Neural Mechanisms Involved in the Extinction of Long-Term Trauma
Post by Lina Teichmann
What's the science?
Traumatic experiences often result in enduring memories of fear. Exposure therapy is a common treatment to overcome trauma by exposing patients to the context of fear-inducing memories in a safe environment. However, it is known that exposure therapy is less successful if the traumatic experience occurred a long time ago. This week in Nature Neuroscience, Silva and colleagues used a fear extinction paradigm with mice to test how neural mechanisms involved in overcoming fear differ depending on the age of the traumatic memory.
How did they do it?
To mimic the trauma, the authors placed mice in a conditioning chamber, where they received electric shocks to their paws. After either 1 day or 30 days, the mice were re-exposed to the same chamber without receiving shocks (recall) with subsequent re-exposing events over several days (fear extinction). When the animals were re-exposed to the traumatic context, the fear response was behaviorally quantified by examining freezing responses (prolonged absences of motion). Viral tracing, neuronal activity mapping, fiber photometry, and chemo- and optogenetics were used to examine the effect of long-term fear extinction on neural circuitry. In particular, the authors examined the functional responses to long- and short-term fear extinction in infralimbic cortex to basolateral amygdala and thalamic nucleus reuniens to basolateral amygdala pathways.
What did they find?
To overcome trauma, fear-evoking contexts have to be newly associated with safety. The results show that the neural mechanisms underlying this type of fear extinction depend on whether the fear-evoking experience occurred recently or a long time ago. While direct connections from the infralimbic cortex to the basolateral amygdala are critical for recent fear extinction, long-term fear extinction requires the recruitment of an additional pathway. In particular, when overcoming long-term fear, fear-related information is sent upstream from the infralimbic cortex via the thalamic nucleus reuniens to the basolateral amygdala. The behavioral expression of fear – freezing – was modulated by the activity in the thalamic nucleus reuniens. The activity in the nucleus reuniens peaked just before the freezing response ended and the freezing length could be manipulated by artificially increasing or decreasing activity in this area. This finding suggests that activity in the thalamic nucleus reuniens plays a role in learning to associate safety with a context that initially evoked fear.
What's the impact?
Traumatic memories are often long-lasting and can lead to mental disorders such as post-traumatic stress disorder. Silva and colleagues show that the time that has passed since a fear-evoking event modulates neural mechanisms involved in overcoming trauma. These findings improve our understanding of long-lasting traumatic memories and set the stage for future research into how we can weaken traumatic associations.
Silva et al. A thalamo-amygdalar circuit underlying the extinction of remote fear memories. Nature Neuroscience (2021).Access the original scientific publication here.