Molecular steps in memory consolidation are associated with susceptibility to disruption by external novel stimuli
The question of how short-lived memories (~the momentary contents of one’s consciousness) become stored in long-term memory that lasts up to one’s lifetime is one of the most fundamental ones in cognitive neuroscience. This process is referred to as memory consolidation. While the underlying neural mechanisms have begun to be understood with increasing detail, open questions have remained. As one instance of this, there is research indicating that memory consolidation is not a unitary one-step process, but rather that there are lapses in memory even after the initial consolidation.
Thriving on recent advances in understanding the behavioral and molecular mechanisms underlying memory consolidation in Lymnaea during associative conditioning, Marra et al. (2012) studied the neural events underlying lapses in memory that take place during consolidation. Using a specific in vitro behavioral one-trial conditioning approach, the authors observed lapses in memory at 30 min and 2 hours after conditioning, but not at other tested time points of 10 min, one, three, and four hours. While the lapse at 30 min marked transition from short-term to intermediate-term memory, the lapse at two hours post-conditioning suggested that intermediate-term memory has early and late phases with distinct underlying molecular mechanisms. Furthre, these lapses constituted time points during which memory consolidation was susceptible to disruption by external stimuli. Disruption at two hours blocked long-term memory 24 hours later, and disruption at 30 min blocked recall at three and four hours post-conditioning. The underlying molecular mechanisms were studied by inspecting the effects of specific pharmacological agents modulating protein kinase activity on these different phases of consolidation.
The results suggested specific steps in memory consolidation, with changes in properties of ion channels resulting in increased excitability lasting for at least 10 min post-training, followed by enhancement of synaptic efficacy by proteins synthesized from existing RNA between 10 min and the first hour (e.g., insertion of more channel proteins) that lasts up to three hours. New synapses are then produced over at least the first 24 hours that correspond to consolidation to long-term memory. The long-term memory consolidation was observed to be dependent on protein kinases C and M, with early and late phases of long-term memory however differing in requirement of for duration of protein kinase A activity after training. Taken together, these results are highly exciting in illuminating specific molecular events underlying the distinct steps that lead to consolidation of memories from short-term through intermediate-term to long-term memory, and by showing how the transition periods between the processes of consolidation are specifically susceptible to disruption by distracting stimuli/events.
Reference: Marra V, O’Shea M, Benjamin PR, Kemenes I. Susceptibility of memory consolidation during lapses in recall. Nature Communications (2013) 4: 1578. http://dx.doi.org/10.1038/ncomms2591