Summary: A new study finds that the brain actively blocks the formation of new long-term memories immediately after waking, using a protein synthesis–dependent mechanism that protects memory consolidation carried out during sleep.
Source: Bar-Ilan University
Bar-Ilan University researchers reveal that a protein synthesis–dependent process prevents new learning on waking, protecting the ongoing consolidation of memories formed during sleep.
Every day we experience a continuous stream of events and stimuli. Some of these events trigger changes in neuronal connections and initiate the formation of memory traces. These early traces are fragile: only a subset will stabilize and become long-term memories that can last for years. The stabilization process, known as memory consolidation, strengthens these fragile traces so they persist beyond the immediate period after learning.
Let’s sleep on it
Consolidation relies on the production of new proteins that reinforce nascent memory traces. Because new experiences arriving while consolidation is underway could disrupt or hijack the process, the brain minimizes interference by shifting much of the consolidation to sleep, a period when external inputs are reduced. This raises an important question: if someone wakes during consolidation, how does the brain prevent new stimuli at that moment from interrupting the stabilization of existing memories?
Researchers led by Prof. Abraham Susswein of the Mina and Everard Goodman Faculty of Life Sciences and The Leslie and Susan Gonda Multidisciplinary Brain Research Center at Bar-Ilan University investigated this question. The study, with Roi Levy as first author and including part of David Levitan’s doctoral work, was published in eLife. Their experiments used the marine mollusk Aplysia, which is well suited for neuroscience research because of its relatively simple nervous system, large identifiable neurons, and capacity for basic learning.
Just after training during wakefulness, the nervous system synthesizes proteins that initiate memory consolidation. During sleep, consolidation-related protein production increases again to support further strengthening of the memory trace. The team found that blocking protein synthesis in sleeping Aplysia prevented formation of long-term memories, demonstrating that these animals consolidate memories during sleep much like mammals do.
Overcoming memory blocking
The study shows that when Aplysia were exposed to new stimuli immediately after waking, these experiences did not produce new long-term memories. In a learning paradigm that modifies feeding behavior, animals trained on awakening failed to form long-term memories from those new experiences. This indicates an active process on waking that blocks the formation of new long-term memory and thereby prevents interference with consolidation occurring during sleep.
Crucially, when the researchers administered a protein synthesis inhibitor to the animals just before training on awakening, this block was removed: the previously ineffective post-waking stimuli generated long-term memory. These results suggest that specific proteins expressed at waking actively prevent encoding of new long-term memories. Inhibiting protein synthesis eliminates that inhibition, allowing even very brief experiences to be incorporated into long-term memory immediately after waking—experiences that would not form lasting memories in fully awake animals under normal conditions.
Susswein explains: “The major insight from this research is that there is an active process in the brain that inhibits the ability to learn new things on waking and thereby protects the consolidation of memories.”
Two heads are better than one
The team also compared learning in fully awake Aplysia trained in social isolation with those trained in the presence of companions. Training in social isolation dampened new learning, and the molecular signatures underlying this isolation-induced reduction resembled those seen when animals were trained immediately after waking. In other words, similar protein-dependent processes appear to block new memory formation both on waking and during socially isolated conditions.
For the future
Next steps include identifying the specific proteins responsible for the post-waking memory block and determining the molecular mechanisms by which they inhibit new memory formation. Understanding these targets could also shed light on why people typically do not remember dreams upon waking. Finally, the researchers note the therapeutic potential: if similar blocking proteins exist in humans, they might be harnessed or modulated to prevent or weaken unwanted memories, for example in post-traumatic stress disorder (PTSD).
Funding: This research was funded by the Israel Science Foundation (ISF).
Source: Elana Oberlander, Bar-Ilan University
Original research: Roi Levy, David Levitan, and Abraham J. Susswein, “New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process,” eLife, published online December 5, 2016. DOI: 10.7554/eLife.17769.
New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process
Brief experiences while a memory is being consolidated may either capture the consolidation process and produce a maladaptive memory or interrupt consolidation altogether. Because consolidation occurs during sleep, even brief experiences when animals are awakened could have such effects. In Aplysia feeding paradigms, training after awakening did not produce long-term memory because a block prevented new learning. Inhibiting protein synthesis removed the block and allowed even brief, normally ineffective training to produce long-term memory. Formation of these memories relied on consolidative proteins already expressed before training; after effective training, subsequent transcription and translation were required for long-term memory. Memory formation during the sleep phase correlated with increased CREB1 transcription but not CREB2 transcription. Increased C/EBP transcription correlated with both effective and ineffective training and treatments that did not produce memory.