title: Lack of effect of moderate Purkinje cell loss on working memory.
abstract: 192 immunoglobulin G-saporin (192-sap) is an immunotoxin which targets the cholinergic basal forebrain after injection into either the ventricular system or the parenchyma of the rat brain. When injected by the i.c.v. route, 192-sap kills some cerebellar Purkinje cells in addition to its more extensive killing of the cholinergic basal forebrain. Behaviorally, i.c.v. injections of 192-sap result in impaired performance in a variety of experimental paradigms of learning and memory including a working memory task in the radial maze. The current study examined the contribution, if any, of immunotoxin-induced Purkinje cell loss to impaired performance in the radial maze. To meet this aim, we used i.c.v. injection of another immunotoxin, OX7-saporin (OX7-sap), at a dose that produced Purkinje cell loss of similar extent to that produced by i.c.v. 192-sap. We then compared these OX7-sap-injected rats with 192-sap-injected rats in a radial maze working memory task. We found a working memory impairment only in the 192-sap-injected rats. These data show that moderate Purkinje cell loss alone is insufficient to impair working memory. Furthermore, the data are consistent with the idea that the working memory deficit observed in 192-sap-injected animals is likely due to lesioning of the cholinergic basal forebrain.
authors.affiliation: Laboratory of Experimental Neurology, Veterans Administration Medical Center, Nashville, TN 37212, USA. wrennc@intra.nimh.nih.gov
authors.forename: C C
authors.initials: CC
authors.lastname: Wrenn
authors.forename: R G
authors.initials: RG
authors.lastname: Wiley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002755:Choice Behavior / Q000187:drug effects; D002799:Cholinergic Fibers / Q000502:physiology; D018796:Immunoconjugates; D000922:Immunotoxins / Q000494:pharmacology; D007267:Injections; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D009699:N-Glycosyl Hydrolases; D009474:Neurons / Q000187:drug effects; D016548:Prosencephalon / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D000922:Immunotoxins; C085346:OX7-saporin; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins