Influence of the locus coeruleus on fear learning and threat processing in the ventral hippocampus

蓝斑对腹侧海马恐惧学习和威胁处理的影响

基本信息

批准号：
10552594
负责人：
Brian J Wiltgen
金额：
$ 19.41万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-20 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10552594
关键词：
Acute American Amygdaloid structure Anxiety Anxiety Disorders Attention Attention deficit hyperactivity disorder Behavior Behavioral Bipolar Disorder Brain region Catecholamines Cells Cognitive Disease Environment Fiber Follow-Up Studies Fright Goals Hippocampus Hormones Human Hypothalamic structure Image Lateral Learning Lesion Mediating Memory Memory impairment Mental disorders Monitor Neurons Output Pathway interactions Phase Photometry Physiological Play Process Production Research Role Schizophrenia Shock Signal Transduction Stimulus Stress Structure System Testing Training United States United States National Institutes of Health anxiety reduction anxiety-related behavior cell type comorbidity conditioned fear experience experimental study follow-up in vivo in vivo calcium imaging interdisciplinary approach locus ceruleus structure neural neuromechanism neuroregulation novel optogenetics prevent response transmission process

项目摘要

Abstract The locus coeruleus (LC) and ventral hippocampus (vHPC) both influence our response to threatening stimuli. Research to date has focused primarily on the contribution each of these structures makes to fear learning and anxiety. However, few studies have examined the interactions that occur between the LC and vHPC during threat processing. The LC is typically thought to provide a salience signal to the HPC and other brain regions, that enhances plasticity and facilitates memory formation. However, the LC and vHPC have also been shown to drive innate anxiety-related behaviors in stressful situations. To resolve this apparent discrepancy, we will test the novel idea that fear learning and innate anxiety are both controlled by distinct oscillations in the LC (phasic vs tonic firing) that are transmitted to the vHPC when a threat is encountered. Acute, fear-inducing stimuli have been shown to produce large, transient responses in the LC and the vHPC. For example, aversive footshock produces phasic activity in both structures that can persist for up to several seconds after the stimulus has terminated. As phasic LC responses are typically associated with focused attention and the encoding of salient stimuli, we hypothesize that phasic activity in the LC promotes fear learning by enhancing shock processing in the vHPC. In contrast, situations that induce anxiety, such as open, unsheltered environments, produce smaller, but longer lasting increases in tonic activity in the LC. Consequently, we hypothesize that the LC elicits anxiety-related behaviors when a potential threat is encountered by inducing tonic firing in the vHPC. To test these ideas, we will use a multidisciplinary approach that combines in vivo fiber photometry with cell-type specific optogenetics to simultaneously monitor vHPC activity while manipulating LC neurons during fear conditioning and situations that provoke anxiety. Follow-up studies will build on these results by using in vivo calcium imaging to determine the effects of tonic and phasic LC firing on the activity of shock-responsive and anxiety-responsive cells in the vHPC.

抽象的蓝斑 (LC) 和腹侧海马 (vHPC) 都会影响我们对威胁刺激的反应。迄今为止的研究主要集中在这些结构对恐惧学习和恐惧的贡献上。焦虑。然而，很少有研究考察 LC 和 vHPC 之间发生的相互作用。威胁处理。 LC 通常被认为向 HPC 和其他大脑区域提供显着信号，增强可塑性并促进记忆形成。然而，LC 和 vHPC 也已被证明在压力情况下驱动与生俱来的焦虑相关行为。为了解决这个明显的差异，我们将测试恐惧学习和先天焦虑都是由 LC 中不同振荡控制的新想法（阶段性与强直性射击）在遇到威胁时传输到 vHPC。急性的、引起恐惧的刺激已被证明会在 LC 和 vHPC 中产生大的瞬时反应。例如，厌恶足部震动会在两个结构中产生阶段性活动，这种活动可以在足部震动后持续数秒。刺激已经终止。由于阶段性 LC 反应通常与集中注意力和编码显着刺激，我们假设 LC 中的阶段性活动通过增强恐惧学习来促进恐惧学习。 vHPC 中的冲击处理。相反，会引起焦虑的情况，例如开放、无遮挡的情况环境中，LC 中的强直活动产生较小但更持久的增加。因此，我们假设当遇到潜在威胁时，LC 通过诱导而引发焦虑相关行为 vHPC 中的补品放电。为了测试这些想法，我们将使用结合体内纤维的多学科方法使用细胞类型特异性光遗传学进行光度测定，在操作 LC 的同时同时监测 vHPC 活性恐惧调节和引起焦虑的情况下的神经元。后续研究将在此基础上进行通过使用体内钙成像来确定强直性和阶段性 LC 放电对活性的影响，得出结果 vHPC 中的休克反应细胞和焦虑反应细胞。