As fear can be generated and increased by learning processes, likewise also learned fear inhibition mechanisms do exist. Conditioned inhibition of fear is a fear inhibitory mechanism which involves learning of safety signals and is therefore also referred to as “learned safety”. Learned safety signals exert effects beyond the regulation of fear responses and the identification of episodes of security: they also relate to positive affective states, elicit reward-related approach and a reduction of depression-like behavior in mice. Hence, learned safety can be used as paradigm within the sub-construct “reward prediction” of the “positive valence” system along the newly established Research Domain Criteria system (RDoc) for neuropsychiatric research
While some selected insights into the mediating neural underpininngs have been obtained and evidence for its translational potential exist, the molecular mechanisms of learned safety remain incompletely understood. The present thesis examined the role of microRNAs (miRNAs) - small noncoding RNAs which modulate gene expression at the posttranscriptional level - in learned safety. Specifically, the contribution of selected miRNA species (of the miR-212/132 family) to the behavioral expression of learned safety was investigated. In-silico and in-vitro approaches were then combined to identify possible relevant target genes of miRNA-132 which could be mediating the neural effects of learned safety.
The present data integrate a wide range of analytical levels of the behavioral state of learned safety with a focus on some relevant molecular processes. Within the RDoc framework, the obtained information may contribute to enhance our understanding of one of the basic domains of functioning which is present along a grading spectrum of behavior - from physiology to pathology of the brain and its behavioral expression.