Unilateral Hippocampal Blockade Reveals That One Hippocampus Is Sufficient for Learning a Passive Avoidance Task J.M. Cimadevilla, 1 M. Mendez, 2 M. Mendez-Lopez, 2 and J.L. Arias 2 * 1 Department of Neuroscience, University of Almeria, Almeria, Spain 2 Department of Psychology, University of Oviedo, Oviedo, Spain Understanding hippocampal participation in memory processes is one of the goals in neuroscience research. By blocking the hippocampus unilaterally in Wistar rats, we assessed the contribution of this brain structure to memory in a passive avoidance task. Subjects were distributed into four groups. Group 1 received tetrodo- toxin (TTX) in the right hippocampus during acquisition and retrieval phases. Group 2 had the same procedure as group 1, except that the contralateral hippocampus was blocked during retrieval. Subjects from group 3 acquired the task with saline (both hippocampi intact) and retrieved with the right hippocampus inactivated. Finally, group 4 received TTX unilaterally 2 min after ac- quisition to determine the hippocampal role in consoli- dation. Results showed that group 2 was impaired, compared with the other groups, during retrieval. These findings reveal that the hippocampal contribution to this task differs from that in other tasks considered to be hippocampus dependent. V V C 2007 Wiley-Liss, Inc. Key words: rat; memory; behavior Since the mid-1950s, the hippocampal formation has attracted the attention of hundreds of neuroscientists in the attempt to understand the neurobiological basis of memory (Scoville and Milner, 1957). Now, nobody questions the hippocampal contribution to many forms of memory, including spatial memories (O’Keefe and Dostrovsky, 1971; Morris et al., 1982) and contextual and inhibitory avoidance (Lorenzini et al., 1996; Stubley- Weatherly et al., 1996; Izquierdo et al., 2002; Burwell et al., 2004). Considerable effort has been expended to under- standing how the different hippocampal areas and regions participate in memory functions (Fenton and Bures, 1993; Hock and Bunsey, 1998; Moser and Moser, 1998; Kesner et al., 2004; Cimadevilla et al., 2005). It is well known that subjects can master hippocampus- dependent tasks, such as the Morris water maze (MWM), with a small part of the hippocampal volume, irrespec- tive of whether the intact tissue is located unilaterally or bilaterally (Moser et al., 1993; Moser and Moser, 1998; De Hoz et al., 2005). Nevertheless, the same hippocam- pal intervention can produce different behavioral effects according to the demands of the task. Hence, unilateral blockade of the dorsal hippocampus does not prevent learning in the MWM but does impair acquisition in an active place avoidance task (Fenton and Bures, 1993; Cimadevilla et al., 2001). The passive avoidance task has been used in many learning and memory studies, because it requires very little specialist training. This hippocampus-dependent task requires the subjects learning to inhibit their natural tend- ency to cross from a lit chamber to a nonilluminated com- partment. Because training requirements are restricted in time, this task provides an adequate way to evaluate differ- ent questions regarding the contribution of one hippocam- pus to memory. By using reversible blockade methods, this study will determine whether one hippocampus is enough to acquire, consolidate, and retrieve memories in a passive avoidance task and how these memories are organized in both hippocampi. MATERIALS AND METHODS Animals We used 40 3-month-old male Wistar rats (275–350 g) from the breeding colony of the University of Oviedo (Spain). Subjects were housed in pairs on a 12-hr light-dark cycle with food and water available ad libitum and a constant temperature of 20–218C. The study was carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC) for the care and use of laboratory animals. Surgery Subjects were anesthetized with ketamine (50 mg/kg i.p.) and xilazynum (20 mg/kg i.m.). By using a Kopf Contract grant sponsor: MEC, Spain; Contract grant number: SEJ2004- 07445; Contract grant number: SEJ2005-05067. *Correspondence to: Dr. Jorge Luis Arias Perez, Department of Psychol- ogy, University of Oviedo, Plaza de Feijoo s/n, 33003 Oviedo, Spain. E-mail: jarias@uniovi.es Received 18 October 2006; Revised 22 November 2006; Accepted 1 December 2006 Published online 4 March 2007 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/jnr.21222 Journal of Neuroscience Research 85:1138–1142 (2007) ' 2007 Wiley-Liss, Inc.