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Journal of Neuroscience, Vol 15, 7217-7225, Copyright © 1995 by Society for Neuroscience
Serotonin reduces inhibition via 5-HT1A receptors in area CA1 of rat hippocampal slices in vitro
D Schmitz, RM Empson and U Heinemann
Institute for Physiology at the Charite, Department of Neurophysiology, Humboldt University Berlin, Germany.
We studied the effects of serotonin (5-HT) on intrinsic and synaptic
responses of hippocampal CA1 cells. The effects were partially mimicked by
the 5-HT1A receptor agonist, 8-OH-DPAT, and prevented by the 5-HT1A
receptor antagonist, NAN-190. Polysynaptic fast and slow inhibitory
postsynaptic potentials (IPSPs) were reduced in amplitude by 60-70%
following application of both 5-HT and 8-OH-DPAT. Monosynaptic fast IPSPs
were reduced by 60% and slow IPSPs by 90% following application of both
drugs. Since there is a temporal overlap of fast and slow IPSPs, the
reduction in fast IPSPs could have arisen indirectly from the larger effect
of 5-HT on slow IPSPs. To overcome this problem we blocked the slow IPSPs
with new, potent GABA-B antagonists, but still observed a similar reduction
in the fast IPSP with 5-HT and 8-OH-DPAT. However, the reductions in the
fast IPSPs could also have arisen from the 5-HT-induced total conductance
increases. Using single-electrode voltage clamp and intracellular K+
channel blockers we still observed similar changes. 5-HT and 8-OH-DPAT had
no effect upon GABA-A-mediated currents evoked by iontophoretic GABA
application to the dendrites or the soma of CA1 pyramidal cells, Putative
inhibitory internuerons were hyperpolarized by 5-HT and their evoked EPSPs
strongly reduced by 5-HT and 8-OH-DPAT. Our data indicate that 5-HT
modulates fast and slow synaptic inhibition of principal cells using
presynaptic mechanisms involving the inhibition of inhibitory interneurons.
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