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 Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>