Synaptic tagging in the lateral amygdala fear conditioning circuit

描述(申请人提供)：听觉恐惧条件反射是一种学习范式，在这种学习范式中，大鼠可以在先前的中性音调和痛苦的刺激之间形成联系，据信是通过杏仁外侧核(LA)突触连接的持续加强而发生的，称为长时程增强(LTP)。蛋白质合成对于巩固和重新巩固恐惧条件性记忆是必要的，这可能暗示了突触重塑的作用。听觉信息通过丘脑和皮质的可塑性突触进入LA，但这些突触之间的功能和解剖关系尚不清楚。这项拟议的项目将开始研究这些突触在恐惧条件记忆中的相对作用及其结构基础。首先，使用与行为相关的诱导方案，比较皮层和丘脑输入通路对LTP巩固和再巩固的蛋白质合成的依赖性。其次，连续切片电子显微镜将被用来研究在恐惧条件反射和LTP巩固过程中LA突触的超微结构变化，包括突触大小、突触数量和局部蛋白质合成的变化。示踪剂注射将允许在所有条件下比较皮质和丘脑突触。更好地了解恐惧记忆形成和维持的突触基础，对于开发涉及恐惧联想(如恐惧症)的精神障碍干预措施非常重要。

DESCRIPTION (provided by applicant): Auditory fear conditioning, a learning paradigm in which a rat can form an association between a previously neutral tone and a painful stimulus, is believed to occur via the persistent strengthening of synaptic connections, termed long-term potentiation (LTP), in the lateral amygdala (LA). Protein synthesis is necessary for both consolidation and reconsolidation of fear conditioning memory, and this may suggest a role for synapse remodeling. Auditory information enters the LA via plastic synapses from both the thalamus and cortex, but the functional and anatomical relationship between these synapses is unclear. The proposed project will begin to investigate the relative roles of these synapses in fear conditioning memory and their structural underpinnings. First, the protein synthesis-dependence of LTP consolidation and reconsolidation will be compared between the cortical and thalamic input pathways using a behaviorally relevant induction protocol. Second, serial section electron microscopy will be used to examine ultrastructural changes in LA synapses that occur during consolidation of fear conditioning and LTP, including changes in synapse size, synapse number, and local protein synthesis. Tracer injections will allow comparison of cortical and thalamic synapses under all conditions. A better understanding of the synaptic basis of the formation and maintenance of fear memories is important for the development of interventions for psychiatric disorders involving fear associations, such as phobias.