Circuit versus stress hormonal influences in consolidation of fear memory strength and precision.

项目总结

Project Summary Discrimination between threatening and non-threatening contexts is an adaptive neurobiological process, whereas traumatic stressors may shift responses toward generalization. From a translational perspective, the loss of discrimination, or over-generalization, from a stressful to neutral context is one of the core features of stress-related psychiatric diseases. To date, many studies have made inroads in understanding memory consolidation processes in terms of overall memory strength, yet the post-learning processes that underlie discrimination vs. generalization remain poorly understood. New data from our research team suggests that limbic forebrain influences over the anteroventral bed nuclei of the stria terminalis (avBST) are poised to differentially regulate memory strength and discrimination following an aversive learning paradigm. Interestingly, these data further suggest a role for the basomedial amygdala (BMA) and rostral prelimbic (rPL) subdivision of the medial prefrontal cortex in modulating memory strength and generalization, respectively, via direct influences through avBST. Notably, activation of limbic cortical inputs to avBST supports different aspects of memory modulation, whereas the disengagement of each input may exaggerate fear memory and generalization via diminished activation over distinct circuits within avBST. This proposed work will address the hypothesis that activity in BMA/rPL–avBST circuits play distinct roles over memory strength and discrimination with both glucocorticoid-dependent and independent components. Aim 1 will address the roles of the rPL–avBST and BMA–avBST pathways and the avBST itself in modulating precision and memory strength following inhibitory avoidance learning. Aim 2 will assess whether the effects of avBST and BMA-avBST inhibition on memory consolidation depends on their effects on circulating glucocorticoids in the posttraining period. Aim 3 will focus on the sites of action within specific circuits in which glucocorticoids are having their effects on memory strength and/or precision. These findings will be instrumental for improving our understanding of how these circuits influence memory strength vs. precision in the period following an aversive learning experience and determine the degree to which these effects depend on alterations in glucocorticoids vs. direct influences on neuronal processes within the brain.