Neural circuit mechanisms of defensive behaviour

跨物种的生存取决于识别威胁情况和部署防御行为的能力，如逃跑或冻结。解释啮齿动物选择这些防御行为的一个重要理论是捕食迫在性，该理论预测一种行为将取决于捕食者或威胁刺激的接近程度。这些威胁性的情况使中脑导水管周围灰质(PAG)的亚区在一个广泛的地形图组织中发挥作用，以至于PAG背侧控制逃逸，腹侧PAG控制冻结。尽管很容易观察到冰冻和逃跑，但行为学研究表明，动物将几个刻板的行为模块组合成序列，以满足环境需求。然而，大多数防御性行为研究只关注逃脱或冻结。因此，对完整的防御行为的研究较少，其穿过PAG背腹轴的神经底物也是未知的。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，以揭示一系列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，从而能够检查PAG神经活动和行为表达之间的动态关系。这项建议将结合行为建模、神经记录和光遗传操作来研究PAG中各种防御行为的功能组织。我们将在先天和后天的防御行为任务中识别行为音节及其表达的结构。我们将记录在音节表达过程中跨PAG背腹轴的神经回路活动，以了解音节在PAG中的功能映射。具体地说，这些研究将检验PAG的侧部区域是否支持中等威胁级别的行为，此时既没有表现出逃脱，也没有表现出冻结。最后，我们将操纵PAG背腹亚区的特定回路，以确定它们在产生防御行为音节中的作用及其表达顺序。这个项目将：(A)证明防御行为是语法的(B)识别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和(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来解释和预测整个行为和威胁过程中的防御反应。

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.