Hippocampal α-calcium/calmodulin-dependent protein kinase II (αCaMKII) has been implicated in neuronal plasticity and spatial learning. In the present experiment, an adeno-associated virus (AAV) vector was designed to express αCaMKII driven by the U6 promotor. Microinfusion of this vector into the rat hippocampus increased αCaMKII immunoreactivity by ∼73% (Western analysis) and improved performance in a water maze task. Locomotor activity and exploratory behavior in an open field task were not altered by the overexpression of αCaMKII. These data support a role for αCaMKII in spatial or explicit memory storage. The advantages of viral vectors for manipulating target proteins expression compared with genetically modified mouse models are discussed. © 2006 Wiley-Liss, Inc.