A Role for MEF2 in the Synaptic Plasticity Mechanisms Underlying Long-term Memory Formation

• Main Author: Cole, Christina Jean
• Other Authors: Josselyn, Sheena
• Language: en_ca
• Published: 2011
• Subjects: Memory; Synapse; MEF2; Behaviour; 0317; 0719
• Online Access: http://hdl.handle.net/1807/31686

The synaptic remodeling of neural circuits is thought to underly memory formation. Both long-term memory formation and remote memory formation are thought to involve a process restructuring of synapses in specific areas of the brain. The transcription factor myocyte enhancer factor 2 (MEF2) has been shown to restrict spine growth in both in vivo and in vitro. It has been suggested that MEF2 is a critical molecule involved in memory formation, however, MEF2‘s role in adult memory formation it is largely unexplored. Thus, we have sought to characterize MEF2’s involvement in the formation of long-term and remote memory formation. We first showed that acute overexpression of MEF2 in the hippocampus blocks long-term spatial memory formation and activity-dependent spine formation. We next found that acute overexpression of MEF2 in the lateral amygdala likewise blocks long-term fear memory formation, suggesting that MEF2 is critical protein involved in synaptic plasticity necessary for long-term memory formation. We next demonstrated the bi-directionality of MEF2 by decreasing MEF2 function in the hippocampus and amygdala and showing a facilitation in memory formation. Together, these results suggest that MEF2 is a critical protein, which regulates spine formation important for the formation of long-term memories. We next investigated whether similar synaptic plasticity mechanisms are involved in the systems consolidation. We acutely overexpressed MEF2 in the anterior cingulate cortex at different time points following contextual fear conditioning. We noted that there was a critical window, where MEF2 blocks spine density increases in the ACC and remote memory formation. Results from this study, suggest that cortical synapses undergo a process of strengthening and remodeling and that MEF2 is a critical regulator involved. Our results demonstrate that MEF2 is involved in the synaptic consolidation of long-term and remote memories.