NEONATAL TREATMENT WITH 192 IGG-SAPORIN PRODUCES LONG-TERM FOREBRAIN CHOLINERGIC DEFICITS AND REDUCES DENDRITIC BRANCHING AND SPINE DENSITYOF NEOCORTICAL PYRAMIDAL NEURONS

The role of basal forebrain-derived cholinergic afferents in the devel opment of neocortex was studied in postnatal rats. Newborn rat pups re ceived intraventricular injections of 192 IgG-saporin. Following survi val periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological conse quences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of similar to 7 5% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization f or glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic a xons are reduced throughout the cortical layers; this reduction is mor e marked in medial than in lateral cortical areas. The thickness of ne ocortex is reduced by similar to 10%. Retrograde labeling of layer V c ortico-collicular pyramidal cells reveals a reduction in cell body siz e and also a reduction in numbers of branches of apical dendrites. Spi ne densities on apical dendrites are reduced by similar to 20-25% in 1 92 IgG-saporin-treated cases; no change was detected in number of spin es on basal dendrites; These results indicate a developmental or maint enance role for cholinergic afferents to cerebral cortical neurons.