While the hippocampus may play an essential role in the expression of memories soon after training, over time these memories are thought to become increasingly dependent on coordinated activity in a broad network of cortical and subcortical brain regions. However, the distributed nature of this representation has made it challenging to define the neural elements of the memory trace, and lesion and electrophysiological approaches provide only a narrow window into what is appreciated to be a much more global network. Here global mapping approaches are used to identify networks of brain regions that are activated and co-activated following recall of recent and remote contextual fear memory in mice. Analysis of Fos expression across 84 brain regions allowed for the description of brain-wide activity and interactivity of brain regions associated with memory expression. Activity analysis revealed that remote memory engages a broad collection of cortical and subcortical regions in comparison to recent memory expression. Interactivity analyses revealed that functional connectivity associated with fear memories depends on memory age and is altered in mutant mice that exhibit premature forgetting. In-depth functional connectivity analysis of remote long-term fear memory indicates that memory recall engages a network that has a distinct thalamic-hippocampal-cortical signature. This network is concurrently integrated and segregated and therefore has small-world properties as well as a resilient core of highly inter-connected regions. Centrality measures identify a collection of regions that may play a critical role in the function of the network including expected regions such as the anterior cingulate cortex and prelimbic cortex as well as novel regions including the reuniens thalamic nucleus. Post conditioning lesions of the reuniens lead to mild deficits in contextual fear memory expression providing support for the idea that identified hub regions may play a critical role in the function of the network. These results identify and describe functional activity and interactivity of brain regions underlying recent and remote fear memory expression and provide strong evidence for reorganization and distribution of the functional organization of memories over time.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32850 |
| Date | 31 August 2012 |
| Creators | Wheeler, Anne |
| Contributors | Frankland, Paul |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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