In contextual fear conditioning (CFC) the environmental context can signal the occurrence of an aversive stimulus (US). This association leads to fear conditioned responses (CR) when it is re-exposed to the context. It is thought that these conditioned memories are encoded by a strengthening of synaptic connections between neurons that are active at the time of CFC, forming neuronal ensembles in a distributed brain network that would reactive for retrieval. Previous stimuli can also have the power of predictability and then the salience to be associated to a posterior US. It has been demonstrated that a previously experienced context can be associated separated by a time interval of 5 s from a posterior US. However, the neurobiology of this and other associations discontinuous in time have been mostly studied by approaches based in the function of single regions at specific time points. Thus, it is unclear the effect of the time factor, that may include the maintenance of the stimulus over time, in the interplay among different brain regions to form a stable memory trace. Because prelimbic cortex (PL), a subdivision of medial prefrontal cortex (mPFC), is necessary for maintain information over time, has persistent fire, bridges signal during time intervals and has firing patterns related to the environment, neurons of PL could be part of the engram of associations discontinuously in time, and so, in a distinctive manner when compared to delay associations. The aim of the present study is to investigate the neuronal ensemble that encode and retrieve CFC with temporal discontinuity, comparing it to that of CFC. For this, we will use c-Fos-tTA mice to permanently tag neurons active in mPFC, amygdala and hippocampus in encoding and their reactivation in retrieval to measure their overlap and infer a stable memory trace of each task. It will be further investigated if the optogenetic stimulation of potential neuronal ensembles in PL is sufficient to drive CR and to promote the reactivation of other parts of the previously determined engram.
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