Somatodendritic localization of 5-HT1A and preterminal axonal localizationof 5-HT1B serotonin receptors in adult rat brain

The 5-HT1A and 5-HT1B receptors of serotonin play important roles as auto- and heteroreceptors controlling the release of serotonin itself and of othe r neurotransmitters/ modulators in the central nervous system (CNS). To det ermine the precise localization of these receptors, we examined their respe ctive cellular and subcellular distributions in the nucleus raphe dorsalis and hippocampal formation (5-HT1A) and in the globus pallidus and substanti a nigra (5-HT1B), using light and electron microscopic immunocytochemistry with specific antibodies. Both immunogold and immunoperoxidase preembedding labelings were achieved. In the nucleus raphe dorsalis, 5-HT1A immunoreact ivity was found exclusively on neuronal cell bodies and dendrites, and most ly along extrasynaptic portions of their plasma membrane. After immunogold labeling, the density of membrane-associated 5-HT1A receptors could be esti mated to be at least 30-40 times that in the cytoplasm. In the hippocampal formation, the somata as well as dendrites of pyramidal and granule cells d isplayed 5-HT1A immunoreactivity, which was also prominent on the dendritic spines of pyramidal cells. In both substantia nigra and globus pallidus, 5 -HT1B receptors were preferentially associated with the membrane of fine, u nmyelinated, preterminal axons, and were not found on axon terminals. A sel ective localization to the cytoplasm of endothelial cells of microvessels w as also observed. Because the 5-HT1A receptors are somatodendritic, they ar e ideally situated to mediate serotonin effects on neuronal firing, both as auto- and as heteroreceptors. The localization of 5-HT1B receptors to the membrane of preterminal axons suggests that they control transmitter releas e from nonserotonin as well as serotonin neurons by mediating serotonin eff ects on axonal conduction. The fact that these two receptor subtypes predom inate at extrasynaptic and nonsynaptic sites provides further evidence for diffuse serotonin transmission in the CNS. J. Comp. Neurol. 417:181-194, 20 00. (C) 2000 Wiley-Liss, Inc.