Expression of trkB and trkC mRNAs by adult midbrain dopamine neurons: A double-label in situ hybridization study

The documented trophic actions of the neurotrophins brain-derived neurotrop hic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5) upo n ventral mesencephalic dopamine neurons in vitro and in vivo are presumed to be mediated through interactions with their high-affinity receptors TrkB (for BDNF and NT-4/5) and TrkC (for NT-3). Although both neurotrophin rece ptor mRNAs have been detected within the rat ventral midbrain, their specif ic association with mesencephalic dopaminergic cell bodies remains to be el ucidated. The present study was performed to determine the precise organiza tion of trkB and trkC mRNAs within rat ventral midbrain and to discern whet her the neurotrophin receptor mRNAs are expressed specifically by dopaminer gic neurons. In situ hybridization with isotopically labeled cRNA probes sh owed that trkB and trkC mRNAs were expressed in all mesencephalic dopamine cell groups, including all subdivisions of the substantia nigra and ventral tegmental area, and in the retrorubral held, rostral and caudal linear rap he nuclei, interfascicular nucleus, and supramammillary region. Combined is otopic/nonisotopic double-labeling in situ hybridization demonstrated that virtually all of the tyrosine hydroxylase (the catecholamine biosynthetic e nzyme) mRNA-containing neurons in the ventral midbrain also expressed trkB or trkC mRNAs. Additional perikarya within these regions expressed the neur otrophin receptor mRNAs but were not dopaminergic. The present results demo nstrate that essentially all mesencephalic dopaminergic neurons synthesize the neurotrophin receptors TrkB and TrkC and thus exhibit the capacity to r espond directly to BDNF and NT-3 in the adult midbrain in vivo. Moreover, b ecause BDNF and NT-S are produced locally by subpopulations of the dopamine rgic cells, the present data support the notion that the neurotrophins can influence the dopaminergic neurons through autocrine or paracrine mechanism s. J. Comp. Neurol. 403:295-308, 1999. (C) 1999 Wiley-Liss, Inc.