DIFFERENTIAL EXPRESSION OF IMMEDIATE-EARLY GENES IN DISTINCT LAYERS OF RAT CEREBRAL-CORTEX AFTER SELECTIVE IMMUNOLESION OF THE FOREBRAIN CHOLINERGIC SYSTEM

The aim of this study was to show whether reduction or loss of cortica l cholinergic activity results in any particular change in the express ion of the proto-oncogenes c-fos and/or c-jun. To produce cortical cho linergic hypofunction, the monoclonal antibody, 192IgG, to the low-aff inity nerve growth factor receptor p75(NGFR) coupled to a cytotoxin, s aporin, was used as an efficient and selective immunotoxin for choline rgic neurons in rat basal forebrain. Brain sections of adult rats that had received an intracerebroventricular injection of 4 mu g of the 19 2IgG-saporin were subjected to in situ hybridization using oligonucleo tides to detect c-fos and c-jun mRNA. Autoradiographs obtained were ev aluated by quantitative image analysis. Seven days following injection of the immunotoxin there was a dramatic loss in acetylcholinesterase staining in frontal, parietal, piriform, temporal, and occipital corti ces, hippocampus, and olfactory bulb, but not in the striatum and cere bellum. In situ hybridization revealed a considerable increase in the level of c-fos mRNA in the lateral septum following the cholinergic le sion, whereas in the medial septum both c-fos and c-jun mRNA were elev ated. Immunolesioning led to a distinct and specific increase in the l evel of c-jun but not c-fos mRNA in the parietal and occipital cortex that was restricted to cortical layer IV. These data suggest that redu ced cortical cholinergic activity differentially regulates expression of c-fos/c-jun genes in distinct cortical regions of the rat brain. (C ) 1994 Wiley-Liss, Inc.