Enlarged cholinergic forebrain neurons and improved spatial learning in p75 knockout mice

The p75 low affinity neurotrophin receptor (p75) can induce apoptosis in va rious neuronal and glial cell types. Because p75 is expressed in the cholin ergic neurons of the basal forebrain, p75 knockout mice may be expected to show an increased number of neurons in this region. Previous studies, howev er, have produced conflicting results, suggesting that genetic background a nd choice of control mice are critical. To try to clarify the conflicting r esults from previous reports, we undertook a further study of the basal for ebrain in p75 knockout mice, paying particular attention to the use of gene tically valid controls. The genetic backgrounds of p75 knockout and control mice used in this study were identical at 95% of loci. There was a small d ecrease in the number of cholinergic basal forebrain neurons in p75 knockou t mice at four months of age compared with controls. This difference was no longer apparent at 15 months due to a reduction in numbers in control mice between the ages of 4 and 15 months. Cholinergic cell size in the basal fo rebrain was markedly increased in p75 knockout mice compared with controls. Spatial learning performance was consistently better in p75 knockout mice than in controls, and did not show any deterioration with age. The results indicate that p75 exerts a negative influence on the size of cholinergic fo rebrain neurons, but little effect on neuronal numbers. The markedly better spatial learning suggests that the function, as well as the size, of choli nergic neurons is negatively modulated by p75.