Aller au contenuAller au menuAller à la recherche

Oliver Hardt et Virginia Migues"The neurobiology of memory persistence and forgetting: Regulation of the synaptic content of GluA2-containing AMPA receptors mediates persistence and decay of long-term memory."

Abstract :


While much has been learned about how memories are encoded, formed, and initially stored, very little is known about how they can persist over long time periods, and how they are eventually forgotten.
We have found that the persistence of long-term memory requires the maintenance of a steady-state level of synaptic GluA2-containing AMPA receptors (GluA2-AMPARs). Long-term memory strength positively correlates with the level of GluA2-AMPAR post-synaptic expression. 

Consequently, disrupting the synaptic stability of GluA2-AMPARs by blocking the activity of PKMzeta or by directly interfering with the binding of the protein NSF and GluA2 leads to memory erasure. 
Importantly, blocking GluA2-AMPAR internalization can prevent this effect. In light of this, we tested whether removal of post-synaptic GluA2-AMPARs underpins forgetting, and found that blocking GluA2-AMPAR internalization in the dorsal hippocampus prevented forgetting of long-term object location memory in rats.

The same treatment potentiated new subsequent location learning rather than impairing it, contrary to the predictions of interference views of forgetting. Furthermore, we found that blocking GluN2b-NMDARs during the retention interval also prevented forgetting, while activation of GluN2b-NMDARs accelerated forgetting. These findings thus identify the neurobiological substrate of a decay-like forgetting process in the hippocampus. Involving activation of GluN2b-NMDARs, this process removes synaptic GluA2-AMPARs, thereby systematically eliminating consolidated memories over time. 

These findings supports an emerging conceptual understanding of memory in which the persistence of long-term memories depends on a set of dynamic processes that counteract a constitutive process of forgetting.

Selected publications

Migues P. V., Hardt O., Wu D. C., Gamache K., Sacktor T. C., Wang Y. T. & Nader K. (2010). PKMzeta maintains memories by regulating GluR2-dependent AMPA receptor trafficking. Nature Neuroscience, 13(5), 630–634.

Hardt O., Migues P. V., Hastings M., Wong J. & Nader K. (2010). PKMzeta maintains 1-day- and 6-day-old long-term object location but not object identity memory in dorsal hippocampus. Hippocampus, 20(6), 691–695.

Hardt O., Einarsson E. Ö. & Nader K. (2010). A bridge over troubled water: reconsolidation as a link between cognitive and neuroscientific memory research traditions. Annual review of psychology, 61, 141–167.

Nader K. & Hardt O (2009). A single standard for memory: the case of reconsolidation. Nature Reviews Neuroscience, 10(3): 224-234.

Hardt O., Wang S. H. & Nader K. (2009). Storage or retrieval deficit: The yin and yang of amnesia. Learning & Memory, 16(4), 224–230.

Guillaume Ferreira de NutriNeuro