Propofol modulates early memory consolidation in humans

Abstract

Maintenance of memory across time is crucial for adaptive behavior. Current theories posit that the underlying consolidation process depends on stabilization of synapses and reorganization of interactions between hippocampus and neocortex. However, the temporal properties of hippocampal-neocortical network reconfiguration during consolidation are still a matter of debate. Translational research on this issue is challenged by the paucity of techniques to transiently interfere with memory in the healthy human brain. Here, we report a neuro-pharmacological approach with the GABA_A-ergic anesthetic propofol and a memory task sensitive to hippocampal dysfunction. Patients undergoing minor surgery learned word lists before injection of an anesthetic dose of propofol. Results show that administration of the drug shortly after learning (∼13 min) impairs recall after awakening but spares recognition. By contrast, later administration (∼105 min) has no effect. These findings suggest significant changes in memory networks very early after learning that are decisive for later recall. Propofol general anesthesia provides an experimental tool to modulate the first steps of hippocampus-mediated memory consolidation in humans.

Significance statement Consolidation of memories depends both on mechanisms at the synaptic and the systems level. How and when these mechanisms interact is currently unclear. Here, we have used the anesthetic drug propofol to create a transient pharmacological ‘lesion’ of the neural substrates of memory consolidation in humans undergoing minor surgery. Our results show that there is a brief time window after learning where hippocampus-dependent memories are susceptible to GABA-ergic modulation with propofol. Later recall appears to depend significantly on integrity of these first steps of memory formation. We infer that there is significant rearrangement of memory networks during the first hours after learning. Propofol general anesthesia provides an experimental approach to interfere with early memory consolidation in humans.