Exposure to a novel context following contextual fear conditioning enhances the induction of hippocampal long-term potentiation

The prior behavioral experience of an animal can influence the direction and the probability of long-term plasticity induced at the activated synapses. In the present study, we compared alterations in long-term potentiation in the rat CA1 of the hippocampus following post-fear conditioning exposure to the conditioning context vs. a novel context. Furthermore, we examined whether the alterations in long-term potentiation are dependent on the prior formation of context-shock fear memory association. Whereas retrieval of fear memory 1 h after conditioning in the conditioning context was associated with impairment in the magnitude of long-term potentiation, exposure to a novel context at the same time point was associated with a robust increase in long-term potentiation. This effect was time-dependent, as exposure to a novel context 24 h after conditioning resulted in impaired long-term potentiation. Furthermore, preventing the formation of a fear context-shock association resulted in different modifications to long-term potentiation levels, regardless of whether association formation was prevented behaviorally (i.e. using a minimal context-shock association) or pharmacologically (using the N-methyl-d-aspartic acid receptor antagonist MK801). Our findings suggest that exposure to a novel environment following fear conditioning induces a form of metaplasticity that enhances the acquisition of novel information and could prevent acute stress-associated impairments in long-term potentiation.