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 cells were compared using intracellular recording in the presence of glutamatergic 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 hyperpolarized a proportion of type I hilar neurons (60%) and decreased their input resistance through activation of a K+-conductance. This effect was mediated by serotonin(1A) receptors since it was mimicked by the selective serotonin(1A) receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide and blocked by the selective serotonin(1A) receptor antagonist (+) WAY 100135. In some type I hilar neurons (40%) neither serotonin nor (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide induced a membrane hyperpolarization. Instead, serotonin induced an excitatory response, depolarizing the cells and blocking the slow afterhyperpolarization. Similar effects were seen in all hilar neurons after blockade of serotonin(1A) receptors. They were mimicked by the serotonin(4) receptor agonist zacopride. Serotonin induced either decreases or increases in the frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic potentials in granule cells via activation of serotonin(1A) and of serotonin(4) receptors, respectively. 4-aminopyridine-evoked GABA(B) receptor-mediated inhibitory postsynaptic potentials were inhibited by serotonin via activation of serotonin(1A) receptors. 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 proportion of inhibitory neurons in the dentate area does not express serotonin(1A) receptors and is excited by serotonin. Other inhibitory neurons express serotonin(1A) receptors and are inhibited by serotonin. (C) 1997 IBRO. Published by Elsevier Science Ltd.