Clues to Making and Breaking Memories Included in List of Year’s Top Science

January 30, 2007 • Science Update

NIMH-funded researchers were cited in Science Magazine’s December 2006 “Breakthrough of the Year” special issue. The most recent top 10 list of discoveries included major advances in understanding how memories are formed and stored, which may help scientists to develop treatments for many types of mental disorders.

Researchers had long suspected that creating memories relied on a process called long-term potentiation (LTP), a lasting increase in the connection strength between brain cells. LTP occurs in two phases, induction and maintenance, which may be compared to learning and remembering. LTP can be induced by electrically stimulating the brain, but proving that it occurs during learning has been far more difficult.

Improved methods to detect LTP-related changes in the brain recently allowed NIMH grantee Mark F. Bear, along with colleagues at the Massachusetts Institute of Technology (MIT), Brown University, and the Howard Hughes Medical Institute, to show for the first time that learning actually triggers LTP in the brain. The researchers compared rats that learned to avoid a dark chamber, where they had previously received a mild foot shock, with rats that either did not receive the shock or were taken out of the dark chamber right after the shock so they did not form the same fear memories. Looking at changes in the brains of rats from these different groups, the researchers showed that learning to avoid a fearful situation (in this case, entering the dark chamber) caused LTP to occur¹. This discovery may help scientists to better understand changes in the brain that lead to anxiety disorders in people and how these changes might be corrected.

In another study, researchers at the State University of New York Downstate Medical Center working with NIMH grantee Dr. Todd C. Sacktor greatly strengthened the case for LTP as a process for storing memories².Blocking PKMzeta, an enzyme needed for LTP maintenance, lead to a reversal of late-stage LTP, but did not affect early-stage LTP induction in rats. This resulted in selectively “erasing” day-old memories in the rats without affecting their ability to learn. Such findings may guide future research on possible treatments for disorders resulting from abnormal memory processes, such as post-traumatic stress disorder (PTSD), neuropathic pain, and epilepsy.

Other related articles listed by Science include:

• A. Gruart et al., “Involvement of the CA3-CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice,” J. Neurosci. 26, 1077 (2006)
• T.V.P. Bliss et al., “ZAP and ZIP, a Story to Forget,” Science 313, 1058 (2006). Perspective article highlighting the Whitlock et al. and Pastalcova et al. studies.
• T.V.P. Bliss and T. Lomo, “Long-Lasting Potentiation of Synaptic Transmission in the Dentate Area of the Anaesthetized Rabbit Following Stimulation of the Perforant Path,” J. Physiol., 232, 331 (1973) [PubMed Central]

References

Whitlock JR, Heynen AJ, Shuler MG, Bear MF. Learning induces long-term potentiation in the hippocampus . Science. 2006 Aug 25;313(5790):1093-7.

Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC. Storage of spatial information by the maintenance mechanism of LTP . Science. 2006 Aug 25;313(5790):1141-4.