Enhanced learning in mice parallels vector-mediated nerve growth factor expression in hippocampus

Spatial learning requires the integrity of the nerve growth factor (NGF)-re sponsive septohippocampal pathway. Loss of a single NGF allele at the mouse NGF locus (heterozygous null, ngf(+/-)) reduces septohippocampal NGF level s and NGF-regulated cholinergic neurotransmitter enzymes and results in spa tial learning deficits in adult animals. A herpes simplex virus (HSV) ampli con vector was utilized to locally deliver NGF to the hippocampus of mice h eterozygous and wild type (ngf(+/+)) at the NGF gene locus. NGF gene transf er produced transient increases in NGF protein levels and choline acetyltra nsferase activity in both ngf(+/-) and ngf(+/+) mice. However, spatial lear ning capability was improved only in ngf(+/-) mice. In aggregate, these fin dings suggest that amplicon-directed expression of NGF in subjects with bas eline septohippocampal dysfunction can correct spatial learning deficits.