Anxiety disorders cause considerable emotional distress and are frequently disabling, yet current therapies are inadequate. Understanding the molecular mechanisms underlying these disorders will be key in finding improved treatment. The Acid sensing ion channel 1 (ASIC1a) is a novel regulator of anxiety-like recently discovered in mice. The ASIC1a gene dose was found to significantly affect Pavlovian fear conditioning, an important animal model of anxiety. This finding suggests the hypothesis that ASIC1a plays a role in amygdala-dependent learning and memory. This hypothesis will be tested with the following aims: 1) Does pharmacologic inhibition of ASIC1a disrupt fear related learning or the expression of fear? 2) Does genetic disruption of ASIC1a restricted to the amygdala block normal fear related behavior? The proposed approach of combining pharmacologic and genetic strategies to target ASIC1a will provide the first steps for manipulating ASIC1a function in vivo. This will clarify its role in anxiety related behavior and could further elevate ASIC1a as a potential target for treatment of anxiety disorders in humans. ? ? ?
| Coryell, Matthew W; Wunsch, Amanda M; Haenfler, Jill M et al. (2009) Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior. J Neurosci 29:5381-8 |
| Coryell, Matthew W; Wunsch, Amanda M; Haenfler, Jill M et al. (2008) Restoring Acid-sensing ion channel-1a in the amygdala of knock-out mice rescues fear memory but not unconditioned fear responses. J Neurosci 28:13738-41 |
