Neural circuit mechanisms of defensive behaviour

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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.