Neonatal 192 IgG-saporin lesion of forebrain cholinergic neurons: focus on the life span?

The cholinergic immunotoxin 192 IgG-saporin can be used to effect selective, substantial and permanent lesions of basal forebrain neurons in the neonatal rat. Human neurodevelopmental disorders such as Rett and Down syndromes are characterized by early cholinergic dysfunction and cognitive impairment. Hence, the study of the neonatal 192 IgG-saporin lesioned rat should illuminate the role of cholinergic dysfunction in these human disorders. To date, we and others have failed to observe notable effects of this neonatal lesion on learning and memory, even when combined with a severe lesion of noradrenergic forebrain innervation. As well, attention seems not to be affected. However, complex problem solving (intelligence?) is compromised by the cholinergic lesion. There also appears to be reduced cortical dendritic branching indicative of synapse loss but further research is needed to characterize this. Even if the synapse loss due to neonatal cholinergic lesion is modest and thus insufficient to cause a significant neurodevelopmental dysfunction, its consequences may be devastating during old age.