Behavioural Brain Research 213 (2010) 304–312 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory Vootele Voikar a,∗ , Giovanni Colacicco a , Oliver Gruber a , Elisabetta Vannoni a , Hans-Peter Lipp a,b , David P. Wolfer a,c,d a Institute of Anatomy, University of Zurich, Switzerland b NewBehavior AG, Zurich, Switzerland c Institute for Human Movement Sciences, ETH Zurich, Switzerland d Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland article info Article history: Received 13 April 2010 Received in revised form 9 May 2010 Accepted 12 May 2010 Available online 21 May 2010 Keywords: IntelliCage Home cage Mice Inbred strain Avoidance Learning Memory Hippocampus Striatum Lesion abstract The IntelliCage allows fully automated continuous testing of various behaviours in the home cage envi- ronment without handling the mice. Here we tested whether conditioned avoidance is retained after a time period delay spent outside the IntelliCage. During the training, nosepokes in one of the four learning corners were punished with an air-puff. After 24 h of training, the mice were placed in regular cages for 24 h. During the last 18 h of this interval, the mice were water deprived and then returned to the IntelliCage for a probe trial where drinking was allowed in all corners. The C57BL/6 mice developed a significant suppression of nosepoking in the punished corner during training, and the avoidance was carried over to the following probe trial. Repetition of the experiment by delivering punishment in a dif- ferent corner assigned to individual mice revealed a similar performance pattern. Comparison between the different strains revealed a reduced nosepoke suppression in DBA/2 and B6D2F1 mice as compared to C57BL/6 mice in the probe trial, despite similar error rates during the training with short (1-s) air-puffs. However, the performance of the three strains in the probe trial were equalised when the air-puffs were prolonged until the end of the corner visit. Significant extinction of the nosepoke suppression occurred after 6 days. A prolonged interval (7 days) between the training and the probe trial resulted in a loss of suppression in DBA/2 mice, but not in C57BL/6 and B6D2F1 mice. Additional experiments revealed that performance in the probe trial was dependent on a complex set of intramaze cues. Testing of mice with bilateral excitotoxic lesions of the hippocampus or dorso-lateral striatum revealed that learning this task was dependent on an intact hippocampus, but not on an intact striatum. In summary, the condi- tioned nosepoke suppression test presented here is sensitive to both genetic differences and hippocampal lesions. This test could be applied to the screening of mutant mice with impaired hippocampal functions more efficiently than those of the standard memory tests. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Behavioural phenotyping of mice has received a great deal of attention during the past 15 years. The main reason for the increased interest is the explosion in the number of transgenic mouse models and there are several projects whose goal is to identify the functions for every single gene [10]. Thus, behavioural studies with mutant mice are of crucial importance [6,56]. More- ∗ Corresponding author. Institute of Anatomy, University of Zurich, Winterthur- erstrasse 190, CH-8057 Zurich, Switzerland. Tel.: +41 4463 55359; fax: +41 4463 55702. E-mail address: vootele.voikar@gmail.com (V. Voikar). over, conflicting results between laboratories investigating the same strains of mice are not uncommon. Therefore, the scientific community is looking for improvements in the reproducibility of experiments [11,60]. A number of behavioural tests and models for mice are available [13]. However, the intensive application of these tests has identified several problems and drawbacks. The most important questions regarding the validity of these tests include the effect of handling by the experimenter, the individual housing of the animals and the extensive time required to run a conventional battery of tests [9,45,50,57–59]. In order to overcome some of these problems, novel systems have been developed that allow the continuous monitoring of mouse behaviour in their home cage and also allow the detection 0166-4328/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2010.05.019