The hippocampus plays a critical role at encoding discontiguous events for subsequent declarative memory expression in mice

The hypothesis that hippocampal activity at encoding is causally related to subsequent declarative memory expression is tested in the mouse, by using lidocaine inactivation of the hippocampus in combination with c‐fos neuroimaging analysis. We employed a two‐stage radial maze paradigm of spatial discrimination, which was previously shown to dissociate between declarative and nondeclarative expression of memory related to the same acquired material. In Stage 1 (encoding), mice learnt the constant location of food among a set of six arms (three baited, three unbaited) by being submitted repeatedly to discontiguous experiences with each arm separately (“go/no‐go” discrimination). In Stage 2 (test‐session), they are challenged with novel presentations of the arms, which are either combined into pairs of opposite valence (“two‐choice” discrimination), or opened all six together (“six‐choice” discrimination). Previous experiments have demonstrated that the “two‐choice” situation is a critical test for declarative memory while “six‐choice” discrimination may rely on procedural memory. We observed that (i) hippocampal activity measured by c‐fos mRNA expression was increased by “go/no‐go” learning, and this activation was blocked by pre‐training local infusions of lidocaine; (ii) when performed just before each session of Stage 1, such inactivation spared the acquisition of “go/no‐go” discrimination but produced, subsequently, a selective deficit in the “two‐choice” test (not in the “six‐choice” test). This study indicates that the hippocampus is “spontaneously” engaged in encoding processes necessary for long‐term storage of discontiguous experiences under a form enabling flexible declarative memory expression. © 2007 Wiley‐Liss, Inc.