p11 is an adaptor protein which binds to serotonin 5-HT(1B) receptors and 5-HT(4) receptors and regulates their localization at the cell surface. In the present study, we examined to what extent p11 containing neurons co-expressed 5-HT(1B)R and/or 5-HT(4)R in cerebral cortex, hippocampus, cerebellum and caudate-putamen. A triple-labeling immunohistochemical approach was taken using antibodies to detect native p11 and 5-HT(1B)R combined with visualization of EGFP driven under the 5-HT(4)R promoter in BAC-transgenic mice. In the caudate-putamen, the hippocampal pyramidal cell layer of CA1 and the hippocampal granule cell layer of dentate gyrus, most p11 containing cells co-expressed both 5-HT(1B)R and 5-HT(4)R. In the cingulate cortex, stratum radiatum/oriens of CA1, hilus of the dentate gyrus and cerebellar cortex, many cells co-expressed p11 and 5-HT(1B)R, but not 5-HT(4)R. In the studied brain regions, few cells solely expressed p11 without any significant expression of 5-HT(1B)R or 5-HT(4)R. It can be concluded that p11 is anatomically positioned to modulate serotonin neurotransmission, via 5-HT(1B)R and 5-HT(4)R, in brain regions important for emotionality, cognition and locomotion.
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