Gene Limits Learning and Memory in Mice
ScienceDaily (Sep. 19, 2010) — 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.
Researchers have found that deleting the RGS14 gene in mice can make them smarter by unlocking a mysterious region of the brain considered to be relatively inflexible. (Credit: iStockphoto)
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 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.
...
Read more here/Leia mais aqui: Science Daily
+++++
RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory
Sarah Emerson Lee a, Stephen B. Simons b, Scott A. Heldt c,d, Meilan Zhao b, Jason P. Schroeder e, Christopher P. Vellano a, D. Patrick Cowan a, Suneela Ramineni a, Cindee K. Yates a, Yue Feng a, Yoland Smith f,g, J. David Sweatt h, David Weinshenker e, Kerry J. Ressler c,d,f, Serena M. Dudek b, and John R. Hepler a,1
+Author Affiliations
Departments of aPharmacology,
cPsychiatry and Behavioral Sciences, and
eHuman Genetics,
dCenter for Behavioral Neuroscience,
fYerkes National Primate Research Center, and
gDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322;
bNational Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; and
hDepartment of Neurobiology, University of Alabama School of Medicine, Birmingham, AL 35294
Edited* by Lutz Birnbaumer, National Institute of Environmental Health Sciences, Research Triangle Park, NC, and approved August 17, 2010 (received for review April 19, 2010)
Abstract
Learning and memory have been closely linked to strengthening of synaptic connections between neurons (i.e., synaptic plasticity) within the dentate gyrus (DG)–CA3–CA1 trisynaptic circuit of the hippocampus. Conspicuously absent from this circuit is area CA2, an intervening hippocampal region that is poorly understood. Schaffer collateral synapses on CA2 neurons are distinct from those on other hippocampal neurons in that they exhibit a perplexing lack of synaptic long-term potentiation (LTP). Here we demonstrate that the signaling protein RGS14 is highly enriched in CA2 pyramidal neurons and plays a role in suppression of both synaptic plasticity at these synapses and hippocampal-based learning and memory. RGS14 is a scaffolding protein that integrates G protein and H-Ras/ERK/MAP kinase signaling pathways, thereby making it well positioned to suppress plasticity in CA2 neurons. Supporting this idea, deletion of exons 2–7 of the RGS14 gene yields mice that lack RGS14 (RGS14-KO) and now express robust LTP at glutamatergic synapses in CA2 neurons with no impact on synaptic plasticity in CA1 neurons. Treatment of RGS14-deficient CA2 neurons with a specific MEK inhibitor blocked this LTP, suggesting a role for ERK/MAP kinase signaling pathways in this process. When tested behaviorally, RGS14-KO mice exhibited marked enhancement in spatial learning and in object recognition memory compared with their wild-type littermates, but showed no differences in their performance on tests of nonhippocampal-dependent behaviors. These results demonstrate that RGS14 is a key regulator of signaling pathways linking synaptic plasticity in CA2 pyramidal neurons to hippocampal-based learning and memory but distinct from the canonical DG–CA3–CA1 circuit.
long-term potentiation hippocampus G protein signaling RGS proteins ERK
Footnotes
1To whom correspondence should be addressed. E-mail:jhepler@pharm.emory.edu.
Author contributions: S.E.L., J.P.S., Y.F., Y.S., J.D.S., D.W., K.J.R., S.M.D., and J.R.H. designed research; S.E.L., S.B.S., S.A.H., M.Z., C.P.V., D.P.C., S.R., and C.K.Y. performed research; S.E.L., S.B.S., M.Z., S.A.H., and J.P.S. analyzed data; and S.E.L., S.M.D., and J.R.H. wrote the paper.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at
+++++
PDF gratuito deste artigo aqui.
+++++
