Short Communication Reversible Changes in Hippocampal CA1 Synapses Associated With Water Maze Training in Rats RUBE ´ N MIRANDA, 1 * EDUARDO BLANCO, 1 AZUCENA BEGEGA, 1 LUIS J. SANTI ´ N, 2 AND JORGE L. ARIAS 1 1 Laboratory of Psychobiology, School of Psychology, University of Oviedo, Spain 2 Psychobiology Area, School of Psychology, University of Ma ´ laga, Spain KEY WORDS stratum radiatum CA1; hippocampus; spatial learning; synapses; electron microscopy ABSTRACT Long-term memories seem to require protein synthesis to be estab- lished. This process can be related with synaptogenesis resulting in changes in the form or even in the number or proportion of synaptic contacts. Results from behavioral stud- ies assessing quantitative changes associated with different learning tasks are contro- versial. The aim of our work was to assess whether the number of CA1 hippocampal syn- aptic contacts can be modified after training in different tasks in the Morris water maze (MWM). We found transient changes in the synaptic density of the symmetric synapses associated with place learning. A reduced synaptic density of the symmetric synapses in the stratum radiatum of CA1 was found at 48 h posttraining, returning to control levels 72 h posttraining. The same effect was observed 1 h after training in a nonspatial task. Synaptic changes found in the CA1 shortly after water maze training suggest a possible participation of the hippocampus in the acquisition of nonspatial tasks together with a role in the short-term consolidation of spatial memory. As no changes were found in the total number of synapses counted, it is likely that subtle changes in synaptic efficacy than new synapse generation may be sufficient to support the acquisition and mainte- nance of new memories. Synapse 59:177–181, 2006. V V C 2005 Wiley-Liss, Inc. INTRODUCTION Current models of memory consolidation (Dudai, 2004; Nader, 2003) assume that the storage of long- term memory (LTM) is associated with gene expres- sion, new protein synthesis, and synaptic remodelling. This synaptic remodelling can involve the modifica- tion of preexisting synapses or even the generation of new contacts and is proposed as a key process to explain the long-term maintenance of memories (Bai- ley and Kandel, 1993). Previous results from studies to assess the hypothesis that learning promotes mor- phological synaptic alterations are quite controversial. Specifically, there is little agreement about synaptic changes associated to spatial memory formation. On the other hand, there are strong evidences showing that a functional hippocampus is required for the acquisition of spatial tasks in the Morris water maze (MWM) (Eichenbaum et al., 1990; Morris et al., 1982). Different alterations in hippocampal synaptic transmission (e.g., long-term potentiation (LTP)) are correlated with several behavioral deficits (Jeffery, 1997). Maintenance of LTP and memory consolidation are related with an increase in multiple spine synap- ses at the hippocampus (Eyre et al., 2003; Toni et al., 1999). These evidences suggest that problems in long- term storage could be due to specific alterations in the synaptic physiology (i.e., LTP) as well as in the anatomy of synapses. However, it is not clear that in unaltered conditions, increases in synapse number are always correlated with the acquisition or consoli- dation of memories. Several methodological issues of ultrastructural studies in addition to the dynamic Contract grant sponsor: MEC; Contract grant number: SEJ2004-07445/PSIC. *Correspondence to: Ruben Miranda, Ph.D., Laboratory of Psychobiology, University of Oviedo, Plaza Feijoo, s/n 33003 Oviedo, Spain. E-mail: mirandaruben@uniovi.es Received 23 June 2005; Accepted 18 October 2005 DOI 10.1002/syn.20229 Published online in Wiley InterScience (www.interscience.wiley.com). V V C 2005 WILEY-LISS, INC. SYNAPSE 59:177–181 (2006)