M1 muscarinic receptor involvement in LTP induction in CA1 synapsis of rat hippocampus

GONZÁLEZ N.,OBERHOLZER M.V.,URBANO F.,SERVENT D.,JERUSALINSKY D.,KORNISIUK E.

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-Taller de Neurociencias

To investigate the participation of M1 cholinergic muscarinic receptor in synaptic plasticity in the rat hippocampus, we recorded field excitatory postsynaptic potentials (fEPSPs) in CA1 area of hippocampal slices. Muscarinic toxin MT7 from Green mamba venom is a highly selective M1 antagonist. Long term potentiation (LTP) induced by a theta burst stimulation protocol (TBS) was blocked by both scopolamine (specific muscarinic antagonist) and pirenzepine (selective M1 and M4 antagonist). We used MT7 to elucidate M1 participation in this phenomena, to find out whether it was responsible for the observed blockade of LTP by classical muscarinic antagonists. Radioligand binding assays in rat hippocampal synaptosomal membranes were performed in order to corroborate MT7 specificity on muscarinic receptors. The toxin inhibited 3H-N-methylscopolamine (muscarinic ligand) binding with Ki = 0,70 ± 0,08 nM, with a maximal inhibition of 38 ± 5 %, and did not significantly inhibit 3H-prazosin (α-adrenergic ligand) binding. In electrophysiological assays, infusion of 10 nM MT7 on rat hippocampal slices, blocked LTP induction without significant effect on basal transmission or paired pulse facilitation. We propose that M1 receptors are necessary for the induction of LTP by TBS at CA1 synapses.