A role for the interpeduncular nucleus in innate defensive behaviors

脚间核在先天防御行为中的作用

• 批准号: 10558615
• 负责人: ANDREW R TAPPER
• 金额: $ 20.94万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 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/10558615
• 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; Darkness; Data; Detection; Disease; Etiology; Exposure to; Extinction; Fiber; Fishes; Freezing; Fright; Goals; Halorhodopsins; Head; Human; Impairment; Laboratory Animals; 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; neuropathology; novel; optogenetics; response; sensor; sound; stressor; visual stimulus

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.

项目摘要/摘要 对潜在威胁的反应和与生俱来的防御行为对生存至关重要。尽管如此，过度- 大脑防御网络的激活，更重要的是，灭绝的损害(即 在没有令人厌恶的刺激的情况下，减少对重复暴露的威胁反应)可以导致 与焦虑症相关的行为适应不良和神经病理状况。因此， 识别潜在的先天威胁处理的神经元电路和机制，特别是， 对反复暴露的防御行为的抑制是理解健康大脑的基础 对威胁性刺激的反应，以及对焦虑症等病理情况的洞察。 虽然大多数对实验室动物的研究都集中在非自然主义的对威胁的条件性反应上 情况下，暴露在头顶上的黑暗视觉隐约刺激(VLS)中自然会引发天生的防御 跨多个物种的反应。最近的研究确定了内侧缰核-脚间神经 核团(MHB-IPN)轴与条件性恐惧有关，并可能特别有助于 由于与线索和/或上下文的关联而导致的冻结行为。然而，IPN是否明确 对先天防御反应的贡献尚不清楚。这个应用程序的目标是测试总体架构 威胁处理和适应性抑制性学习需要特定的IPN GABA能模式的假设 神经元激活与外侧背侧被盖传入胆碱能神经元对内源性胆碱能的调节 防御性反应。AIM 1将结合钙传感器、纤维光度测量和光遗传方法来 检验IPN GABA能神经元被多感觉诱发防御行为激活的假说 和先天抑制性学习；然而，Aim 2将使用类似的方法来测试IPN GABA能 神经元和先天防御行为受LDTg对IPN的兴奋性输入的调节。如果承担的话 这些实验的结果应该会揭示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。