title: Long-term effects of immunotoxic cholinergic lesions in the septum on acquisition of the cone-field task and noncognitive measures in rats.
abstract: In rats, nonspecific mechanical or neurotoxic lesions of the septum impair spatial memory in, e.g., Morris water- and radial-maze tasks. Unfortunately, the lack of specificity of such lesions limits inferences about the role of the cholinergic hippocampal projections in spatial cognition. We therefore tested the effects of septal lesions produced by 192 IgG-saporin in rats, which is highly selective for basal forebrain cholinergic neurons, on home cage activity, noncognitive tests (modified Irwin test, open field and forced swimming tests, and various sensorimotor tasks), and the cone-field spatial learning task. The immunotoxic lesion reduced acetylcholine (ACh) levels in the septum (-61%) and hippocampus (>-75%). Rats with lesions showed mild home-cage hyperactivity at 4 weeks postlesion, but no noncognitive deficits at 13 weeks postsurgery. In the cone-field task, rats with septal lesions made more working- and reference-memory errors than the controls, but acquisition curves were parallel in both groups. The speed of visiting cones was faster in the rats with lesions, indicative of disturbed attention or increased motivation. These data support the growing evidence that involvement of the septohippocampal cholinergic system in spatial learning and memory may have been overestimated in studies that used lesions with poor selectivity.
authors.affiliation: CNS Research, Bayer, Wuppertal, Germany. FranzJosef.vanderStaay@wur.nl
authors.forename: F Josef
authors.initials: FJ
authors.lastname: van der Staay
authors.forename: Pascale
authors.initials: P
authors.lastname: Bouger
authors.forename: Olivia
authors.initials: O
authors.lastname: Lehmann
authors.forename: Christine
authors.initials: C
authors.lastname: Lazarus
authors.forename: Brigitte
authors.initials: B
authors.lastname: Cosquer
authors.forename: Julie
authors.initials: J
authors.lastname: Koenig
authors.forename: Veronika
authors.initials: V
authors.lastname: Stump
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cassel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D000922:Immunotoxins; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009699:N-Glycosyl Hydrolases; D010320:Parvalbumins / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D020665:Septum of Brain / Q000503:physiopathology*; D013028:Space Perception / Q000187:drug effects*; D013550:Swimming
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D010320:Parvalbumins; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine