Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in thedevelopment of neocortex was studied in postnatal rats. Newborn rat pupsreceived intraventricular injections of 192 IgG-saporin. Following survivalperiods ranging from 2 days to 6 months, the brains were processed todocument the cholinergic lesion and to examine morphological consequences.Immunocytochemistry for choline acetyltransferase (ChAT) and in situhybridization for ChAT mRNA demonstrate a loss of approximately 75% of thecholinergic neurons in the medial septum and nucleus of the diagonal bandof Broca in the basal forebrain. In situ hybridization for glutamic aciddecarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons.Acetylcholinesterase histochemistry demonstrates a marked reduction of thecholinergic axons in neocortex. Cholinergic axons are reduced throughoutthe cortical layers; this reduction is more marked in medial than inlateral cortical areas. The thickness of neocortex is reduced byapproximately 10%. Retrograde labeling of layer V cortico-collicularpyramidal cells reveals a reduction in cell body size and also a reductionin numbers of branches of apical dendrites. Spine densities on apicaldendrites are reduced by approximately 20-25% in 192 IgG- saporin-treatedcases; no change was detected in number of spines on basal dendrites. Theseresults indicate a developmental or maintenance role for cholinergicafferents to cerebral cortical neurons.