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Volume 17, Number 20, Issue of October 15, 1997 pp. 7872-7880
Copyright ©1997 Society for Neuroscience

Serotonin Promotes the Differentiation of Glutamate Neurons in Organotypic Slice Cultures of the Developing Cerebral Cortex

Received June 25, 1997; revised August 4, 1997; accepted August 5, 1997.

Alexandros A. Lavdas1, Mary E. Blue2, Jill Lincoln1, and John G. Parnavelas1

1 Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom, and 2 Kennedy Krieger Research Institute and Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The monoamines serotonin (5-HT), noradrenaline (NA), and dopamine (DA), which are present in the developing brain apparently before they assume their neurotransmitter functions, are regarded as strong candidates for a role in the maturation of the cerebral cortex. Here we sought to investigate their effects on the generation and differentiation of cortical cell types. Slice cultures, prepared from the cortices of embryonic day (E) 14, E16, and E19 rat fetuses, were kept in defined medium or in defined medium plus 5-HT for 7 d. E16 cortices were also exposed to NA or DA for the same period. At the end of this period, the proportions of the neuronal [glutamate (Glu)-, GABA-, calbindin-, calretinin-labeled], glial (GFAP), and neuroepithelial (nestin) cell types were estimated for all conditions. We found that in E16 cultures, application of 5-HT, but not of NA or DA, significantly increased the proportion of Glu-containing neurons without affecting the overall neuronal population or the proportions of any other cell types. A similar effect was observed in co-cultures of E16 cortex with slices through the midbrain raphe nuclei of E19 rats. The total amount of cortical Glu, as measured with HPLC, was also increased in these co-cultures. To investigate whether the effect of 5-HT was the result of changes in cell proliferation, we exposed slices to bromodeoxyuridine (BrdU) and found that the proportion of BrdU-labeled cells was similar in the 5-HT-treated and control slices. These results indicate that 5-HT promotes the differentiation of cortical Glu-containing neurons without affecting neuroepithelial cell proliferation.

Key words: neocortex; development; monoamines; 5-HT; neurons; glutamate; BrdU; slice cultures




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