Enzyme Enhances, Erases Long-Term Memories in Rats
Posted Mar 03 2011 7:23pm
Even long after it is formed, a memory in rats can be enhanced or erased
by increasing or decreasing the activity of a brain enzyme, say researchers
supported, in part, by the National Institutes of Health.
"Our study is the first to demonstrate that, in the context of
a functioning brain in a behaving animal, a single molecule, PKMzeta,
is both necessary and sufficient for maintaining long-term memory," explained
Todd Sacktor, of the SUNY Downstate Medical Center, New York City, a
grantee of the NIHs National Institute of Mental Health.
Sacktor, Yadin Dudai, Ph.D., of the Weizmann Institute of Science, Rehovot,
Israel, and colleagues, report of their discovery March 4, 2011 in the
"This pivotal mechanism could become a target for treatments to
help manage debilitating emotional memories in anxiety disorders and
for enhancing faltering memories in disorders of aging," said NIMH
Director Thomas R. Insel, M.D.
In the new study, they paired genetic engineering with the same aversive
learning model to both confirm the earlier studies and to demonstrate,
by increasing PKMzeta, the opposite effect. They harnessed a virus to
infect the neocortex with the PKMzeta gene, resulting in overexpression
of the enzyme and memory enhancement. Conversely, introducing a mutant
inactive form of the enzyme, that replaced the naturally occurring one,
erased the memory — much as the chemical blocker did.
These effects applied generally to multiple memories stored in the targeted
brain area raising questions about how specific memories might be targeted
in any future therapeutic application.
The researchers turned up a clue that may hold the beginning of an answer.
The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website ( http://www.nimh.nih.gov/ ).
The National Institutes of Health (NIH) — The Nation's Medical
Research Agency — includes 27 Institutes and Centers and is
a component of the U.S. Department of Health and Human Services. It is
the primary federal agency for conducting and supporting basic, clinical
and translational medical research, and it investigates the causes, treatments,
and cures for both common and rare diseases. For more information about
NIH and its programs, visit www.nih.gov .
Shema R, Haramati S, Ron S, Hazvi S, Chen
A, Sacktor TC, Dudai Y. Enhancement of consolidated long-term memory by
overexpression of protein kinase Mzeta in the neocortex. 03/2/2011, Science.
How does PKMzeta maintain long-term memory? Sacktor TC. Nat Rev Neurosci.
2011 Jan;12(1):9-15. Epub 2010 Dec 1. Review. PMID:21119699
A neuron in a rat brains cortex over-expressing
PKMzeta (blue). Source: Todd Sacktor, M.D., SUNY Downstate Medical
Close-up of a neuronal extension, revealing
that PKMzeta (yellow/red) appears to be selectively recruited only
to certain brain connections, where its likely needed to help support
memories. Source: Todd Sacktor, M.D., SUNY Downstate Medical