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The entorhinal cortex is a gateway to the hippocampus; it receives inputs from several cortical associative areas as well as subcortical areas. Since there is evidence showing that noradrenaline reduces the epileptic activity generated in the entorhinal cortex, we have examined the action of noradrenaline in the superficial layer of the entorhinal cortex, which is the main source of afferents to the hippocampus. In a previous study we showed that noradrenaline hyperpolarized layer II entorhinal cortex neurons and reduced global synaptic transmission via alpha 2-adrenoreceptors. Here we present a detailed analysis of the effect of noradrenaline on membrane resistance and on the pharmacologically isolated postsynaptic potentials in layer II entorhinal cortex neurons of mice. Noradrenaline (50 microM) hyperpolarized most layer II entorhinal cortex neurons. This hyperpolarization corresponded to an outward current with a reversal potential following the Nernst equilibrium potential for potassium. The hyperpolarizing effect of noradrenaline was blocked by 10 microM yohimbine. These observations suggest that noradrenaline activates a potassium conductance via an alpha 2-adrenoreceptor. Noradrenaline (10-50 microM) reversibly reduced the amplitude of the pharmacologically isolated excitatory potentials mediated by both NMDA and alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors, the former being more strongly affected. Again this effect was blocked by 10 microM yohimbine. In contrast, GABAA-mediated synaptic transmission was virtually unaffected by noradrenaline. Thus, noradrenaline appears to strongly inhibit the glutamate-mediated synaptic transmission in the entorhinal cortex without affecting inhibitory post-synaptic potentials. These observations suggest that alpha 2-adrenergic receptor agonists may exert a beneficial effect in the control of hyperexcitability in temporal lobe epilepsy.
Carl Petersen, Sylvain Crochet, Célia Roxane Gasselin, Benoît Hohl
Matthias Wolf, Henry Markram, Felix Schürmann, Eilif Benjamin Muller, Srikanth Ramaswamy, Michael Reimann, Daniel Keller, Werner Alfons Hilda Van Geit, James Gonzalo King, Pramod Shivaji Kumbhar, Alexis Arnaudon, Jean-Denis Georges Emile Courcol, Rajnish Ranjan, Armando Romani, András Ecker, Michael Emiel Gevaert, Vishal Sood, Sirio Bolaños Puchet, James Bryden Isbister, Judit Planas Carbonell, Daniela Egas Santander, Maria Reva, Genrich Ivaska, Natali Barros Zulaica, Mustafa Anil Tuncel, Christoph Pokorny, Elvis Boci, Jorge Blanco Alonso, Aleksandra Zuzanna Teska, Darshan Mandge, Polina Litvak, Gianluca Ficarelli, Weina Ji, Giuseppe Chindemi, Christian Andreas Rössert, Omar Awile, Joni Henrikki Herttuainen, Samuel Lieven D. Lapere, Thomas Brice Delemontex, Tanguy Pierre Louis Damart, Alexander Dietz