Contextual fear conditioning involves pairing a novel context (conditioned stimulus) with several footshocks (unconditioned stimulus) that serve to condition fear to that context. As the retention interval between training and testing increases context specificity is lost. In other words, the fear memory is no longer precise or context-specific, but has generalized to novel contexts at remote time points. In an attempt to investigate the neural pattern of an imprecise contextual memory trace as a function of time, we used fluorescent in situ hybridization to for Arc mRNA as a measure of neuronal activation following expression of a precise vs. imprecise context fear memory. Expression of a contextually precise memory involved increased Arc mRNA expression in both the dorsal and ventral CA1 regions of the hippocampus as well as the ACC and IL. Expression of a contextually imprecise fear memory involved Arc mRNA expression in the ventral CA1, ACC, IL, and the PL suggesting that both the hippocampus and prefrontal cortex are involved in the expression of a remote contextually imprecise memory. Further, inactivation of the ACC at remote time points returned the context memory to a precise state, but had no effect on memory for the training context. Taken together, these data suggest that as a context fear memory ages, both the hippocampus and prefrontal cortex interact in the expression of the memory trace resulting in the loss of precision. Preventing this interaction through inactivation of the ACC allows the hippocampus to express the contextually precise memory. In addition to the systems investigation of fear generalization, we also investigated a potential synaptic mechanism of the phenomenon. Specifically, we discovered that mice lacking a GABAB1 receptor subtype, GABAB1a, exhibit a loss of context discrimination compared to wild-type animals. Animals lacking GABAB1a receptors showed a significant, but not complete loss of context specificity 24 hours post-training. GABAB1a knock out mice exhibited a complete loss of context discrimination by 5 days post-training. However, knock out mice exhibited normal context discrimination immediately following training, suggesting that GABAB1A receptors are necessary for the retention, but not acquisition, of context discrimination. Our results indicate that presynaptic inhibition is required for the maintenance of context.
|Advisor:||Riccio, David, Jasnow, Aaron|
|Commitee:||Ciesla, Jeffrey, Fountain, Stephen, Johnson, John, Veney, Sean|
|School:||Kent State University|
|School Location:||United States -- Ohio|
|Source:||DAI-B 75/08(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Cognitive psychology, Physiological psychology|
|Keywords:||Context fear conditioning, Generalization, Memory precision, Presynaptic inhibition|
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