Hypothalamic CRH neurons and the control of innate behaviour

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Navigating the world requires that all organisms make decisions and execute behaviors that are context appropriate. In some situations, an instantaneous decision with little or no prior knowledge of the situation, is required. For example, when faced with an unknown threat, the animal must recognize the threat, compute threat level and then choose from a palette of behaviors. These may be innate (unlearned) or learned behaviors. The correct choice is necessary to ensure survival. How do innate and learned behaviors intersect? Are there specific conditions under which animals prioritize one above another? The current view is that innate behaviors are prioritized over learned survival tactics. Yet, our preliminary work suggests that this hierarchy can be disrupted. Here we will ask whether specific behavioral training can shift these innate strategies by modifying the output of neural networks that are critically involved in both learned and innate behavior. We will use mice as a model to investigate innate defensive/survival behaviors; our paradigm mimics threat descending from above (flying predators). This looming and descending shadow mimics an increase in threat imminence from an approaching predator; it requires visual information processing and drives defensive behavior - either an escape targeted to a shelter, or freezing. In lab mice, with no prior experience with a predator task, the response is the consequence of accessing an unlearned behavioral repertoire. Our preliminary data indicate that CRH neurons in the paraventricular nucleus of the hypothalamus increase their activity in response to a looming shadow and appear to anticipate the behavioral decision to escape. We will ask whether that this ramping in the neuronal activity signature of CRH neurons is an anticipatory component of a preparatory sequence of events that allows the animal to make a calculation that culminates in escape behavior. We also have compelling evidence that the activity of CRH neurons to anticipate escape can be modified through instrumental learning paradigms that are unrelated to the looming predator, but rely on a neutral cue prior to an aversive stimulus. This indicates that these cells may be an intersectional node that links innate and learned behavior. Recent work from our lab, and other, shows that CRH neurons may be part of a subcortical, or bottom-up circuit that relays information about the state of the organism to higher brain regions. Here we propose to use innate and learned behavioral paradigms, combined with in vivo fibre photometry, optogenetics, a newly developed machine learning algorithm for assessing spontaneous behaviors and in vitro electrophysiology to test the hypothesis that instrumental controllability training alters CRH neuron activity to shift innate behavioral priorities.