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:
Maryalice Yakutchik | Newswise Science News
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy