title: AMPA-induced lesions of the basal forebrain differentially affect cholinergic and non-cholinergic neurons: lesion assessment using quantitative in situ hybridization histochemistry.
abstract: 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 hybridization histochemistry. Probes complementary to the sequences of choline acetyltransferase mRNA, glutamate decarboxylase mRNA and preproenkephalin mRNA were used to assess direct lesion effects within the basal forebrain and probes for postsynaptic M-1 and M-3 muscarinic receptors 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 that expressed choline acetyltransferase mRNA than ibotenic acid-induced lesions (90 versus 60%), but significantly fewer neurons which expressed either glutamate decarboxylase or preproenkephalin mRNA (61 versus 83% reduction in glutamate decarboxylase mRNA and 56 versus 79% reduction in preproenkephalin mRNA). AMPA-induced lesions did, however, destroy a significant proportion of the neurons which expressed glutamate decarboxylase and preproenkephalin mRNA (approximately 60%). The neurons spared following AMPA-induced lesions were typically situated dorsolaterally within the dorsal pallidum, although neurons expressing glutamate decarboxylase or preproenkephalin mRNA were frequently observed within the areas of greatest cholinergic neuronal loss, i.e. the region of the nucleus basalis magnocellularis. These findings suggest that there is a population of non-cholinergic pallidal neurons which are insensitive to AMPA but not to ibotenic acid, reflecting a possibly heterogeneous distribution of NMDA and non-NMDA subtypes of glutamate receptors within the rat basal forebrain. AMPA-induced lesions of the basal forebrain were, however, without significant effect on the levels of expression of M-1 and M-3 muscarinic receptor mRNAs in the cerebral neocortex.
authors.affiliation: Department of Experimental Psychology, University of Cambridge, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Page
authors.forename: D J
authors.initials: DJ
authors.lastname: Sirinathsinghji
authors.forename: B J
authors.initials: BJ
authors.lastname: Everitt
mesh_terms: D000818:Animals; D001345:Autoradiography; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D007051:Ibotenic Acid / Q000494:pharmacology; D017403:In Situ Hybridization; D008297:Male; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid