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

项目摘要 区分威胁性和非威胁性语境是一个适应性神经生物学过程， 而创伤性应激源可能会使反应转向泛化。从翻译的角度来看， 从有压力的环境到中性环境的消除歧视，或过度概括，是 压力相关的精神疾病。到目前为止，许多研究在理解记忆方面取得了进展 在整体记忆强度方面的巩固过程，以及作为基础的学习后过程 歧视与泛化之间的关系仍然知之甚少。我们研究小组的新数据表明 边缘前脑对终纹前腹侧床核的影响 遵循厌恶的学习范式，以不同的方式调节记忆强度和辨别力。有趣的是， 这些数据进一步提示杏仁基底内侧核(BMA)和吻侧前交叉核(RPL)在大脑中隔核中的作用。 内侧前额叶皮质对记忆强度和概括性的直接影响 通过avBST。值得注意的是，激活边缘皮质对avBST的输入支持记忆的不同方面 调制，而每个输入的脱离可能夸大恐惧记忆和概括 AvBST内不同回路上的激活减少。这项拟议的工作将解决以下假设 BMA/RPL-avBST环路的活动对记忆强度和辨别能力有明显的影响 糖皮质激素依赖和独立成分。目标1将阐述RPL-avBST和 BMA-avBST通路和avBST本身在抑制后的调制精度和记忆强度中的作用 回避学习。目标2将评估avBST和BMA-avBST抑制对记忆的影响 巩固取决于它们在训练后对循环中糖皮质激素的影响。目标3将专注于 关于糖皮质激素对记忆强度有影响的特定回路中的作用部位 和/或精确度。这些发现将有助于我们更好地理解这些回路是如何 在一次令人厌恶的学习经历之后的一段时间内，影响记忆强度与精确度，并确定 这些效应依赖于糖皮质激素变化的程度与对神经元的直接影响 大脑内部的过程。

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.