Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells

被引:398
作者
Aghajanian, GK
Marek, GJ
机构
[1] YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06508
[2] CONNECTICUT MENTAL HLTH CTR,NEW HAVEN,CT 06508
关键词
EPSCs; 5-HT2A receptor; glutamatergic terminals; prefrontal cortex; metabotropic glutamate receptor; tetrodotoxin; 5-HT;
D O I
10.1016/S0028-3908(97)00051-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
By intracellular and whole cell recording in rat brain slices, it was found that bath-applied serotonin (5-HT) produces an increase in the frequency and amplitude of spontaneous excitatory postsynaptic potentials/currents (EPSPs/EPSCs) in layer V pyramidal cells of neocortex and transitional cortex (e.g. medial prefrontal, cingulate and frontoparietal). The EPSCs were suppressed by LY293558, an antagonist selective for the AMPA subtype of excitatory amino acid receptor, and by two selective 5-HT2A receptor antagonists, MDL 100907 and SR 46349B. In addition, the EPSCs were suppressed by the fast sodium channel blocker tetrodotoxin (TTX) and were dependent upon external calcium. However, despite being TTX-sensitive and calcium dependent, there was no evidence that the EPSPs resulted from an increase in impulse flow in excitatory neuronal afferents to layer V pyramidal cells. The EPSCs could be induced rapidly by the microiontophoresis of 5-HT directly to ''hot spots'' within the apical (but not basilar) dendritic field of recorded neurons, indicating that excitatory amino acids may be released by a TTX-sensitive focal action of 5-HT on a subset of glutamatergic terminals in this region. Consistent with such a presynaptic action, the inhibitory metabotropic glutamate receptor agonist (1S,3S)-aminocyclopentane-1,3-dicarboxylate markedly reduced the induction of EPSPs by 5-HT. Postsynaptically, 5-HT enhanced a subthreshold TTX-sensitive sodium current, potentially contributing to an amplification of EPSC amplitudes. These data suggest 5-HT, via 5-HT2A receptors, enhances spontaneous EPSPs/EPSCs in neocortical layer V pyramidal cells through a TTX-sensitive focal action in the apical dendritic field which may involve both pre- and postsynaptic mechanisms. (C) 1997 Elsevier Science Ltd.
引用
收藏
页码:589 / 599
页数:11
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