Pharmacological and Genetic Modulation of Episodic-like Memory in the Mouse

Rationale NMDA-R (N-methyl-D-aspartate receptors) havebeen implicated in synaptic plasticity underlying one-triallearning of event-place associations. In rodents, episodic-like memory (ELM) of personally experienced events canbe inferred from behavior that reflects the remembrance ofthe content (what kind of object was presented), place(where was this object placed), and temporal context (whenwas the object presented). We have previously shown thatthat D-cycloserine (DCS), an NMDA-R agonist, amelioratesstress-induced deficits in ELM.Objectives In this study, we used an experimental protocoldesigned to detect promnestic drug effects and investigatedwhether DCS, which is known to enhance learning andmemory, can induce ELM under conditions where micenormally do not show ELM.Results Mice that have been treated i.p. with DCS (20 mg/kg)both remembered the temporal order in which two differentobjects had been encountered during two consecutive sampletrials, as well as their spatial position during the sample trials.Most importantly, the test trial performance of these mice iscompatible with ELM in terms of an integrated memory forunique experiences comprising “what”, “where”, and “when”information. In contrast, mice that have received either a salineinjection or lower doses of DCS (0.2 and 2.0 mg/kg) did notshow such an integrated ELM.Conclusions To our knowledge, this is the first reportshowing that DCS can promote ELM in mice.