Changes in the sensitivity of frontal cortical neurones to acetylcholine after unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole propionic acid (AMPA): effects of basal forebrain transplants into neocortex.

Unilateral S-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) lesions of the nucleus basalis magnocellularis (nbm), which produced persistent and extensive ChAT-positive cell loss within the nbm and depletion of cortical cholinergic markers in the frontal cortex, increased both the number and sensitivity of individual frontal cortical neurones responding to iontophoretic administration of ACh. The lesion also increased the sensitivity of individual neurones to carbachol but the increase in the number of neurones responding to carbachol was transient and had returned to normal 4 weeks after lesion. The sensitivity of individual neurones to glutamate was unchanged by the lesion. The percentage of cortical neurones responding to ACh, but not the sensitivity of individual neurones was restored to the prelesion level, 6-8 weeks after cholinergic transplants to the lesioned frontal cortex; cholinergic transplants to the more distant parietal cortex were only effective after 6 months whereas noncholinergic transplants were ineffective at both time intervals. Cholinergic transplants placed in the frontal cortex 6-8 weeks or 6 months before nbm lesion offered some protection from the effects of the lesion, particularly at 6 months but were ineffective when placed into the parietal cortex. Lesion of the nbm also reduced basal firing rate of spontaneously active neurones and this was not restored by any of the transplants. The results are discussed in the light of quantitative measurements of acetylcholinesterase-positive fibre outgrowth from the transplant into the recording area, which are described in the preceding manuscript [20].