AMPA-INDUCED LESIONS OF THE BASAL FOREBRAIN DIFFERENTIALLY AFFECT CHOLINERGIC AND NONCHOLINERGIC NEURONS - LESION ASSESSMENT USING QUANTITATIVE IN-SITU HYBRIDIZATION HISTOCHEMISTRY

The direct and transynaptic effects of lesions of the basal forebrain induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ( AMPA) and ibotenic acid were investigated using quantitative in situ h ybridization histochemistry. Probes complementary to the sequences of choline acetyltransferase mRNA, glutamate decarboxylase mRNA and prepr oenkephalin mRNA were used to assess direct lesion effects within the basal forebrain and probes for postsynaptic M-1 and M-3 muscarinic rec eptors were used to assess long-term changes in neocortical muscarinic receptor mRNA expression following cholinergic deafferentation, AMPA- induced basal forebrain lesions destroyed significantly more neurons t hat expressed choline acetyltransferase mRNA than ibotenic acid-induce d lesions (90 versus 60%), but significantly fewer neurons which expre ssed either glutamate decarboxylase or preproenkephalin mRNA (61 versu s 83% reduction in glutamate decarboxylase mRNA and 56 versus 79% redu ction in preproenkephalin mRNA). AMPA-induced lesions did, however, de stroy a significant proportion of the neurons which expressed glutamat e decarboxylase and preproenkephalin mRNA (similar to 60%). The neuron s spared following AMPA-induced lesions were typically situated dorsol aterally within the dorsal pallidum, although neurons expressing gluta mate decarboxylase or preproenkephalin mRNA were frequently observed w ithin the areas of greatest cholinergic neuronal loss, i.e. the region of the nucleus basalis magnocellularis. These findings suggest that t here is a population of noncholinergic pallidal neurons which are inse nsitive to AMPA but not to ibotenic acid, reflecting a possibly hetero geneous distribution of NMDA and non-NMDA subtypes of glutamate recept ors within the rat basal forebrain, AMPA-induced lesions of the basal forebrain were, however, without significant effect on the levels of e xpression of M-1 and M-3 muscarinic receptor mRNAs in the cerebral neo cortex.