Rethinking memory dynamics: the role of synaptic cooperation and competition in fear memory maintenance

Understanding how information is processed and stored in the brain, is understanding who we are. Learning is a key process allowing individuals to adapt to the environment. It is now well accepted that information storage in the form of long-term memories LTM involves a process of consolidation, in which labile memories are stabilized as long-lasting traces. Although one can consider each learning event as the acquisition of a ?new? memory, considerable evidence indicates that new memories are formed in an interleaved fashion upon a large network of pre-existing knowledge. This implies that learning is highly influenced by previous experience and that previously consolidated memories can be reactivated during new learning. Once active, a previously acquired memory can be strengthened by the following event, by cooperation, or can be lost, by competition. Thus, memories are very dynamic entities that evolve over time. The rules by which memory cooperation and competition are orchestrated and what determines which trace is stored as a long-term memory, are completely unknown.

We aim to address the rules by which memories interact with each other by cooperation and competition. Using as a model the discriminative fear learning, we aim to understand how memories are acquired but most importantly, how they are maintained when conflicting information is presented. Our proposal combines electrophysiological analysis of neuronal networks involved in discriminative fear memories, together with optogenetic manipulations of neuronal activation in freely behaving animals. We will focus on amygdala-dependent learning since this brain area is very well known from the anatomical and behavioural point of view. This will allow us to combine the information obtained from neuronal physiology with the behavioural analysis to conceive strong predictive models of memory dynamics. We have a strong indication that the endocannabinoid signalling is involved in modulating memory dynamics. Since the role of the endocannabinoid system in modulating anxiety disorders and post-traumatic stress disorders is very well known, we will explore the hypothesis that by modulating memory dynamics we may pave the path to better clinical interventions in this group of psychiatric disorders.