Anxiety disorders, such as PSTD, are characterized by generalization of fear responses to neutral stimuli. We have been examining the mechanisms of fear generalization using context fear conditioning, which involves pairing a context with several foot shocks that elicits fear responses (e.g. freezing) to that context. We have previously identified that GABAB(1a) receptors play an important role in maintaining memory precision for context. GABAB(1a)-/- mice show generalized fear to a neutral context 24 hours after training, but not 2 or 6 hours after training (Cullen, et al. 2014). To examine more precisely if GABAB(1a) receptors are involved in consolidation or retrieval of a precise fear memory, we administered central infusions of the selective GABAB(1a) receptor antagonist, CGP 36216, 30 minutes before training, immediately after training, or 30 minutes before a retrieval test in either the training context or a neutral context. Pre-training infusions resulted in fear generalization to the neutral context at 24 hours and 48 hours, but not 6 hours after training. Infusing after training or 30 minutes before the 24 hour retention test also resulted in fear generalization to the neutral context. These data suggest that GABAB(1a)-mediated presynaptic inhibition during consolidation and retrieval help preserve context memory precision. We have identified the time frame and the effective dose of CGP 36216, and will now determine the circuitry involved to induce fear generalization.
Dr. Aaron M. Jasnow
Mr. Joseph F. Lynch III