| dc.description.abstract | Anxiety disorders are some of the most common and debilitating forms of mental illnesses in our society. Understanding the behavioral and brain mechanisms of anxiety is essential in the development of novel therapeutic interventions. One brain region that has emerged as an important regulator of anxiety in humans and other animals is the bed nucleus of the stria terminalis (BNST). However, the exact conditions under which the BNST is recruited to anxiogenesis is not known. Uncertainty with regards to when negative events will occur is thought to be factor in the development of anxiety. Accordingly, the purpose of this study was to test the contributions of the BNST in an animal model of aversive learning using two different types of stimuli: one that is highly predictive of the onset of an aversive event, and one that is not. We hypothesized that plasticity in the BNST is required for learning about the ambiguous threat, but not when the stimulus is predictable. To do so, we performed intracranial microinfusions of APV (a drug that blocks plasticity in neurons, which is required for learning) in male and female rats prior to training to the stimuli; rats were subsequently tested to the stimuli off-drug. Our results revealed that plasticity in the BNST is essential for learning about temporally uncertain stimuli, but not when the cues are highly predictive. These data indicate that timing of aversive events regulates the BNST’s contributions to anxiety, such that when the subject is uncertain of when a negative event is going to happen, the BNST is necessary. These finding have important implications for future anxiolytic therapies of fear- and anxiety-related disorders (including posttraumatic stress disorder, PTSD) that target the BNST. | en |
