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A developmental role of the cholinergic basal forebrain: behavioural and neurochemical effects of neonatal 192 IgG-saporin lesions.

Ricceri L, Calamandrei G, Berger-Sweeney J (1999) A developmental role of the cholinergic basal forebrain: behavioural and neurochemical effects of neonatal 192 IgG-saporin lesions. Neuroscience 1999 Abstracts 559.6. Society for Neuroscience, Miami, FL.

Summary: Cholinergic basal forebrain (BF) fibers begin to innervate neocortex and hippocampus during the first week of life in rodents. Because this is a dynamic period in cortical synaptogenesis and organization, we have hypothesized that the cholinergic BF provides its targets with critical signals that influence cortical organization and cognitive behavioral later in life. Neocortical projection fibers reportedly innervate their targets early in the first postnatal week, whereas hippocampal projections innervate their targets later in the first postnatal week. Previously we have shown that intraventricular injections of the selective cholinergic immunotoxin 192 IgG saporin on postnatal day (pnd) 7 impair passive avoidance (PA) acquisition, but not retention, on pnd 15-16 and significantly reduce hippocampal (78%) and neocortical (64%) choline acetyltransferase (ChAT) activity. In the present study, we attempted to produce significant reductions in cholinergic activity earlier in development, when primarily neocortical projections are developing, and assess effects on neurochemistry and behavior. Wistar rats received intraventricular injections of 192 IgG saporin on pnd 1 and 3. PA acquisition and retention were assessed on pnd 15-16. Lesioned rats acquired the PA task slower than control littermates, whereas 24-hr retention was not affected. On pnd 20, ChAT activity in neocortex and hippocampus was assessed. There was a 63% reduction in neocortical and 45 % reduction in hippocampal ChAT activity. These data suggest that interrupting cholinergic input to neocortex and hippocampus early in the first week of life affects cognitive behaviors. Interestingly, this early lesion also leads to abnormalities in cortical cytoarchitecture that strongly resemble those occurring in developmental disorders associated with mental retardation (Robertson et al. 1998). Supported by ISS intramural fundings,NSF IBN9458101 and Whitehall Foundation.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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