We are all familiar with the unpleasant physical symptoms of stress – things like headache, irritability, and fatigue – which all stem from activity in our brain. The ability to respond to stress is an essential survival tool. However, when the stress system responds inappropriately, it can lead to mental health conditions such as depression and anxiety disorders.
How the brain reacts to stress, through changes to cells and circuits within the brain, remains for the most part a mystery. Our lab is working to understand how stressful situations can lead to long-term changes in brain circuitry and the functioning of individual brain cells, or neurons.
We focus on circuits in the paraventricular nucleus of the hypothalamus, which is the brain’s command-centre for stress responses. We explore how neurons in this area of the brain translate a stressful situation into an appropriate hormonal and behavioural response. One important element of how these neurons respond depends on the context of the stress.
For example, we have known, for some time, that repeated exposure to the same stressor changes your reaction to it over time. What we’ve discovered is that a single stress causes synaptic adaptations in the PVN. These adaptations may be critical for allowing the brain to filter out stressors that are not threatening.
In addition, the brain also has an amazing capacity to respond in a rapid way to unique stressors. So, while it may adapt over time to the same stress, it continues to remain vigilant to other perceived threats. We have discovered synaptic mechanisms that may explain how exposure to one stress may prime the brain to react more strongly to subsequent stressful events. This priming may become pathological and could be a root cause of hyper-responsiveness to stress that can have a significant impact on our health and well-being.
By understanding how stress leads to long-term changes in brain circuitry, we hope that we can learn how to “switch off” the brain’s inappropriate responses to unpredictable stress. It is the ever-present but unpredictable stress that many people face in their daily lives, that can send the brain’s stress responses into overdrive. Understanding how the brain’s stress command centre can discriminate between a repeated stress that is innocuous versus one that requires an immediate response is vital step towards the development of new ways of treating or preventing the disorders caused by stress.
What we are striving for is understanding the factors that create the balance between stress resilience and vulnerability. In order to survive and thrive, we must the ability to experience stress, respond appropriately, and then move on with our lives.