Sears Lab

Fear and anxiety disorders involve brain systems that evolved for survival in life or death situations. These brain systems control ‘fight, flight or freeze’ behaviors, which are dysfunctional in psychiatric disorders such as PTSD (post-traumatic stress disorder) and various phobic disorders. For example, a car backfiring or a car honking may cause exaggerated behavioral and physiological responses in combat veterans suffering from PTSD.

In many cases, individuals suffering from fear and anxiety disorders withdraw from society, suffer from sleep disorders and depression, and may be driven to self-medicate with drugs of abuse.

In the lab we use a procedure referred to as Pavlovian threat conditioning (PTC) to create ‘emotional memories’ in rodents so we can study the brain molecules, cells and circuits that underlie responses to threat in health and disease.

Recently, we discovered that the activity of neurons in the hypothalamus, known collectively as the orexin (or hypocretin) system, is important for the formation of implicit memories about cues that warn of danger. We speculate that the orexin system may strongly influence normal reactions, as well as pathological overreactions, to environmental stimuli.

In the lab we are also interested in the brain and behavioral mechanisms underlying active responding (versus passive responses such as freezing) to threats. To study this, we use a Signaled Active Avoidance (SAA) behavioral paradigm in which animals can learn to avoid imminent threats.

We recently found that interactions between two key brain areas important for emotion and responses to emotional stimuli, the amygdala and the nucleus accumbens, respectively, are important for SAA. Moreover, we have also found the orexin system plays an integral role in motivating SAA behavior.

Understanding the brain mechanisms of coping, both passive and active, is the ultimate goal of our work. In the long term, we hope that this work will lead to better therapies for individuals suffering from anxiety and stress-related disorders.

Current Investigations

  • The Role of The Orexin System in Proactive Coping Behaviors: The orexin system controls many behaviors thought to underlie fear and anxiety disorders in humans. We are currently using advanced molecular, chemogenetic, optogenetic and behavioral techniques to characterize the orexin system’s role in coping with threats. We propose that molecular-genetic and neural activity of orexin neurons underlie individual differences in coping behaviors.
  • Neural Circuitry of Signaled Active Avoidance (SAA): In SAA, subjects respond during a signal that predicts threat in order to terminate the threat. Although passive avoidance can be maladaptive, SAA may involve neural circuitry that is similar to those necessary for adaptive coping. We are currently running SAA experiments in combination with chemogenetics and optogenetics to piece together the neural circuitry underlying adaptive versus maladaptive coping behaviors.