Grant: Project Grant

Tackling fear behaviourally and in the brain holds the key to developing successful clinical interventions for fear and anxiety-related disorders. One way to do this is through exposure therapy, that is, exposure to fear-eliciting cues or triggers with the aim of decoupling them from fear. This approach has been successful for some but many relapse or fail to respond at all. The key to providing a better treatment to sufferers from anxiety is to look beyond the standard approach of targeting primary triggers for fear, that is, triggers have a direct association with a traumatic or aversive event. Our proposal does this. We will understand how fear spreads across a memory network, how it links with cues were never part of the original traumatic memory, thereby proliferating secondary triggers with fear. The present proposal will utilize a multifaceted approach to examine the behavioural and neural profile of secondary fear. Specifically, we will establish how secondary triggers lose their fear eliciting properties, and whether these properties can be restored under specific conditions. We will also examine whether secondary triggers depend on the original fear memory for retrieval by tackling the integrity of the original fear memory behaviourally (through extinction) and neutrally (through deletion of function-specific cells). Finally, we will uncover the neural circuits that support fear triggered by secondary cues. Our ultimate goal is to provide the basic science platform of fear triggered by secondary cues which will serve as a springboard for the development novel behavioural and pharmacological routes for the treatment of fear- and anxiety-related disorders.