Neural circuit mechanisms of defensive behaviour

防御行为的神经回路机制

• 批准号: RGPIN-2022-04214
• 负责人: Rozeske, Robert
• 金额: $ 2.11万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764219
• 关键词: Neural; circuit; mechanisms; defensive; behaviour

Across species survival depends on the ability to recognize threatening situations and deploy defensive behaviours such as flight or freezing. A prominent theory to explain the selection of these defensive behaviours in rodents is predatory imminence, which predicts a behaviour will be expressed depending on the proximity of the predator or threatening stimulus. These threatening situations engage subregions of the periaqueductal gray (PAG) in a broadly topographic organization such that the dorsal PAG controls escape and the ventral PAG controls freezing. Although freezing and escape are readily observable, ethological studies suggest that animals combine several stereotyped behavioural modules into sequences to address environmental demands. Yet most defensive behaviour research focuses solely on escape or freezing. Consequentially, the full defensive behaviour repertoire is less studied, and its neural substrates across the dorsoventral axis of the PAG are unknown. Recent modeling studies confirm that behaviour is composed of mutually exclusive behavioural "syllables" that are arranged into sequences with a reliable structure, or grammar. We will systematically apply these methods to defensive behavioural tasks to uncover the diversity of syllables across a range of threat-levels, and their grammar. Deconstructing defensive responses will provide discrete behavioural targets that will allow examination of the dynamic relationship between PAG neural activity and behavioural expression. This proposal will combine behavioural modeling, neural recordings, and optogenetic manipulations to investigate the functional organization of a diversity of defensive behaviours in the PAG. We will identify behavioural syllables and the structure of their expression during innate and learned defensive behaviour tasks. We will record neural circuit activity across the dorsoventral axis of the PAG during syllable expression to understand how syllables are functionally mapped in the PAG. Specifically, these studies will examine whether the lateral regions of PAG support behaviours during medium threat-levels, when neither escape or freezing are expressed. Finally, we will manipulate defined circuits in PAG dorsoventral subregions to determine their role in generating defensive behaviour syllables and the sequence of their expression. This project will: (A) show that defensive behavior is grammatical (B) identify the neural mechanisms that generate behavioral syllable expression (C) predict future defensive reactions based upon the present behavioral syllable and (D) provide a framework to study how factors such as context, satiety, age, sex, and stress alter defensive behaviour. Together, this project will develop a neurobiological model to explain and predict defensive responses throughout behavioural and threat continua.

跨物种的生存取决于识别威胁情况和部署防御行为（如飞行或冻结）的能力。一个解释啮齿类动物选择这些防御行为的突出理论是捕食临近性，它预测一种行为将根据捕食者或威胁刺激的接近程度而表达。这些威胁性的情况下从事次区域的导水管周围灰质（PAG）在一个广泛的地形组织，如背侧PAG控制逃避和腹侧PAG控制冻结。虽然冻结和逃跑是很容易观察到的，行为学研究表明，动物联合收割机几个刻板的行为模块组合成序列，以应对环境的需求。然而，大多数防御行为研究仅仅关注逃跑或冻结。因此，对完整的防御行为库的研究较少，并且其跨PAG背腹轴的神经基质也未知。 最近的建模研究证实，行为是由相互排斥的行为“音节”组成的，这些音节被安排成具有可靠结构或语法的序列。我们将系统地将这些方法应用于防御行为任务，以揭示各种威胁级别的音节及其语法的多样性。解构防御反应将提供离散的行为目标，这将允许检查PAG神经活动和行为表达之间的动态关系。该提案将结合联合收割机行为建模，神经记录和光遗传学操作来研究PAG中多种防御行为的功能组织。我们将确定行为音节和他们的表达在先天和后天防御行为任务的结构。我们将记录音节表达过程中PAG背腹轴的神经回路活动，以了解音节在PAG中的功能映射。具体而言，这些研究将检查PAG的侧区域是否支持中等威胁水平期间的行为，当逃避或冻结都没有表达。最后，我们将操纵定义的PAG背腹侧亚区的电路，以确定其在产生防御行为音节和序列的表达中的作用。该项目将：（A）表明防御行为是合乎语法的（B）确定产生行为音节表达的神经机制（C）根据当前的行为音节预测未来的防御反应（D）提供一个框架来研究环境、饱腹感、年龄、性别和压力等因素如何改变防御行为。该项目将共同开发一个神经生物学模型，以解释和预测整个行为和威胁连续体的防御反应。