Lock - in Enzyme for Memories

Again we are getting closer tounderstanding a clear empirical phenomenon. That short and long term memories operate very differently from personto person with no real rhyme nor reason.

This suggests that enzymemodification can by effective and plausibly beneficial and perhaps we willsomeday polish an exam preparation with a series of drinks over a couple ofdays.

Now we are much closer to understandingit at the least.

Molecule that can erase or restore long-term memories – in rats

22:35 March 7, 2011

A neuron in a rat brain's cortex over-expressing PKMzeta shown in blue(Image: Todd

If you're struggling to remember the names of classmates from highschool, or just can't forget that time you made a complete ass of yourself infront of your high school crush, then a single molecule known as PKMzeta couldbe to blame – and increasing or decreasing its activity in the brain couldeither help you remember those names that seem on the tip of your tongue ordrive that embarrassing memory from your head. In a new study, researchers havedemonstrated that a memory in rats can either be enhanced or erased long afterit is formed by manipulating the activity of the brain enzyme PKMzeta.

In earlier studies, the researchers conditioned rats to associate anauseating sensation with saccharin by pairing it with lithium, so that theyshunned the sweet taste. However, after the rats received a chemical thatblocked the enzyme PKMzeta in the brain's neocortex, where long-term memoriesare stored, their sweet tooth returned within a couple of hours. The effectonly worked retroactively and appeared to be permanent, suggesting that PKMzetamay be required for sustaining memories throughout the brain.

To confirm the findings of these earlier studies and to demonstrate theopposite effect, the researchers carried out a new study funded by the NationalInstitutes of Health (NIH) using the same aversive learning model and paired itwith genetic engineering to increase PKMzeta. To produce an overexpression ofthe enzyme, they harnessed a virus to infect the neocortex with the PKMzetagene and saw an enhancement in the rats' memory function.

Conversely, replacing the naturally occurring PKMzeta with a mutantinactive form of the enzyme, erased the memory in much the same way as thechemical blocker used in the previous studies did.

"One explanation of the memory enhancement is that PKMzeta mightgo to some synapses, or connections between brain cells, and not others,"said Todd Sacktor, of the SUNY Downstate Medical Center, New York City, agrantee of the NIH's National Institute of Mental Health (NIMH)."Overexpressed PKMzeta may be selectively captured by molecular tags thatmark just those brain connections where it's needed – likely synapses that wereholding the memory from the training."

Earlier this year, another study funded by the National Institute ofHealth found that treating rats with a insulin-like growth factor (IGF-II)significantly boosted retention and prevented forgetting of a fear memory aslong as the naturally occurring growth factor was injected into the rats'memory circuitry during time-limited windows just after learning and uponretrieval, when memories become fragile and changeable.

In contrast, the researchers say the PKMzeta mechanism appears to workanytime and the effects applied generally to multiple memories stored in thetarget brain area, which raises questions about how specific memories might betargeted in any future therapeutic applications.

"This pivotal mechanism could become a target for treatments tohelp manage debilitating emotional memories in anxiety disorders and forenhancing faltering memories in disorders of aging," said NIMH Director ThomasR. Insel, M.D.

A paper detailing the findings of the study are published in thejournal Science.

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