CELLULAR-DISTRIBUTION OF NICOTINIC ACETYLCHOLINE-RECEPTOR SUBUNIT MESSENGER-RNAS IN THE HUMAN CEREBRAL-CORTEX AS REVEALED BY NONISOTOPIC IN-SITU HYBRIDIZATION

The pharmacology of telencephalic nicotinic acetylcholine receptors (nAChRs) has become an important issue in recent years. While in the human brain a direct pharmacological assessment is difficult to achieve the visualization of nAChRs has been enabled by histochemical techniques providing an ever increasing and improving resolution. Receptor autoradiography was used to visualize binding sites on the level of cortical layers whereas immunohistochemistry has allowed for the cell type-specific and ultrastructural localization of receptor protein. Further investigations have to elucidate the cellular sites of nAChR biosynthesis by visualizing subunit-specific transcripts. Using autopsy samples of the human precentral cortex (Area 4) as a paradigm we have applied digoxigenin-labeled cRNA probes to localize transcripts for the alpha 3- and alpha 4-1-subunits of the nAChR. In accordance with findings in the monkey cortex, the alpha 3-subunit seems to be expressed mainly in pyramidal neurons of layers III-VI of the human cerebral cortex. Transcripts for the alpha 4-1-subunit, by contrast, appear to be present in a large number of neurons throughout all layers of the cerebral cortex, consonant with its ubiquitous distribution in the rodent brain. The present findings show that also in human autopsy brains the cell type-specific detection of nAChR transcripts is possible. For the future, this technique will enable to investigate the expression of receptor transcripts in diseased human brains as compared to controls.