Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Johns Hopkins scientists create forgetful mouse

10.03.2003


Studying mice, scientists from Johns Hopkins have successfully prevented a molecular event in brain cells that they’ve found is required for storing spatial memories. Unlike regular mice, the engineered rodents quickly forgot where to find a resting place in a pool of water, the researchers report in the March 7 issue of the journal Cell.



The experiments are believed to be the first to prove that subtly altering the chemistry of a certain protein can profoundly affect a brain cell’s ability to respond to external stimulation, a process called neuronal plasticity, long thought to underlie learning and memory.

By genetically altering part of a receptor that binds glutamate -- the most important excitatory chemical in the brain -- the scientists created a version of the protein that could not be modified by adding phosphate groups. In their experiments, preventing phosphorylation of the receptor kept it from responding normally to external stimulation in the lab and limited how long animals could store new memories.


"Since 1986, phosphorylation has been recognized as a key to modulating receptor responses to neurotransmitters like glutamate, but this is the first demonstration that phosphorylation of a particular target protein mediates the processes we believe are behind learning and memory," says Richard Huganir, Ph.D., professor of neuroscience in the Johns Hopkins School of Medicine’s Institute for Basic Biomedical Sciences. "This new work shows that phosphorylation of this target protein does indeed affect an animal’s ability to remember."

Mice with the "phosphate-free" version of the protein, known as GluR1, learned to find a hidden platform in a pool of water as well as normal mice, but couldn’t remember its position eight hours later, the researchers report. In contrast, normal mice remembered what they’d learned even after 24 hours.

"Rodents’ spatial learning and memory is highly developed because they must navigate a complex environment in their natural habitat and doing so correctly is crucial to their survival and safety," says Michela Gallagher, Ph.D., professor of psychological and brain sciences in the Krieger School of Arts and Sciences at The Johns Hopkins University. "The neuronal processes behind this form of learning are a convenient and measurable test of learning and memory."

The neuronal plasticity involved in spatial learning may also play a large role in the "wiring" of the brain during development, and in conditions such as epilepsy, addiction, chronic pain and others in which repeated experience creates new memories, the researchers say.

Huganir studies the role of receptor phosphorylation in two neuronal processes, long-term depression (LTD) and long-term potentiation (LTP), that affect a neuron’s ability to communicate with neighboring neurons at points called synapses. By improving communication with a specific neuron and inhibiting communication with others, new neuronal pathways are formed, and each pathway is thought to represent a particular memory, says Huganir.

Communication, or transmission, at a given synapse depends on how the local receptors change in response to stimulation, either artificial (applying an electrical stimulation) or natural (i.e., looking for the platform in a pool).

To increase communication between two neurons, as in LTP, new receptors can be shipped to the front line or the function of existing receptors can be enhanced. To inhibit communication, as in LTD, receptors at the synapse may be recalled or their function diminished. These processes are due -- at least in part -- to phosphorylation of proteins that make up the various receptors, Huganir thinks.

Their experiments with neurons from the hippocampus of mice engineered to make only the "phosphate-free" version of GluR1 prove that phosphorylation of the protein is crucial for LTD and LTP to take place.

"We’ve established that the two phosphorylation sites on GluR1 are crucial for retention of spatial learning, but it is likely that other sites in other subunits of this glutamate receptor will also play a role," says Huganir.

Glutamate not only elicits many normal neuronal responses but excessive amounts can actually cause neurons to die. So-called glutamate toxicity is thought to contribute to certain neurological diseases, including epilepsy, stroke and amyotrophic lateral sclerosis, or ALS. Understanding how glutamate receptors are regulated could one day affect treatment of these disorders, say the researchers.

The experiments were funded by the Howard Hughes Medical Institute, the Robert Packard Center for ALS Research at Johns Hopkins, and the National Institutes of Health.

Authors on the report are Huganir, Hey-Kyoung Lee, Kogo Takamiya, Hengye Man, Chong-Hyun Kim, Gavin Rumbaugh, Sandy Yu, Lin Ding and Chun He of the Johns Hopkins School of Medicine; Gallagher and Jung-Soo Han of The Johns Hopkins University; and Ronald Petralia and Robert Wenthold of the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/
http://www.cell.com/

More articles from Life Sciences:

nachricht Biomarkers for identifying Tumor Aggressiveness
26.07.2017 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

nachricht The dense vessel network regulates formation of thrombocytes in the bone marrow
25.07.2017 | Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA mission surfs through waves in space to understand space weather

25.07.2017 | Physics and Astronomy

Strength of tectonic plates may explain shape of the Tibetan Plateau, study finds

25.07.2017 | Earth Sciences

The dense vessel network regulates formation of thrombocytes in the bone marrow

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>