The ability of the excitotoxin, N-methyl-d,l-aspartic acid (NMA), to destroy basal forebrain cholinergic (BFC) neurons was evaluated. NMA (100 nmol) was directly injected into the peripallidum, a region containing a proportionately large number of cortically-projecting BFC neurons. Cholineacetyltransferase (ChAT) activity 10 days later was markedly and significantly reduced (up to 62%) in the cortex ipsilateral to the lesion. NMA induced a focal lesion affecting BFC neurons without damaging axons of passage or causing lesions distant from the site of injection. ChAT immunohistochemistry (IHC) was used to directly demonstrate loss of ChAT-positive neurons from the lesion site. This loss persisted at all survival times examined, from 2 days to 7.5 months post-injection.
Bibliographical noteFunding Information:
Supported in part by NIH Grants MH37967. NS12311 and AG05681. Research Scientist Award MH38894 (J.W.O.) and a Lichtenstein grant. We thank Sandra Kalmbach and Sophia Goodman, respectively, for excellent assistance in immunohistochemical procedures and preparation of the manuscript.
- N-methyl-d,l-aspartic acid
- basal forebrain