The human brain contains over 100 billion neurons (there are over 100 million in the mouse brain), yet memories are thought to be stored in only small groups of them. Identifying the precise neurons encoding a given memory has been a longstanding challenge. In the past, scientists had deleted an entire brain region in mice to try and erase a memory in the hopes of finding out about how memories are normally stored, but in this study led by Sheena Josselyn, Assistant Professor of Physiology, Canada Research Chair in Molecular and Cellular Cognition and a SickKids scientist, researchers took a more targeted approach and removed only the small portion of neurons thought to be involved in a specific memory.
"Though previous studies have provided important evidence suggesting that specific neurons are involved in a memory, we believe this paper is the first to establish causal links," said Josselyn.
In a previous paper, the research team showed evidence suggesting that in mice, fear memories are stored in specific neurons within a brain structure known as the lateral amygdala (LA) that have a high amount of a specific protein (CREB). This means that CREB levels helps dictate which neurons are involved in storing a memory. In the latest study, the scientists went on to destroy only these LA neurons with high levels of CREB and found that mice no longer remembered the fearful event. More importantly, they illustrated that random removal of a similar number of LA neurons does not impact the fear memory. These findings are the first to definitively show which specific set of neurons store a memory.
"Our experiences, both good and bad, teach us things," said Josselyn. "If we didn't remember that the last time we touched a hot stove we got burned, we would be more likely to do it again. So in this sense, even memories of bad or frightening experiences are useful. However, there are some cases in which fearful memories become maladaptive, such as with post-traumatic stress disorder or severe phobia. Selectively erasing these intrusive memories may improve the lives of afflicted individuals," she said.
"Do our results suggest that someday this might be possible? Our studies suggest that one strategy would be to target interventions to that small subset of neurons actually involved in storing a memory, rather than the entire brain. It sounds like a futuristic film, but our results in mice do provide proof-of-principle that this may one day be possible in humans," added Paul Frankland, SickKids Scientist, Assistant Professor of Physiology, Canada Research Chair in Cognitive Neurobiology and co-investigator of the study.
"Our memories are an essential part of who we are, in fact some believe it is the ongoing connection between our thoughts and memories that constitutes our identity," said Christine Harrison, SickKids Director of Bioethics. "As the research in this area continues to evolve, so do the ethical considerations related to potential future therapies."
via [techno]
With the support of the National Institutes of Health, the Arnolds and their team have been able to take a piece of HIV that is involved with helping the virus enter cells, put it on the surface of a common cold virus, and then immunize animals with it. They found that the animals made antibodies that can stop an unusually diverse set of HIV isolates or varieties.
Some researchers have previously been able to elicit effective antibodies, but usually only against a very limited number of HIV types. With HIV’s known propensity to mutate, antibodies developed against one local strain may not recognize and combat mutant varieties elsewhere. These geographic varieties with different mutations constitute one of the great challenges to finding a broad spectrum vaccine capable of protecting against the vast array of HIV varieties.
Human rhinovirus showing pieces of HIV (red) that stimulate helpful immune responses displayed on the rhinovirus surface, thereby creating a safe mimic of HIV. Credit: Gail Ferstandig Arnold
“The part that we targeted plays a role in the ability of HIV to enter cells, and is common to most HIV varieties,” Gail Ferstandig Arnold said. “That is a mechanism that would not be easy for the virus to reinvent on the fly, so it turns out to be a really helpful target.”
The Arnolds are both members of the Center for Advanced Biotechnology and Medicine, a joint center of Rutgers, The State University of New Jersey, and the University of Medicine and Dentistry of New Jersey. Also, Gail Ferstandig Arnold is a research professor and Eddy Arnold is a professor, both in Rutgers’ Department of Chemistry and Chemical Biology.
“The idea is to trick the immune system into thinking it is acting upon HIV before the virus shows actually shows up on the scene,” said Eddy Arnold.
To actually accomplish this is a big problem in engineering. The goal was to take a small piece of the HIV out of its native context, put it in a completely different system (rhinovirus), and have it look the same and act the same. Eddy Arnold likens this to taking the Rocky Mountains, putting them on India and having them look exactly right.
Using recombinant engineering, the research team developed a method to systematically test millions of varied presentations of the HIV segment with the rhinovirus. They tried millions of different variations on how to graft (or splice) one onto the other, creating what are called combinatorial libraries.
“It’s like the lottery,” Eddy Arnold commented. “The more tickets you buy the better chance you have of winning.”
“The really exciting part is that we were able to find viruses that could elicit antibodies against a huge variety of isolates of HIV. That is an immense step and a very important step,” said Gail Ferstandig Arnold.
“However, we need to be careful to not overstate things because the quantity of response is not huge, but it is significant,” added Eddy Arnold. “This is actually the first demonstration of this particular Achilles heel being presented in way to generate a relevant immune response. It is probably not potent enough by itself to be the vaccine or a vaccine, but it is a proof of principle that what we are trying to do is a very sound idea.”
via [techno]