Rescue of NGF-deficient mice II: basal forebrain cholinergic projections require NGF for target innervation but not guidance.
Basal forebrain cholinergic (BFC) neurons are an important substrate of cognitive function and are hypothesized to require the presence of nerve growth factor (NGF) for survival and target innervation. NGF-deficient mice develop BFC neurons that extend projections into telencephalic targets, but the mice perish before innervation is fully established. Rescue of NGF-deficient mice by transgenic expression of NGF under the keratin promoter yields viable mice with disrupted CNS expression of NGF. In the current study, rescued NGF-deficient mice contain normal numbers of septal cholinergic neurons yet reveal severe compromise of cholinergic innervation of both cortex and hippocampus. Surprisingly, intracerebroventricular infusion of NGF into juvenile mice can induce an essentially normal pattern of cholinergic innervation of the hippocampus. These results indicate that NGF is required for induction of proper innervation by BFC neurons, but that the cellular pattern of expression of this factor is not critical for specifying the distribution of axon terminals.
Phillips
Heidi S
HS
Genentech Incorporated, 1 DNA Way, South San Francisco, CA 94080, USA. hsp@gene.com
Nishimura
Merry
M
Armanini
Mark P
MP
Chen
Karen
K
Albers
Kathryn M
KM
Davis
Brian M
BM
D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002799:Cholinergic Fibers / Q000502:physiology*; D002802:Cholinesterases / Q000378:metabolism; D004586:Electrophoresis / Q000379:methods; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007633:Keratins / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism
D010320:Parvalbumins; D007633:Keratins; D020932:Nerve Growth Factor; D002802:Cholinesterases; D000109:Acetylcholine