Aminergic receptors during the development of the human brain: the contribution of in vitro imaging techniques

The development of the human brain is a complex process and, in this regard, the maturation of neurotransmitter systems and their receptors is of special interest. The study of these systems requires methodological approaches with powerful anatomical resolution. In this paper we review the application of visualization procedures to the fine localization, pattern of appearance and functional relevance of monoaminergic receptors in postmortem human brain samples corresponding to different stages of development (fetal, neonatal, infant). Data obtained by using mostly in vitro autoradiography but also in situ hybridization and, very recently, second messenger labeling, are discussed, including the methodological limitations inherent in working with inmature human tissue. From these studies, several conclusions were made. (1) It is possible to visualize, in the human brain with high resolution, the presence of neuroreceptors at early prenatal stages. (2) The anatomical distribution of monoaminergic receptors in the developing human brain is, in general terms, comparable to that found in the adult. (3) During the developmental process, some receptors, which are early and sometimes transiently expressed, play important thophic roles in the regulation of neuronal development: this is the case with the serotonin 5-HT1A receptors, which attain peak levels of hyperexpression over the hippocampus (dentate gyrus, dendritic areas of CA fields) and the raphe nuclei and show a transient expression in the cerebellum, around the 25 week of gestational age. (4) Different patterns of ontogenetic appearance for human receptors have been identified: dopamine D2-like (caudate, putamen, nigra) and 5-HT1A receptors are good examples of prenatal development, while 5-HT1B sites (basal ganglia, neocortex) present a mainly postnatal pattern of appearance. (5) Neurotransmitter receptors at human fetal stages are already functional from the point of view of transducing response.