Targeting of serotonin 1A receptors to dopaminergic neurons within the parabrachial subdivision of the ventral tegmental area in rat brain

Serotonin (5-hydroxytryptamine [5-HT]) modulates dopamine-related cognitive functions and motor activity through activation of selective receptor subt ypes including 5-HT1A. Potential targets for these 5-HT1A-mediated actions of 5-HT include mesocortical and mesolimbic dopaminergic neurons having par tially segregated distribution in the parabrachial and paranigral subdivisi ons of the ventral tegmental area (VTA), respectively. We therefore examine d the ultrastructural immunocytochemical localization of the 5-HT1A recepto r in the parabrachial (VTApb) and paranigral (VTApn) subdivisions of rat VT A, to determine 1) the functional sites for receptor activation, and 2) the cellular associations between this receptor and dopaminergic neurons ident ified by their tyrosine hydroxylase (TH) content. In each region, 5-HT1A im munoreactivity was mainly observed in somatodendritic profiles, but it was also present in small unmyelinated axons and in a few axon terminals and gl ia, suggesting a role for 5-HT1A receptors in presynaptic and glial functio ns, as well as postsynaptic neuronal activation, in VTA. In somatodendritic profiles, 5-HT1A gold particles were mainly localized to tubulovesicles pr esumed to be smooth endoplasmic reticulum. In addition, however, in distal dendrites receiving multiple inputs the receptor was targeted to selective postsynaptic junctions, or more randomly distributed on nonsynaptic portion s of the plasma membrane. Of the 5-HT1A-labeled dendrites, 64% in VTApb and 44% in VTApn contained TH. These findings suggest a reserve of cytoplasmic 5-HT1A receptors that are mobilized to functional postsynaptic sites on th e plasma membrane by afferent input to distal dendrites in the VTA. They al so indicate that 5-HT1A activation may affect a larger population of dopami nergic neurons in VTApb compared with VTApn, thus having a potentially grea ter impact on cognitive functions modulated by mesocortical dopaminergic ne urons. (C) 2001 Wiley-Liss, Inc.