Ž . Brain Research 834 1999 136–141 www.elsevier.comrlocaterbres Short communication Differential effects of 192IgG-saporin and NMDA-induced lesions into the basal forebrain on cholinergic activity and taste aversion memory formation Humberto Gutierrez, Ranier Gutierrez, Ricardo Silva-Gandarias, Jimena Estrada, Marıa Isabel Miranda, ´ ´ ´ Federico Bermudez-Rattoni ) ´ Instituto de Fisiologıa Celular, UniÕersidad Nacional Autonoma de Mexico, Apartado Postal 70-253, 04510, Mexico, D.F., Mexico ´ ´ ´ Accepted 20 April 1999 Abstract Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of Ž . cortical acetylcholine activity. In this study, we have performed a detailed analysis of the cholinergic status of the insular cortex IC Ž . Ž . following local injections of either 192IgG-saporin 192IgG-sap or N-methyl-D-aspartate NMDA directly into the nucleus basalis Ž . magnocellularis NBM . By means of in vivo microdialysis, we show that the immunotoxin lesion results in an almost complete lack of extracellular acetylcholine release, whereas NMDA-induced lesions result in a marginal reduction in cortical cholinergic activity. Choline–acetyltransferase activity in the IC further confirmed this differential pattern of cortical deafferentation. Surprisingly, however, only NMDA-induced lesions showed a strong disruptive effect upon taste aversion learning whereas no detectable deficits could be found following 192IgG-sap lesions. By combining intrabasal injections of 192IgG-sap with acute pre-training infusions of the cholinergic antagonist scopolamine into the IC, a strong disruption of taste aversion was attained. These results imply that residual cholinergic activity, following 192IgG-saporin lesions, might be still critical for normal cortical mediation of memory processing. They also support the role of basal forebrain in mediating learning and memory processes, and demonstrate that mnemonic deficits resulting from excitotoxic lesions of the basal forebrain are not the sole result of cortical acetylcholine activity hypofunction. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Acetylcholine; ChAT; Microdialysis; Muscarinic antagonist; NBM The cholinergic basal forebrain complex provides widespread, topologically organised afferent cholinergic innervation to many brain regions including the whole wx cortical mantle, hippocampus and amygdala 7 . A great number of studies have implicated the involvement of basal forebrain cholinergic neurons in the mediation of learning and memory processes in experimental animals w x 11–13,17,24 . Learning deficits associated with lesions of Ž . nucleus basalis magnocellularis NBM produced by injec- tions of excitatory amino acid agonists have been demon- w x strated in a great variety of tasks 24,27 . Mnemonic deficits associated to these lesions have been classically attributed to the resulting depletion of cortical acetyl- choline activity. Nevertheless, many researchers have re- ported that the magnitude of decrease in cortical choline ) Corresponding author. Fax: q 525-622-5607; E-mail: fbermude@ifcsun1.ifisiol.unam.mx Ž . acetyltransferase ChAT following excitotoxic lesions of the NBM is unrelated to the degree of cognitive impair- w x ment 4,10,21 . Ž . Recently, depletion of the nerve growth factor NGF receptor-bearing cholinergic neurons in the rat basal fore- brain, with a corresponding selective loss of cholinergic innervation in the related cortical regions has been ob- tained following intracerebral injections of a newly intro- w x duced immunotoxin, 192IgG-saporin 8,30 . Investigations carried out using this highly efficient immunotoxin have repeatedly failed to reproduce the kind of memory deficits normally found as a result of the less selective excitotoxic lesions, thus questioning the concept of a direct role for Ž . cortical acetylcholine ACh input in memory formation w x 3,5,25,26,28,29 . Here, we use a well-known cortically mediated learning paradigm, conditioned taste aversion Ž . CTA , in order to directly address the issue of whether the ascending cholinergic input is critically involved in the cortex mediation of memory formation. The CTA is a very robust and widely used model for the study of learning and 0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 01519-X