Role of the ventromedial hypothalamus in control of innate defensive behaviours
Our senses are constantly bombarded with information. How does the brain integrate such a variety of inputs to generate appropriate behaviours? Innate defensive behaviours are a good model to address this question. They are essential for animal survival and the brain circuits that control them are highly conserved across species. Moreover, the sensory inputs and behavioural outputs can be well defined and reliably reproduced in the lab. This allows us to study function of the individual components of the circuit controlling these behaviours. Ventromedial hypothalamus (VMH) is a key brain region for controlling responses to predators; it has been shown that inactivating the VMH can reduce defensive behaviours. Interestingly, activating the VMH output neurons (SF1+ cells) can produce a variety of different behaviours, from immobility to escape, depending on the intensity of activation. During my PhD I used a variety of approaches to address the question of the function of the VMH in control of defensive behaviours. At first I hypothesised that the VMH might act as a centre responsible for choosing an appropriate behavioural response according to the stimulus. I set to investigate how different activation levels of SF1+ neurons can produce such different behavioural outputs, and how this activity is modulated in vivo in response to predator stimuli. I began the project by quantifying mouse defensive behaviours in response to olfactory and auditory predator cues, as well as to the optogenetic activation of SF1+ neurons. I then questioned whether there was heterogeneity within the population of SF1+ neurons, which could explain their ability to trigger different behaviours. I performed patch clamp recordings from acute brain slices and conducted a study of the electrophysiological properties of SF1+ neurons. I next investigated how SF1+ neurons integrate excitatory inputs from the medial amygdala, a region which receives olfactory inputs from the accessory olfactory bulb. By combining optogenetics with slice electrophysiology and behavioural assessment, I described the physiology and relevance of this connection. Finally, I investigated in vivo activity in the VMH in response to predator cues by performing calcium imaging of the VMH neurons in freely moving mice. By presenting different sensory stimuli, I addressed the question of heterogeneity of the input pattern to the VMH neurons and the relationship between the VMH activity and the behavioural output. Taken all together, the results of this project have led to a hypothesis whereby the function of the VMH is to facilitate rather than directly control the choice of an appropriate behavioural response.
ventromedial hypothalamus, defensive behaviour, innate behaviour, calcium imaging, electrophysiology, optogenetics, whole cell patch clamp, medial amygdala, VMH, SF1+, olfactory stimuli, auditory stimuli, ultrasound
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