CULTURED BASAL FOREBRAIN CHOLINERGIC NEURONS FROM POSTNATAL RATS SHOWBOTH OVERLAPPING AND NONOVERLAPPING RESPONSES TO THE NEUROTROPHINS

Basal forebrain cholinergic neurons respond in vitro and in vivo to ne rve growth factor (NGF) and to brain-derived neurotrophic factor (BDNF ). It is not clear to what extent the neurons that respond to these tw o factors, or to neurotrophin-3 or -4/5 (NT-3; NT-4/5) are identical o r only partially overlapping populations. We have addressed this issue in cultures of basal forebrain neurons derived from 2-week-old postna tal rats, using choline acetyltransferase (ChAT) and acetylcholinester ase (AChE) as cholinergic markers. Cholinergic neuron survival was enh anced in the presence of NGF, BDNF and NT-4/5. NT-4/5 was as effective as BDNF. NT-3 was without effect at this age, although in cultures de rived from embryonic forebrain, cholinergic differentiation was induce d by NT-3. Cotreatment with NGF and BDNF resulted in small, but consis tent, increases in the number of ChAT-positive neurons, compared with either factor alone. NT-4/5 was also found to be additive with NGF, wh ereas cotreatment with BDNF and NT-4/5 showed no additivity. NT-3 had no additive effects with any other neurotrophin on any cholinergic par ameters in postnatal cultures. Taken together, the results indicate th e existence in postnatal rat brain of a large overlapping population o f cholinergic neurons that are responsive to ligands for the neurotrop hin receptors TrkA (NGF) and TrkB (BDNF and NT-4/5), but not TrkC (NT- 3), and small distinct populations that show specificity for NGF or BD NF but not both. We hypothesize that cholinergic neurons projecting in to different regions of the hippocampus may derive trophic support fro m distinct neurotrophins.