The
immunotoxin 192 IgG-saporin selectively destroys basal forebrain cholinergic neurons that provide
cholinergic input to the hippocampus, entire cortical mantle, amygdala, and olfactory bulb. Perinatal immunotoxic lesions by
192 IgG-saporin induce long-lasting
cholinergic depletion mimicking a number of developmental disorders reported in humans. The perinatal injection of
192 IgG-saporin induces several brain modifications, which are observed in neocortex and hippocampus at short and long term. These
plastic changes involve both structural (alterations in brain volume, neuronal morphology, and neurogenesis) and molecular (modulations of the levels of
neurotransmitters and other
proteins related to neurodegeneration) levels. Moreover, the perinatal injection of
192 IgG-saporin may interact with the brain
plastic capacity to react to other
injuries. Perinatal
192 IgG-saporin lesions allowed investigating the role of the basal forebrain
cholinergic system in modulating behavioral functions in developing as well as adult rats. After perinatal
cholinergic depletion, rats display reduced ultrasonic vocalizations as neonates, learning and exploratory deficits as juveniles, altered discriminative abilities, impulsive and perseverative behaviors, and
memory deficits as adults. Overall, these findings underline the importance of
cholinergic system integrity for the development of specific structural and functional features.