REGULATION OF TRKA AND CHAT EXPRESSION IN DEVELOPING RAT BASAL FOREBRAIN - EVIDENCE THAT BOTH EXOGENOUS AND ENDOGENOUS NGF REGULATE DIFFERENTIATION OF CHOLINERGIC NEURONS

TrkA is a receptor tyrosine kinase whose activation transduces NGF sig naling. TrkA expression has been demonstrated in NGF-responsive adult basal forebrain cholinergic neurons (BFCNs). Several lines of evidence have suggested that endogenous NGF plays a role in the development an d differentiation of these neurons. We examined TrkA expression during development. TrkA mRNA and protein were present in basal forebrain ne urons during the entire postnatal period; the distribution of neurons bearing these markers was identical to that for those containing choli ne acetyltransferase (ChAT) mRNA, suggesting that, as in the adult, Tr kA gene expression is localized to BFCNs. The expression of TrkA and C hAT followed a very similar temporal pattern, suggesting regulation by the same factor(s). We discovered that NGF administration in vivo act ivated TrkA receptors, and increased both TrkA and ChAT mRNA; converse ly, anti-NGF infusions suppressed expression of both genes. These resu lts suggest that endogenous NGF regulates expression of TrkA and ChAT. Finally, while NGF infusion increased the size of developing BFCNs, N GF antibodies inhibited the normal developmental increase. The results are evidence that endogenous NGF acts on developing BFCNs to enhance gene expression and cellular differentiation.