Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners, and shelter. It results from two very different strategies: (1) place learning which enables for flexible way finding and (2) response learning that leads to a more rigid “route following.” Despite the importance of knockout techniques that are only available in mice, little is known about mice' flexibility in spatial navigation tasks. Here we demonstrate for C57BL6/N mice in a water-cross maze (WCM) that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid (IA) disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits. In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice.
Keywords: spatial memory, cognitive flexibility, response learning, place learning, hippocampus, MRI volumetry, ibotenic acid
Citation: Kleinknecht KR, Bedenk BT, Kaltwasser SF, Grünecker B, Yen Y-C, Czisch M and Wotjak CT (2012) Hippocampus-dependent place learning enables spatial flexibility in C57BL6/N mice. Front. Behav. Neurosci. 6:87. doi: 10.3389/fnbeh.2012.00087
Received: 15 October 2012; Paper pending published: 23 October 2012;
Accepted: 23 November 2012; Published online: 27 December 2012.
Edited by:Melly S. Oitzl, Leiden University Medical Center, Netherlands
Reviewed by:Howard Eichenbaum, Boston University, USA
Copyright © 2012 Kleinknecht, Bedenk, Kaltwasser, Grünecker, Yen, Czisch and Wotjak. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Carsten T. Wotjak, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany. e-mail: firstname.lastname@example.org
†These authors equally contributed to this work and share the first authorship.