Expression of tyrosine hydroxylase in neurons of cultured cerebral cortex: evidence for phenotypic plasticity in neurons of the CNS.

In vivo, neurons of the cerebral cortex of rat embryos did not stain with antibodies to the catecholamine (CA) biosynthetic enzyme tyrosine hydroxylase (TH) even when examined using a highly sensitive technique for radioimmunocytochemistry. However, when embryonic day (E) 13 cortex was grown 1 d in culture, several thousand cells expressed immunoreactive and catalytically active TH. All TH cells simultaneously labeled with the neuronal enzyme, neuronal specific enolase, indicating that the TH was exclusively localized in neurons. Moreover, all TH neurons were postmitotic since they did not incorporate 3H-thymidine. With time in culture, the number of TH cells selectively declined from nearly 3000 cells at 2 d to several cells at 14 d. Similarly, the number of neurons competent to express TH in culture declined with advancing age of the donor embryo. Thus, by E18, very few cortical neurons had the capacity to express TH. We conclude that during a critical period of development, postmitotic cerebral cortical neurons can express catecholamine traits in vitro but not in vivo. Thus, the neurotransmitter phenotype of certain classes of central neurons is not fixed but can be influenced by epigenetic factors found in their environment, thereby providing evidence of phenotypic plasticity in the central nervous system (CNS).