EFFECTS OF SEROTONIN THROUGH SEROTONIN(1A), AND SEROTONIN(4) RECEPTORS ON INHIBITION IN THE GUINEA-PIG DENTATE GYRUS IN-VITRO

The role of serotonin(1A) and serotonin(4) receptors in the modulation of synaptic inhibition in the dentate gyrus of guinea-pig hippocampal slices was studied. The effects of serotonin (5-hydroxytryptamine) on hilar neurons and on inhibitory postsynaptic potentials in granule ce lls were compared using intracellular recording in the presence of glu tamatergic receptor antagonists. On the basis of electrophysiological properties hilar neurons were classified as type I neurons (presumably inhibitory) and type IT neurons (presumably excitatory). Serotonin hy perpolarized a proportion of type I hilar neurons (60%) and decreased their input resistance through activation of a K+-conductance. This ef fect was mediated by serotonin(1A) receptors since it was mimicked by the selective serotonin(1A) receptor agonist (+/-)-8-hydroxy-dipropyla minotetralin hydrobromide and blocked by the selective serotonin(1A) r eceptor antagonist (+) WAY 100135. In some type I hilar neurons (40%) neither serotonin nor (+/-)-8-hydroxy-dipropylaminotetralin hydrobromi de induced a membrane hyperpolarization. Instead, serotonin induced an excitatory response, depolarizing the cells and blocking the slow aft erhyperpolarization. Similar effects were seen in all hilar neurons af ter blockade of serotonin(1A) receptors. They were mimicked by the ser otonin(4) receptor agonist zacopride. Serotonin induced either decreas es or increases in the frequency of spontaneous GABA(A) receptor-media ted inhibitory postsynaptic potentials in granule cells via activation of serotonin(1A) and of serotonin(4) receptors, respectively. 4-amino pyridine-evoked GABA(B) receptor-mediated inhibitory postsynaptic pote ntials were inhibited by serotonin via activation of serotonin(1A) rec eptors. However, after blockade of serotonin(1A) receptors, serotonin increased the frequency of GABA(B)-inhibitory postsynaptic potentials through the activation of serotonin(4) receptors. We conclude that a p roportion of inhibitory neurons in the dentate area does not express s erotonin(1A) receptors and is excited by serotonin. Other inhibitory n eurons express serotonin(1A) receptors and are inhibited by serotonin. (C) 1997 IBRO. Published by Elsevier Science Ltd.