Grant: Travel Awards - Institute Community Support

The ability to identify environments as either threatening or safe is crucial for survival and relies on our integration of past experiences with current situations to guide appropriate behaviour. Individuals with post-traumatic stress disorder (PTSD) often struggle with this process, generalizing their fear responses even in safe environments. Importantly, PTSD is 2-3 times more prevalent in women, therefore, it is vital to understand sex differences in the neural mechanisms that guide this behaviour to develop effective treatments. One area of the brain that plays a key role in managing fear responses is the medial prefrontal cortex (mPFC). This region is involved in decision-making and its neural representation changes when the meaning of an environment is altered. Interestingly, dopamine, a neurotransmitter usually associated with motivation and reward, has also been linked to fear learning in the mPFC and there are sex differences observed in the expression of dopamine receptors in this region. To investigate sex differences in mPFC dopamine signalling during expression of fear behaviour in different environments, we "teleported" male and female mice between environments with different threat levels while monitoring dopamine signalling in real-time. We found that males but not females showed increased mPFC dopamine signalling during teleportation when the contexts had different threat levels. However, inhibiting mPFC dopamine affected females more than males in their ability to discriminate between the environments. Our findings aim to enhance our understanding of sex differences in fear processing in the brain and ultimately guide the development of innovative therapeutic interventions for individuals with PTSD.