WIDESPREAD NEURONAL DEGENERATION AFTER IBOTENIC ACID LESIONING OF CHOLINERGIC NEURONS IN THE NUCLEUS BASALIS REVEALED BY INSITU HYBRIDIZATION

In efforts to test the cholinergic hypothesis for Alzheimer's disease and to create an animal model for this disease, ibotenic acid has been used to lesion cholinergic neurons in the basal forebrain. In this study we have used in situ hybridization with oligonucleotide probes specific for mRNAs encoding choline acetyltransferase and glutamic acid decarboxylase, respectively, to study the effects of such a lesion. Our results show that lesion paradigms normally used to induce neuronal degeneration in nucleus basalis by ibotenic acid not only lesion the cholinergic neurons within this nucleus, but in addition, a major fraction of gamma-aminobutyric acid (GABA) neurons in nucleus basalis, substantia innominata, globus pallidus and ventral pallidum.