Ontogeny of 5-HT1A receptor expression in the developing hippocampus

Serotonin (5-HT) has long been implicated in a number of neurodevelopmental processes including neuronal cell division, migration, neurite outgrowth, and synapse formation. However, relatively little is known about how these effects are mediated during normal brain development in vivo and the identity of the receptor subtypes involved in mediating these effects. In recent years, a number of pharmacological studies have suggested a role for the serotonin 1A (5HT1A) receptor subtype in mediating the developmental effects of 5-HT in the hippocampus. These studies, however, have been difficult to interpret due to lack of information regarding the expression and distribution of 5HT1A in the developing brain and hippocampus in particular. In the current study, specific anti-5-HT1A antibodies, developed in our laboratory [F.C. Zhou, T.D. Patel, D. Swartz, Y. Xu, M.R. Kelley, Production and characterization of an anti-serotonin 1A receptor antibody which detects functional 5-HT1A binding sites, Brain Res Mol Brain Res, 69 (1999) 186-201], were utilized to map the ontogeny and distribution of the 5HT1A receptor protein in the developing rat hippocampus through embryonic and early postnatal life. This is the first such study of 5-HT1A expression in the developing rat brain. Our findings revealed that expression of the 5HT1A receptor emerges during the initial stages of embryonic hippocampal development. Remarkably, most if not all hippocampal neurons begin to express 5HT1A shortly upon completion of their terminal mitosis. We found that 5HT1A is initially concentrated around the cell bodies and later becomes more sparsely distributed along the dendrites after the neurons have matured. In addition to postmitotic neurons, we have observed that S100 and GFAP positive glia transiently express 5HT1A during early postnatal development of the hippocampus. These findings demonstrate that the 5-HT1A receptor is positioned to mediate developmental effects of serotonin in the hippocampus. Furthermore, the temporal patterns of expression suggest a role for 5-HT1A in postmitotic events such as neuronal migration, neurite outgrowth, and phenotypic differentiation.