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This is an archive article published on March 29, 2013

Brain8217;s 8216;molecular memory switch8217; identified

Research reveals a new target to reverse the devastating effects of memory loss

Scientists have identified a key molecule responsible for triggering the chemical processes in the brain linked to formation of memories.

The research,led by scientists at the University of Bristol,reveals a new target for therapeutic interventions to reverse the devastating effects of memory loss.

Previous studies have shown that our ability to learn and form memories is due to an increase in synaptic communication called Long Term Potentiation LTP.

This communication is initiated through a chemical process triggered by calcium entering brain cells and activating a key enzyme called 8216;Ca2 responsive kinase8217; CaMKII.

Once this protein is activated by calcium it triggers a switch in its own activity enabling it to remain active even after the calcium has gone. This special ability of CaMKII to maintain its own activity has been termed 8216;the molecular memory switch8217;.

Until now,the question still remained as to what triggers this chemical process in our brain that allows us to learn and form long-term memories.

The research team,comprising scientists from the University8217;s School of Physiology and Pharmacology,conducted experiments using the common fruit fly Drosophila to analyse and identify the molecular mechanisms behind this switch.

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Using advanced molecular genetic techniques that allowed them to temporarily inhibit the flies8217; memory the team were able to identify a gene called CASK as the synaptic molecule regulating this 8216;memory switch8217;.

8220;In experiments whereby we tested the flies8217; learning and memory ability,involving two odours presented to the flies with one associated with a mild shock,we found that around 90 per cent were able to learn the correct choice remembering to

avoid the odour associated with the shock,8221; said Dr James Hodge,the study8217;s lead author.

8220;Five lessons of the odour with punishment made the fly remember to avoid that odour for between 24 hours and a week,which is a long time for an insect that only lives a couple of months,8221; Hodge said.

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By localising the function of the key molecules CASK and CaMKII to the flies8217; 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 wasn8217;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. The study was published in the journal Frontiers in Neural Circuits.

 

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