, in field potential and in whole-cell configuration recordings of CA1 synapses in rat hippocampal slices. Our goal was to characterize the participation of muscarinic receptors in those synapses, either in basal conditions or after potentiation by theta-burst stimulation (TBS). Field excitatory postsynaptic potentials (fEPSP) were obtained by stimulating Schaffer Collaterals and recording at glutamatergic synapses on pyramidal cell dendrites in the presence of scopolamine, atropine (specific non-selective muscarinic antagonists), pirenzepine (selective antagonist for M1 and M4 receptors) and MT2. fEPSP maximum slopes were analysed and compared to control recordings. Both scopolamine and pirenzepine 25uM blocked LTP induction, while atropine 10uM did not. None of them affected basal transmission in the concentrations used. On the other hand, 1uM MT2 showed a facilitatory –though no lasting- effect (+50 ± 7%), which was blocked by pirenzepine. This facilitation by MT2 was not blocked with scopolamine, but was suppressed by atropine. Altogether, our results show that both M1 and M4 appear positively involved in LTP induction by TBS, while only M1 receptors appear to positively modulate basal transmission in CA1 synapses.