Posted on 09/17/2010 2:05:52 PM PDT by decimon
Deleting a certain gene in mice can make them smarter by unlocking a mysterious region of the brain considered to be relatively inflexible, scientists at Emory University School of Medicine have found.
Mice with a disabled RGS14 gene are able to remember objects they'd explored and learn to navigate mazes better than regular mice, suggesting that RGS14's presence limits some forms of learning and memory.
The results were published online this week in the Early Edition of the Proceedings of the National Academy of Sciences.
Since RGS14 appears to hold mice back mentally, John Hepler, PhD, professor of pharmacology at Emory University School of Medicine, says he and his colleagues have been jokingly calling it the "Homer Simpson gene."
RGS14 is primarily turned on in one particular part -- called CA2 -- of the hippocampus, a region of the brain known for decades to be involved in consolidating new learning and forming new memories. However, the CA2 region lies off the beaten path scientifically and it's not clear what its functions are, Hepler says.
RGS14, which is also found in humans, was identified more than a decade ago. Hepler and his colleagues have previously shown that the RGS14 protein can regulate several molecules involved in processing different types of signals in the brain that are known to be important for learning and memory. They believe RGS14 is a key control protein for these signals.
To probe RGS14's functions, Sarah Emerson Lee, a graduate student working with Hepler, characterized mice whose RGS14 genes were disabled using gene-targeting technology. In collaboration with Serena Dudek, PhD, at the National Institute of Environmental Health Sciences, they examined how the CA2 region responded to electrical stimulation in the gene-altered mice.
Many researchers have examined how other parts of the hippocampus are involved in long-term potentiation, a strengthening of connections between neurons that can be seen after new memory formation or artificial stimulation in a culture dish. The CA2 region is distinct from other regions for being resistant to long-term potentiation, and neurons within CA2 are able to survive injury by seizures or stroke more than neurons in other parts of the hippocampus.
The researchers were surprised to find that, in mice with a disabled RGS14 gene, the CA2 region was now capable of "robust" long-term potentiation, meaning that in response to electrical stimulation, neurons there had stronger connections. On top of that, the ability of the gene-altered mice to recognize objects previously placed in their cages was enhanced, compared to normal mice. They also learned more quickly to navigate through a water maze to a hidden escape platform by remembering visual cues.
"A big question this research raises is why would we, or mice, have a gene that makes us less smart – a Homer Simpson gene?" Hepler says. "I believe that we are not really seeing the full picture. RGS14 may be a key control gene in a part of the brain that, when missing or disabled, knocks brain signals important for learning and memory out of balance."
The lack of RGS14 doesn't seem to hurt the altered mice, but it is still possible that they have their brain functions changed in a way that researchers have not yet been able to spot. Besides being resistant to injury by seizure, certain types of CA2 neurons are lost in schizophrenia, and loss of another gene turned on primarily in the CA2 region leads to altered social behaviors, Hepler notes.
"This suggests that these mice may not forget things as easily as other mice, or perhaps they have altered social behavior or sensitivity to seizures," he says. "But not necessarily."
Lee is investigating some of these possibilities now.
"The pipe dream is that maybe you could find a compound that inhibits RGS14 or shuts it down," he adds. "Then, perhaps, you could enhance cognition."
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At Emory, collaborators included Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences, Yoland Smith, PhD, research professor of neurology (both at Yerkes National Primate Research Center), David Weinshenker, PhD, associate professor of human genetics and Yue Feng, PhD, associate professor of pharmacology, with additional contributions from J. David Sweatt, PhD, chair of neurobiology at University of Alabama, Birmingham.
The research was supported by the National Institutes of Health.
Reference:
S.E. Lee et al. RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. PNAS Early Edition (2010). http://www.pnas.org/content/early/2010/09/03/1005362107.abstract
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.
Cog ignition ping.
Perhaps it’s necessary for survival. If they were too intelligent, they might regret being mice.
Probably not a good thing to mess with this one.
“They’re loose, they’re organized, and they took my car keys.”
Realizing your function is to serve as food for other critters could be a real downer.
Mrs. Tell said, “That’s just what we need. Smart mice.”
But even if this gene limits memorization, that too may be a beneficial function.
A mouse without this gene may remember better, advantageous in mazes and experiments based upon logic, perhaps not so much so in the wild, where past experience is not always a sure guide to future expectations.
Imagine being a prisoner of your memory. “No! Cannot ask a girl out on a date, the last time I did that the gal said no, and that hurt! Never going to do THAT again!”
Genes limit them in RATS too. Look at the Kennedys, Cuomos and Reids.
I'm going to guess that it has something to do with politics.
“Pinky, I know what we are going to do tomorrow night....try to take over the world!!!”
Maybe the researchers should turn off RGS14 in their own brains, and then they will smart enough to figure out what it was for.
Same gene that causes liberalism.
“Same thing we do every night Pinky.... try to take over the world!!!!”
Ok, now we know what is wrong with lefties, they all have this itelligent suppressing gene in their brains.
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