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

摘要 蓝斑(LC)和腹侧海马区(VHPC)都影响我们对威胁刺激的反应。 到目前为止，研究主要集中在这些结构中的每一种对恐惧学习和 焦虑。然而，很少有研究研究LC和vHPC之间的相互作用 威胁处理。LC通常被认为向HPC和其他大脑区域提供显著信号， 这增强了可塑性，促进了记忆的形成。但是，LC和vHPC也已显示 在有压力的情况下推动与生俱来的焦虑相关行为。为了解决这一明显的差异，我们将 测试恐惧学习和天生焦虑都是由LC中不同的振荡控制的新想法 在遇到威胁时传输到vHPC。尖锐的，令人恐惧的 刺激已被证明在LC和vHPC中产生大的瞬时反应。例如，厌恶 足底电击在两个结构中产生相性活动，在运动后可持续几秒钟 刺激计划已经终止。由于阶段性LC反应通常与注意力集中有关，而 编码显著刺激，我们假设LC中的阶段活动通过增强 VHPC中的冲击处理。相比之下，导致焦虑的情况，如开放的，没有庇护 在环境中，LC中的补药活性会产生较小但更持久的增加。因此，我们 假设LC在遇到潜在威胁时会引发焦虑相关行为 在vhpc中发射主音。为了测试这些想法，我们将使用一种结合体内纤维的多学科方法 利用细胞型特定光遗传学在操作LC的同时监测vHPC活性的光度学 在恐惧条件反射和引发焦虑的情况下的神经元。后续研究将建立在这些基础上 结果采用体内钙显像法测定强直性和相性LC放电对心肌细胞活性的影响。 VHPC中的休克反应细胞和焦虑反应细胞。

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.