A role for the interpeduncular nucleus in innate defensive behaviors

脚间核在先天防御行为中的作用

基本信息

批准号：
10467285
负责人：
ANDREW R TAPPER
金额：
$ 25.13万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
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：
2022-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10467285
关键词：
Acute Adult Anxiety Anxiety Disorders Auditory Aversive Stimulus Axon Behavior Behavioral Brain Calcium Calcium Signaling Cell Nucleus Cells Choline O-Acetyltransferase Conditioned Reflex Cues Data Detection Disease Etiology Exposure to Extinction (Psychology)Fiber Fishes Freezing Fright Goals Halorhodopsins Human Impairment Laboratory Animals Lead Learning Medial Monitor Mus Neurons Nicotine Withdrawal Pathologic Pattern Photometry Play Process Proxy Psyche structure Recurrence Response to stimulus physiology Rodent Role Shapes Shelter facility Stimulus Testing United States Viral Visual Visual Fields Work anxiety-like behavior cholinergic clinical heterogeneity conditioned fear disability experimental study hindbrain in vivo insight interpeduncular nucleus laterodorsal tegmentum multisensory nerve supply neuronal circuitry novel optogenetics response sensor sound stressor visual stimulus

项目摘要

Project Summary/Abstract Responses to potential threat and innate defensive behaviors are critical for survival. Nevertheless, an over- activation of the brain defensive network and, more importantly, an impairment in extinction (i.e., the ability to reduce threat responding upon repeated exposures in the absence of an aversive stimulus) can lead to behavioral maladaptation and neuropathological conditions associated with anxiety disorders. Thus, identification of the neuronal circuits and mechanisms underlying innate threat processing and, in particular, inhibition of defensive behaviors upon recurrent exposures, is fundamental for understanding the healthy brain response to threatening stimuli and also for insights into pathological conditions such as anxiety disorders. While most studies in laboratory animals have focused on conditioned responses to threat in non-naturalistic situations, exposure to an overhead dark visual looming stimulus (VLS) naturally elicits innate defensive responses across multiple species. Recent studies have determined that the medial habenulo-interpeduncular nucleus (MHb-IPN) axis has been implicated in conditioned fear and may contribute specifically to extinction of freezing behavior induced by associations with a cue and/or context. However, whether the IPN specifically contributes to innate defensive responses is unknown. The goal of this application is to test the over-arching hypothesis that threat-processing and adaptive inhibitory learning require specific patterns of IPN GABAergic neuron activation and afferent cholinergic input from the laterodorsal tegmentum (LDTg), to modulate innate defensive responses. Aim 1 will combine calcium sensors, fiber photometry and optogenetic approaches to test the hypothesis that IPN GABAergic neurons are activated by multi-sensory evoked defensive behaviors and innate inhibitory learning; whereas, Aim 2 will use similar approaches to test if activation of IPN GABAergic neurons and innate defensive behaviors are modulated by excitatory input to the IPN from the LDTg. If borne out, the results of these experiments should reveal novel cellular and circuit mechanisms underlying the response to naturalistic fearful stimuli and the effect of these mechanisms on innate defensive behaviors.

项目概要/摘要对潜在威胁和先天防御行为的反应对于生存至关重要。尽管如此，一个过度大脑防御网络的激活，更重要的是，灭绝的损害（即，能力）减少在没有厌恶刺激的情况下重复暴露时的威胁反应）可能会导致与焦虑症相关的行为适应不良和神经病理学状况。因此，识别先天威胁处理背后的神经回路和机制，特别是反复暴露时抑制防御行为是了解健康大脑的基础对威胁性刺激的反应，以及对焦虑症等病理状况的洞察。虽然大多数实验动物研究都集中在非自然威胁下的条件反应在这种情况下，暴露于头顶上的黑暗视觉刺激（VLS）自然会引发本能的防御跨多个物种的反应。最近的研究表明，内侧缰核-脚间神经核（MHb-IPN）轴与条件性恐惧有关，可能特别有助于灭绝冻结由与提示和/或上下文关联引起的行为。然而，IPN 是否具体对先天防御反应的贡献尚不清楚。该应用程序的目标是测试总体假设威胁处理和自适应抑制学习需要 IPN GABAergic 的特定模式神经元激活和来自后背被盖 (LDTg) 的传入胆碱能输入，以调节先天性防御性反应。目标 1 将结合钙传感器、光纤光度测定和光遗传学方法检验 IPN GABA 能神经元被多感官诱发的防御行为激活的假设和先天抑制学习；而目标 2 将使用类似的方法来测试 IPN GABAergic 是否激活神经元和先天防御行为由 LDTg 对 IPN 的兴奋性输入进行调节。如果承担显然，这些实验的结果应该揭示了潜在的新的细胞和电路机制对自然恐惧刺激的反应以及这些机制对先天防御行为的影响。