Scientists Identify Brain “Molecular Memory Switch”

Scientists have identified several molecules and mechanisms in the brain that act as ‘molecular memory switches’. These discoveries provide insights into how our brains form, store, and recall memories, and could potentially lead to new therapeutic interventions for memory loss and other cognitive disorders.

One key molecule identified is the Calcium/Calmodulin-dependent protein kinase II (CaMKII). This protein is activated by calcium entering brain cells, triggering a switch in its own activity, a process termed ‘the molecular memory switch’. The protein CASK was found to control this switch, playing a critical role in memory formation[1].

By localising the function of the key molecules CASK and CaMKII to the flies’ equivalent brain area to the human hippocampus, the team found that the flies lacking these genes showed disrupted memory formation. In repeat memory tests those lacking these key genes were shown to have no ability to remember at three hours (mid-term memory) and 24 hours (long-term memory) although their initial learning or short-term memory wasn’t affected. Finally, the team introduced a copy of the human CASK gene — it is 80 per cent identical to the fly CASK gene — into the genome of a fly that completely lacked its own CASK gene and was therefore not usually able to remember. The researchers found that flies which had a copy of the human CASK gene could remember like a normal wildtype fly. Dr Hodge, from the University’s School of Physiology and Pharmacology, said: “Research into memory is particularly important as it gives us our sense of identity, and deficits in learning and memory occur in many diseases, injuries and during aging”.

“CASK’s control of CaMKII ‘molecular memory switch’ is clearly a critical step in how memories are written into neurons in the brain. These findings not only pave the way for to developing new therapies which reverse the effects of memory loss but also prove the compatibility of Drosophila to model these diseases in the lab and screen for new drugs to treat these diseases. Furthermore, this work provides an important insight into how brains have evolved their huge capacity to acquire and store information.”

These findings clearly demonstrate that neuronal function of CASK is conserved between flies and human, validating the use of Drosophila to understand CASK function in both the healthy and diseased brain. Mutations in human CASK gene have been associated with neurological and cognitive defects including severe learning difficulties. [8]

Another study by neuroscientists at MIT discovered a molecular mechanism that allows memories to form through large-scale remodeling of cells’ chromatin. This remodeling, which occurs over several days, makes specific genes involved in storing memories more active[2].

A different study found a molecular “switch” in the brain that labels experiences as positive or negative. This switch was identified in the amygdala, a part of the brain involved in emotional processing[3].

Researchers have also revealed the structure of a critical receptor in the brain associated with learning, memory, behavior, and mood, known as the AMPA receptor. This receptor is activated by the neurotransmitter glutamate, forming permeable ion channels that carry signals between cells throughout the nervous system[4].

The signaling molecule Neuromedin U was found to play a crucial role in recalling negative memories in a study on roundworms. This molecule allows neurons to communicate with each other[5].

Finally, a study on Alzheimer’s disease in mice suggested that RNA editing can be used as a ‘molecular switch’ to prevent the breakdown of synapses, thereby rescuing memory[6].

These findings collectively provide a deeper understanding of the molecular mechanisms underlying memory formation and recall, and could potentially pave the way for new treatments for memory-related disorders.

Citations:

^{[1] https://www.sciencedaily.com/releases/2013/03/130328125226.htm
[2] https://news.mit.edu/2020/engram-memories-form-1005
[3] https://www.scientificamerican.com/article/newfound-brain-switch-labels-experiences-as-good-or-bad/
[4] https://news.ohsu.edu/2019/04/11/crucial-electrical-switch-in-brain-revealed-in-study-published-by-science
[5] https://neurosciencenews.com/negative-experience-learning-16282/
[6] https://www.scimex.org/newsfeed/broken-brain-connections-not-protein-clumps-may-lie-behind-alzheimers-study-in-mice-suggests
[7] https://www.brandeis.edu/now/2017/september/memory-molecule-CaMKII.html
[8] https://www.eurekalert.org/pub_releases/2013-03/uob-sib032813.php}