A double dissociation between serial reaction time and radial maze performance in rats subjected to 192 IgG-saporin lesions of the nucleus basalis and/or the septal region

Authors

  • O. Lehmann,

    1. LN2C, UMR 7521 CNRS/Université Louis Pasteur, 12 rue Goethe, F-67000 Strasbourg, France
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    • Present address: Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.

    • The behavioural part of this work has been presented at the E.B.B.S.-E.B.P.S. meeting, Marseille, France, September 8–12, 2001 and the FENS meeting, Paris, France, July 13–17, 2002.

  • A. J. Grottick,

    1. PRBN-B, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4058 Basel, Switzerland
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    • Present address: Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego CA 92121, USA.

  • J. -C. Cassel,

    1. LN2C, UMR 7521 CNRS/Université Louis Pasteur, 12 rue Goethe, F-67000 Strasbourg, France
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  • G. A. Higgins

    1. PRBN-B, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4058 Basel, Switzerland
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    • §

      Present address: Schering Plough Research Institute, Kenilworth, NJ 07033, USA.


: Dr Jean-Christophe Cassel, as above.
E-mail: jean-christophe.cassel@psycho-ulp.u-strasbg.fr

Abstract

The cholinergic basal forebrain has been implicated in aspects of cognitive function including memory and attention, but the precise contribution of its major components, the basalocortical and the septohippocampal systems, remains unclear. Rats were subjected to lesions of either the nucleus basalis magnocellularis (Basalis), the medial septum/vertical limb of the diagonal band of Broca (Septum), or both nuclei (Basalis + Septum), using the selective cholinotoxin 192 IgG-saporin. Cognitive performance was evaluated in tasks taxing attention (the five-choice serial reaction time task, 5-CSRTT) and spatial working memory (radial arm maze, RAM). Nucleus basalis lesions disrupted performance of the 5-CSRTT, as demonstrated by decreased choice accuracy, increased incidence of missed trials, increased latencies to respond correctly, and a disrupted pattern of response control. Combined lesions of the Basalis and Septum resulted in qualitatively similar deficits to Basalis lesions alone, although interestingly, these rats were unimpaired on measures of response speed, and showed weaker deficits on accuracy and omissions. Decreasing the attentional load by lengthening stimulus duration reversed some of the deficits in Basalis and Basalis + Septum rats, suggesting an attentional deficit rather than motivation or motor perturbations. Performance in rats with septal lesions was only affected when task difficulty was increased. In the RAM an opposing pattern of effects was observed, with Septum and Basalis + Septum rats showing dramatic impairments, and Basalis rats performing normally. Taken together, these data provide clear evidence for a functional dissociation between septohippocampal and basalocortical cholinergic systems in aspects of cognitive function.

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