Abstract
Although aversive memory has been mainly addressed by analysing the changes occurring in average populations, the study of neuronal mechanisms of outliers allows understanding the involvement of individual differences in fear conditioning and extinction. We recently developed an innovative experimental model of individual differences in approach and avoidance behaviors, classifying the mice as Approaching, Balancing or Avoiding animals according to their responses to conflicting stimuli. The approach and avoidance behaviors appear to be the primary reactions to rewarding and threatening stimuli and may represent predictors of vulnerability (or resilience) to fear. We submitted the three mice phenotypes to Contextual Fear Conditioning. In comparison to Balancing animals, Approaching and Avoiding mice exhibited no middle- or long-term fear extinction. The two non-extinguishing phenotypes exhibited potentiated glutamatergic neurotransmission (spontaneous excitatory postsynaptic currents/spinogenesis) of pyramidal neurons of medial prefrontal cortex and basolateral amygdala. Basing on the a priori individuation of outliers, we demonstrated that the maintenance of aversive memories is linked to increased spinogenesis and excitatory signaling in the amygdala-prefrontal cortex fear matrix.
Highlights
The present study evaluates how phenotypes characterized by individual differences in approach and avoidance behaviors[10,11,12] react to fear conditioning, reconsolidation, and extinction
We demonstrated that the individual differences among mice classified as approaching (AP), balancing (BA) or avoiding (AV) animals are mirrored by different tuning of cannabinoid-type 1 (CB1) signaling at the brain-wide level[11,12]
The neurobiology of fear memory and extinction has been typically studied by analyzing changes that occur in average populations[18]
Summary
The present research associates behavioral responses to fear with electrophysiological and morphological correlates in the “fear matrix” of the brain, whereby control centers, integrative sites and effector sites can be distinguished[15]. During the fear conditioning, reconsolidation, and extinction phases, the prelimbic (PL) and infralimbic (IL) subregions of the control center represented by the medial prefrontal cortex (mPFC) receive from and project back to the integrative site in the basolateral amygdala (BLA)[16]. This region in turn projects to the central nucleus (CE) of the amygdala directly or indirectly via inhibitory intercalated cells (ITC). We hypothesize that when submitted to a Contextual Fear Conditioning (CFC) test, AP and AV mice may exhibit improper fear extinction associated with altered electrophysiological and morphological correlates in the “fear matrix”
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