Basolateral amygdala projections in the modulation of memory consolidation

基底外侧杏仁核投射在记忆巩固调节中的作用

• 批准号: 9756551
• 负责人: Krista Wahlstrom
• 金额: $ 3.52万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756551
• 关键词: Address; Affect; Affective; Amygdaloid structure; Area; Axon; Behavioral; Brain region; Ca(2+)-Calmodulin Dependent Protein Kinase; Cations; Chlorides; Complex; Cues; Disease; Dorsal; Emotional; Environment; Event; Female; Foundations; Frequencies; Future; Halorhodopsins; Hippocampus (Brain); Immunoblotting; Impairment; Implant; Injury; Knowledge; Lateral; Learning; Light; Lighting; Location; Medial; Mediating; Memory; Opsin; Optics; Pathway interactions; Phosphorylation; Physiologic pulse; Procedures; Process; Protein Analysis; Proteins; Publishing; Pump; Rattus; Regulation; Research; Role; Sprague-Dawley Rats; Structure; Taste aversion; Testing; Training; Viral; Work; base; calmodulin-dependent protein kinase II; conditioned fear; entorhinal cortex; experimental study; information processing; insight; male; memory consolidation; memory process; memory recognition; neural circuit; novel; object recognition; optical fiber; protein expression; response; water maze

Abstract Evidence indicates that the basolateral complex of the amygdala (BLA) modulates memory consolidation following many types of learning, including inhibitory avoidance, contextual fear conditioning, conditioned taste aversion, cued and spatial water maze tasks, and object recognition. Yet how the BLA engages in such promiscuous modulation remains unclear. Recent evidence suggests that the activity of discrete BLA subpopulations, as defined by their projection targets, is critical for how the BLA influences information processing across a variety of affective and mnemonic capacities. For example, BLA projections to the ventral hippocampus influence the consolidation of the emotional (footshock-based) component of contextual fear conditioning, but not the contextual component. Conversely, my own now-published findings suggest that BLA projections to the medial entorhinal cortex (MEC) are involved in the consolidation of spatial/contextual learning in a selective manner. Based on my initial findings, this proposal will 1) examine BLA projections to the MEC in the regulation of activity-regulated cytoskeletal-associated protein (ARC) and calcium/calmodulin-dependent protein kinase (CaMKII) in relation to spatial learning and 2) investigate BLA projections to the MEC and the lateral entorhinal cortex (LEC) in the consolidation of two different kinds of object-based learning. In the first set of experiments, male and female Sprague-Dawley rats will undergo behavioral training on a spatial or cued- response Barnes maze task followed by immediate posttraining optical stimulation of the BLA-MEC pathway. Rats with either be tested for retention 2 d later or sacrificed for protein analysis. In particular, I will examine changes in ARC and CaMKIIα protein expression in the dorsal hippocampus as a consequence of BLA-MEC stimulation, as I hypothesize that BLA influences on MEC activity immediately after training provide the circuitry mechanism by which the BLA influences ARC and CaMKIIα protein expression in the dorsal hippocampus. In a second set of experiments, rats will be trained on an object-based task, followed by immediate posttraining optical manipulation of the BLA-MEC or BLA-LEC pathway. Retention will be tested 24 h later in either an object- in-location retention test or a novel-object recognition retention test. Based on previous work, we expect altering activity in each pathway will selectively influence the consolidation of one type of object-based learning but not the other, thus dissociating BLA influences on each type of learning. The findings from this proposal will be instrumental in understanding the circuitry by which the BLA contributes to the modulation of ARC and CaMKIIα in downstream structures and in elucidating the neural circuits by which the BLA modulates the consolidation of different types of memory.

摘要