The Journal of Neurophysiology Vol. 80 No. 3 September 1998, pp. 1116-1121
Copyright ©1998 The American Physiological Society

Serotonin Reduces Polysynaptic Inhibition via 5-HT_1A Receptors in the Superficial Entorhinal Cortex

Dietmar Schmitz¹, Tengis Gloveli¹, Ruth M. Empson², and Uwe Heinemann¹

¹ Department of Neurophysiology, Institute of Physiology at the Charité, Humboldt University Berlin, 10117 Berlin, Germany; and ² University Department of Pharmacology, Oxford University, Oxford OX1 3QT, United Kingdom

Schmitz, Dietmar, Tengis Gloveli, Ruth M. Empson, and Uwe Heinemann. Serotonin reduces polysynaptic inhibition via 5-HT_1A receptors in the superficial entorhinal cortex. J. Neurophysiol. 80: 1116-1121, 1998. The superficial cells of the entorhinal cortex (EC), main input to the hippocampus, receive a serotonergic input from the raphe nuclei and express 5-hydroxytryptamine creatine sulfate complex (5-HT) receptors at high density. With the use of intracellular recordings, we investigated the effects of serotonin on synaptic inhibition of layer II and III neurons of the EC. Serotonin reduced both polysynaptic fast and slow inhibitory postsynaptic potentials (IPSPs) in projection neurons of the superficial EC. Polysynaptic fast and slow IPSPs were depressed by serotonin in a dose-dependent manner (0.1-100 µM). Serotonin in a concentration of 1 µM reduced the amplitudes of polysynaptic fast and slow IPSPs by ~40 and 50%, respectively. To identify the subtype of the 5-HT-receptor mediating the effects on polysynaptic IPSPs, we applied various 5-HT-receptor agonists and antagonists. Although the serotonin agonists for the 5-HT_1B,2C,3 receptors were ineffective, the effects were mimicked by the 5-HT_1A-receptor agonists (8-OH-DPAT, 5-CT) and prevented by the 5-HT_1A-receptor antagonist NAN-190. To look at the direct effects of 5-HT on inhibitory interneurons, we elicited monosynaptic IPSPs in the absence of excitatory synaptic transmisson. In contrast to the polysynaptic IPSPs, monosynaptic IPSPs were not significantly affected by serotonin. Recordings from putative inhibitory interneurons revealed that their excitatory postsynaptic potentials (EPSPs) were reversibly reduced by serotonin. We conclude that serotonin suppresses polysynaptic inhibition in projection neurons of layers II and III of the EC by depression of EPSPs on inhibitory interneurons via 5-HT_1A receptors.

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