Abstract
The brain integrates stimuli from both the internal and external environments to generate appropriate physiological and behavioural responses. Such responses can include seeking food in states of hunger or seeking safety in states of fear. However, when these states are presented simultaneously or in conflict with one another, only one behavioural response can be selected. How the brain selects the appropriate behavioural response in the presence of conflicting stimuli is not well understood. In this thesis, we explore this using a novel behaviour test that creates conflicting motivations, a need for food and a need for safety. Using this model, the overall aim of this thesis is to understand how stress neural signals influence safety-seeking behaviours.
In this project, we developed a foraging task in which fed or fasted mice can explore a potentially dangerous environment to find food. We found that mice avoided the foraging area and preferred to remain in safety when an external stressor (air puff) was applied. In contrast, the preference for safety in response to the air puff was not observed in fasted mice. This suggested that increased motivation for food can overcome the drive to seek safety. We next sought to determine whether artificially inducing a stress state is sufficient to cause safety-seeking behaviours and whether fasting can also overcome this effect.
Detection of a real or perceived threat causes the activation of corticotropin-releasing hormone (CRH) neurons in the hypothalamus. Although CRH neurons have been implicated in stress-related behavioural responses, few studies have established a role for CRH neurons in directly causing these changes. Therefore, the second aim was to establish a causal relationship between CRH neurons and changes in safety-seeking behaviours. To do this we used chemogenetics to specifically target and artificially activate CRH neurons. We found that chemoactivation of CRH neurons was sufficient to cause safety-seeking behaviours and thus reduced time foraging. However, despite artificially inducing a stress state, fasted mice did not show an increase in safety-seeking behaviours.
Overall, we have validated the foraging task for measuring changes in state-driven behaviours in the presence of conflicting motivations (i.e. stress and hunger). We have also demonstrated a causal role of CRH neurons in the generation of safety-seeking behaviours.
However, we report that in the presence of other needs, such as hunger, the effect of CRH neuron stimulation on behaviour is diminished.