Altered processing of novel information in N-CAM-de¢cient mice M. Montag-Sallaz, 1,2,CA D. Montag 1,2 and M. Schachner 1,3 1 Department of Neurobiology, Swiss Federal Institute of Technology (ETH), Hoenggerberg, CH- 8093 Zurich, Switzerland; 2 Neurogenetics Research Group, Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg; 3 Zentrum fˇr Molekulare Neurobiologie, UniversitÌt Hamburg, Martinistr. 52, D-20246 Hamburg, Germany CA,2 Corresponding Author and Address: sallaz@ifn-magdeburg.de DOI: 10.1097/01.wnr.0000077549.91466.4c N-CAM-de¢cient mice display anatomical and electrophysiological abnormalities in the CNS and behavioral de¢cits. Here, we address the question whether information processing is altered in these mice by analysis of the expression of c- fos and arg 3.1/arc in N- CAM-de¢cient mice after presentation of saccharin as novel or fam- iliar and water as neutral gustatory stimulus. When compared to their wild-type control littermates, increased expression of c- fos mRNA in the amygdala after the novel taste and of arg 3.1/arc mRNA in the dentate gyrus 4.5 h after the neutral taste was de- tected in the absence of N-CAM. Furthermore, the novelty-in- duced increase in arg 3.1/arc expression in the cingulate cortex 4.5 h after the novel taste was not observed in N-CAM-de¢cient mice. These data suggest that information processing mediated by immediate-early gene expression is altered in N-CAM-de¢cient mice. NeuroReport 14 :1343^1346  c 2003 Lippincott Williams & Wilkins. Key words: Arg 3.1/arc; Brain diseases; Immediate early genes; Information processing; Learning and memory; c- fos; N-CAM; N-CAM-de¢cient mice; Schizophrenia INTRODUCTION The neural cell recognition molecule N-CAM is a widely expressed cell surface glycoprotein of the immunoglobulin superfamily involved in neuronal migration and connectiv- ity, axonal growth and fasciculation [1]. Several lines of evidence have demonstrated clearly a crucial role of N- CAM in neuronal plasticity underlying stabilization of memory [2,3]. The pathways by which recognition mol- ecules may influence memory formation, induction and maintenance of LTP, and formation of new synapses could involve modulation of second messenger cascades and/or possibly activation of IEG expression [4]. Mice deficient for all isoforms of the N-CAM protein exhibit two major anatomical abnormalities: a size reduction of the olfactory bulb resulting from an altered cell migration process [5], and strong alterations in mossy fiber growth and fasciculation [6]. Lately, long-term but not short-term plasticity at mossy fiber synapses has been shown to be impaired in N-CAM-deficient mice [7]. N-CAM null mutant mice display an impairment in exploratory behavior and learning abilities in the Morris water maze [5]. In addition, these mice show increased intermale aggression [8], abnormal anxiety-like behavior and higher response to 5- HT 1A receptor stimulation [9]. However, processing of information, and particularly of novel vs familiar, in N- CAM-deficient mice has not been analyzed. To address this, we studied the expression of the proto-oncogene c-fos, one of the best characterized modulator genes [10], and of the effector immediate-early gene activity-regulated gene 3.1 (arg 3.1 [11]; activity-regulated cytoskeleton-associated protein, arc [12]) in the brain of mice deficient in N-CAM after presentation of a familiar, a novel or a neutral gustatory stimulus. In a previous study, we showed that expression of c-fos 0.5 h and of arg 3.1/arc 0.5 h and 4.5 h after presentation of a novel gustatory stimulus is increased in particular brain structures, but not after presentation of the same stimulus when familiar [13]. Our results show in N-CAM-deficient mice compared to wild-type control littermates increased expression of c-fos mRNA in the amygdala mainly after presentation of the novel taste, and of arg 3.1/arc mRNA in the dentate gyrus 4.5 h after drinking water as neutral taste. In addition, in the cingulate cortex, 4.5 h after the novel taste, expression of arg 3.1/arc mRNA was reduced in mutant versus wild-type mice and the novelty-induced increase in arg 3.1/arc expression was not detectable in the mutants, suggesting that processing of novel information may be altered in N-CAM-deficient mice. MATERIALS AND METHODS Animals: N-CAM-deficient (N-CAM/) mice back- crossed to strain C57BL/6 mice have been described previously [5]. Two to three-month-old male and female N-CAM/ and wild-type littermate mice (N-CAM + / + ) were raised from a heterozygous (N-CAM + /) breeding stock in our animal facility and individually housed under 0959- 4965  c Lippincott Williams & Wilkins Vol 14 No 10 18 July 2003 1343 CLINICAL NEUROSCIENCE NEUROREPORT Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.