Memory Enhancement Achieved in Rats

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Memories are fragile; initially forming and then retrieving them are both dependent on new protein synthesis in the brain, and both processes are vulnerable to disruption. A number of agents are known that can impair memory and these can certainly be useful — for example, in treating post-traumatic stress disorder (ptsd). Enhancing memory, however, has proven more difficult. Yet as noted in The New York Times last week [1], two different research groups have recently reported enhancing memory in rats [2-3]. Of note is the fact that they did so utilizing independent molecular pathways.

The first study appeared in the journal Nature and describes work performed by scientists in New York and Spain. Their work focuses on insulin-like growth factor II (IGF2), the most abundant of the insulin-like growth factors found in the brain. Its expression in the brain begins during embryonic development, is maintained throughout adulthood and declines with age. Expression of IGF2 is also known to be induced after learning, suggesting that it plays a role in memory consolidation. The scientists showed that injecting IGF2 into the hippocampus of rats within fifteen minutes after inhibitory avoidance training ”significantly and persistently enhanced memory retention at 24 hours and 7 days,” and that this memory enhancement was retained when the rats were tested three weeks later; they deduced from this latter finding that IGF2 also prevents forgetting. The researchers then went on to demonstrate that IGF2 facilitates long-term potentiation in the hippocampus; long-term potentiation is a cellular process thought to correlate with the formation of long-term memories.

The second study, published in the journal Science a week later, was performed by a group of Israeli researchers at the Weizmann Institute of Science. They found that infusing a particular enzyme, protein kinase C, zeta form (PRKCZ), into the insular cortex of rat brains enhanced the rats’ long-term memories of a conditioned taste aversion. This effect was observed when the enzyme was administered before memory formation but, importantly, it was also seen when the enzyme was given a week afterwards, once the memory has been consolidated and is considered to be long-term. The researchers chose to focus on this particular enzyme because they had previously demonstrated that inhibiting it erases long-term memories in rats [4]. They also ascertained that the enzyme worked not by preventing the normal course of memory fading but rather by enhancing the memory once it had already faded, and that it could enhance two different memories acquired at different times, and not only the most recently acquired memory.

These two proteins — IGF2 and PRKCZ — may serve as new targets for memory enhancement therapies. Such therapies would be beneficial in treating cognitive decline and amnesia.

References

1. A Deep Dive to Retrieve and Fortify Memories. The New York Times. 2011 Mar 7.
2. Chen et al. A critical role for IGF-II in memory consolidation and enhancement. Nature. 2011 Jan 27;469(7331):491-7.
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3. Shema et al. Enhancement of consolidated long-term memory by overexpression of protein kinase Mzeta in the neocortex. Science. 2011 Mar 4;331(6021):1207-10.
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4. Shema et al. Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKM zeta. Science. 2007 Aug 17;317(5840):951-3.
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