Studies suggest that cholinergic neurons of the medial septum directly or indirectly modulate GABAergic and glutamatergic neurotransmission in the hippocampus. The intent of this study was to determine the effect of selective lesion of cholinergic neurons in the medial septum on the extracellular fluid concentrations of acetylcholine, GABA and glutamate and the maximal binding of muscarinic, GABAA
and NMDA receptors in the hippocampus. The results showed that 6 weeks following intraseptal injection of the selective immunotoxin 192 IgG-saporin there was an 87% decrease in choline acetyltransferase activity, a 77% decrease in basal acetylcholine concentration and a greater than 3 fold increase in muscarinic receptor binding in the hippocampus. There were no significant changes in either the concentrations of GABA or glutamate or in maximal binding of GABAA
or NMDA receptors. These results suggest that over time the hippocampus can compensate for a substantial loss of cholinergic tone and maintain GABAergic and glutamatergic neurotransmission. This, in turn, may mitigate the degree of functional deficit associated with cholinergic hypofunction of the medial septum and may provide an explanation for why selective cholinergic lesions reportedly have less effect on working memory performance than originally anticipated.
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