Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that modulates
N-methyl-D-aspartate (NMDA) receptor activity by binding to several different 5-HT receptor subtypes.
In the present study, we used whole-cell patch-clamp recordings in transverse slice preparations
to test the role of 5-HT receptors in modulating the NMDA receptor-mediated miniature excitatory
postsynaptic currents (mEPSCs) in layer II/III pyramidal neurons of the rat visual cortex. We
found that the NMDA receptor-mediated component of mEPSCs could be potentiated by exogenously
applied 5-HT. Similar results were obtained by exogenously applied 5-CT or 8-OH-DPAT
(the 5-HT1A and 5-HT7 receptor agonist). A specific antagonist for the 5-HT7 receptor, SB-269970,
completely blocked the increase in NMDA receptor-mediated component of mEPSCs by 5-CT or 8-
OH-DPAT. Moreover, the selective 5-HT1A receptor antagonist, WAY-100135, displayed no influence
on the enhancement in NMDA receptor-mediated component of mEPSCs by 5-CT or 8-OHDPAT.
These results indicated that the increase in NMDA receptor-mediated component of mEPSCs
by 5-HT in layer II/III pyramidal neurons of the young rat visual cortex requires activation of 5-HT7
receptors, but not 5-HT1A receptors. These observations might be clinically relevant to schizophrenia
and Alzheimer's disease (AD), where enhancing NMDA receptor-mediated neurotransmission is
considered to be a promising strategy for treatment of these diseases.
Keywords: Serotonin, 5-HT7 receptor, NMDA receptor, mEPSCs, visual cortex.
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