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 spec ial interest. The study of these systems requires methodological approaches with powerful anatomical resolution. In this paper we review the applicati on of visualization procedures to the fine localization, pattern of appeara nce and functional relevance of monoaminergic receptors in postmortem human brain samples corresponding to different stages of development (fetal, neo natal, infant). Data obtained by using mostly in vitro autoradiography but also in situ hybridization and, very recently, second messenger labeling. a re discussed, including the methodological limitations inherent in working with inmature human tissue. From these studies, several conclusions were ma de. (1) It is possible to visualize, in the human brain with high resolutio n, the presence of neuroreceptors at early prenatal stages. (2) The anatomi cal distribution of monoaminergic receptors in the developing human brain i s, in general terms, comparable to that found in the adult. (3) During the developmental process, some receptors, which are early and sometimes transi ently expressed, play important thophic roles in the regulation of neuronal development: this is the case with the serotonin 5-HT1A receptors, which a ttain peak levels of hyperexpression over the hippocampus (dentate gyrus, d endritic areas of CA fields) and the raphe nuclei and show a transient expr ession in the cerebellum, around the 25 week of gestational age. (4) Differ ent patterns of ontogenetic appearance for human receptors have been identi fied: dopamine D-like (caudate, putamen, nigra) and 5-HT1A receptors are go od examples of prenatal development, while 5-HT1B sites (basal ganglia, neo cortex) present a mainly postnatal pattern of appearance. (5) Neurotransmit ter receptors at human fetal stages are already functional from the point o f view of transducing response. (C) 2001 Elsevier Science B.V. All rights r eserved.