Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Reveal Molecular Sculptor of Memories

27.09.2011
Researchers working with adult mice have discovered that learning and memory were profoundly affected when they altered the amounts of a certain protein in specific parts of the mammals’ brains.

The protein, called kibra, was linked in previous studies in humans to memory and protection against late-onset Alzheimer’s disease. The new work in mice, reported in the Sept. 22 issue of Neuron, shows that kibra is an essential part of a complex of proteins that control the sculpting of brain circuitry, a process that encodes memory.

“There are populations of humans who are slightly smarter and have better memory recall than others, and these traits have been mapped to the gene that codes for the kibra protein” says Richard L. Huganir, Ph.D., professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine, and a Howard Hughes Medical Institute investigator. “Our studies in mice show that this same gene is involved in the operation of synapses, through which neurons communicate, and in brain plasticity, suggesting that’s what its role might be in humans too.”

In their lab, Huganir and neuroscience graduate student Lauren Makuch isolated kibra from mouse brain cells and confirmed by standard biochemical tests that it interacted with a neurotransmitter receptor in the brain known as the AMPA receptor.

They then determined that kibra regulated the delivery of AMPA receptors from inside the brain’s nerve cells out to the synapses by first growing live brain cells from embryonic mice in a dish for two weeks and then genetically altering some of those cells to produce less kibra protein. Next, they placed the live neurons in an imaging chamber and recorded the activity of the AMPA receptors once a minute for 60 minutes. Results showed that AMPA receptors moved faster in the cells with less kibra than in control cells with normal amounts of the protein demonstrating that kibra regulates how receptors are delivered to the surface of brain cells.

The work affirms that the addition of AMPA receptors to synapses serves to strengthen connections in the brain, Huganir says, noting that most forms of learning involve the strengthening of some synapses and the weakening of others, a phenomenon known as plasticity, which is responsible for sculpting circuits in the brain that encode memory. Without kibra, this process doesn’t function properly; as a result, learning and memory are compromised. Huganir hypothesizes that kibra specifically helps create a pool of receptors that is used to add receptors to synapses during learning.

Later in their study, using slices of brain from mice with or without kibra, postdoctoral fellow Lenora Volk recorded and measured electrical activity and synaptic plasticity in nerve cells, noting that mice lacking kibra showed less plasticity, a phenomenon that translates into a reduced ability to learn and recall new information, Makuch explains.

Finally, the Hopkins researchers conducted a series of behavioral studies using adult mice to compare the learning and memory of normal mice with those that made much less kibra protein. They used a well-established fear-conditioning task by placing the mice in a training chamber and exposing them to a tone and subsequent shock. After two days of training, the animals’ rates of “freezing” in place — a normal rodent response to fear — were measured. Kibra-deficient mice took longer to learn to associate the tone with the shock than it did the others. On day three of the experiment, upon simply being placed back into the training chamber, the normal mice had a high rate of freezing, while the kibra-deficient mice had a very low rate, indicating impairments in contextual fear response and therefore, memory.

“Our work in the mammalian brain shows that kibra, required for normal brain function and associated with learning and memory, is important for regulating the trafficking of AMPA receptors,” Huganir says. “In addition, as kibra has been associated with protection against early onset Alzheimer’s disease, these studies may help define novel therapeutic targets for the treatment of age-related memory disorders.”

This study was funded by the National Institutes of Health and the Howard Hughes Medical Institute.

Authors on the paper, in addition to Huganir, Makuch and Volk are Victor Anggono, Richard C. Johnson, and Yilin Yu, all of Johns Hopkins.

Other authors are Kerstin Duning and Joachim Kremerskothen, University Hospital Münster, Germany; Jun Xia, The Hong Kong University of Science and Technology, China; and Kogo Takamiya, University of Miyazaki, Japan.

On the Web:
Richard L. Huganir: http://neuroscience.jhu.edu/RichardHuganir.php
Neuron: http://www.cell.com/neuron/

Maryalice Yakutchik | Newswise Science News
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>