New findings on the link between nerve cells at the interface to the hippocampus
Neuroscientists in Bonn and Heidelberg have succeeded in providing new insights into how the brain works. Researchers at the DZNE and the German Cancer Research Center (DKFZ) analyzed tissue samples from mice to identify how two specific proteins, ‘CKAMP44’ and ‘TARP Gamma-8’, act upon the brain’s memory center.
These molecules, which have similar counterparts in humans, affect the connections between nerve cells and influence the transmission of nerve signals into the hippocampus, an area of the brain that plays a significant role in learning processes and the creation of memories.
The results of the study have been published in the journal Neuron.Brain function depends on the active communication between nerve cells, known as neurons. For this purpose, neurons are woven together into a dense network where they constantly relay signals to one another. However, neurons do not form direct contacts with each other. Instead they are separated by an extremely narrow gap, known as the synapse. This gap is bridged by ‘neurotransmitters’, which carry nerve signals from one cell to the next.
Specific molecular complexes in the cell’s outer shell, so-called ‘receptors’, receive the signal by binding the neurotransmitters. This triggers an electrical impulse in the receptor-bearing cell and thus the nerve signal has moved on one neuron further.
In the current study, a team led by Dr Jakob von Engelhardt focused on the AMPA receptors. These bind the neurotransmitter glutamate and are particularly common in the brain. “We looked at AMPA receptors in an area of the brain, which constitutes the main entrance to the hippocampus,” explains von Engelhardt, who works for the DZNE and DKFZ. “The hippocampus is responsible for learning and memory formation. Among other things it processes and combines sensory perception. We therefore asked ourselves how the flow of information into the hippocampus is controlled.”
A pair of helpers
Dr von Engelhardt’s research team specifically focused on two protein molecules: ‘CKAMP44’ and ‘TARP Gamma-8’. These proteins are present, along with AMPA receptors, in the ‘granule’ cells, which are neurons that receive signals from areas outside of the hippocampus. It was already known that these proteins form protein complexes with AMPA receptors. “We have now found out that they exert a significant influence on the functioning of glutamate receptors. Each in its own way, as chemically they are completely different,” says the neuroscientist. “We identified that the ability of a nerve cell to receive signals doesn’t depend solely on the actual receptors; CKAMP44 and TARP Gamma-8 are just as important. Their function cannot be separated from that of the receptors.”
This was the result of an analysis in which the researchers compared brain tissue from mice with a natural genotype with brain tissue from genetically modified mice. Neurons in the genetically modified animals were not able to produce either CKAMP44 or TARP Gamma-8 or both.
The researchers discovered, among other things, that both proteins promote the transportation of glutamate receptors to the cell surface. “This means they influence how receptive the nerve cell is to incoming signals,” says von Engelhardt.
However, the number of receptors and thus the signal reception can be altered by neuronal activity. The von Engelhardt group found that in this regard the auxiliary molecules have different effects: TARP Gamma-8 is essential to ensure that more AMPA receptors are integrated into the synapse following a plasticity induction protocol, whereas CKAMP44 plays no role in this context. “Synapses alter their communication depending on their activity. This ability is called plasticity. Some of the changes involved are only temporary, others may last longer,” explains von Engelhardt. “TARP Gamma-8 influences long-term plasticity. It makes the cell able to strengthen synaptic communication for a prolonged time-period. The larger the number of receptors on the receiving side of the synapse, the better the neuronal connection.”
The number of receptors doesn’t change suddenly, but remains largely stable for a certain amount of time. “This condition may last for hours, days or even longer. This long-term effect is essential for the creation of memories. We can only remember things if the connections between neurons undergo a long-lasting change,” says the scientist.
Fast sequence of signals
However, CKAMP44 and TARP Gamma-8 also act over shorter periods of time. The research team discovered that the molecules affect how quickly the AMPA receptors return to a receptive state. “If glutamate has docked on to a receptor, it takes a while until the receptor can react to the next neurotransmitter. CKAMP44 lengthens this period. In contrast, TARP Gamma-8 helps the receptor to recover more quickly,” says von Engelhardt.
Hence, CKAMP44 temporarily weakens the synaptic connection, while TARP Gamma-8 strengthens it. Through the interplay of these proteins the synapse is able to tune its sensitivity to a specific level. This condition can last from milliseconds to a few seconds before the strength of the connection is again adapted. Specialists refer to this as “short-term plasticity”.
“These molecules ultimately influence how well the nerve cell is able to react to a rapid succession of signals,” the scientist summarises the findings. “Such a rapid firing enables neuronal networks to synchronize their activity, which is a common process in the brain.”
Much to the researchers’ surprise, it turned out that the two proteins influence not only the synapse but also the shape of the nerve cells. In the absence of these auxiliary molecules, the neurons have fewer dendrites to establish contact with other nerve cells. “The organism can use CKAMP44 and TARP Gamma-8 molecules to regulate neuronal connections in a number of ways,” von Engelhardt says. “This ability depends on the balance between the partners, as to some extent they have a contrary effect. The way in which the neurons of the hippocampus react to signals from other regions of the brain is therefore highly dependent on the presence and the expression ratio of these molecules.”
Since the two molecules act directly on the structure and function of synapses of granule cells, Jakob von Engelhardt considers it probable that they also have an influence on learning and memory.
Co-expressed auxiliary subunits exhibit distinct modulatory profiles on AMPA receptor function.
Konstantin Khodosevich, Eric Jacobi, Paul Farrow, Anton Schulmann, Alexandru Rusu, Ling Zhang, Rolf Sprengel, Hannah Monyer, Jakob von Engelhardt. Neuron (2014). doi:10.1016/j.neuron.2014.07.004.
A video abstract is availbale at
Dr. Marcus Neitzert
+49 (0) 228/43302-271
Dr. Stefanie Seltmann
Head of Press and Public Relations
+49 (0) 6221/422854
Dr. Marcus Neitzert | idw - Informationsdienst Wissenschaft
How Invasive Plants Influence an Ecosystem
28.07.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Perseus translates proteomics data
27.07.2016 | Max-Planck-Institut für Biochemie
Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.
To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...
A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology
On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...
Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.
While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.
Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.
Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...
Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases
Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...
15.07.2016 | Event News
15.07.2016 | Event News
11.07.2016 | Event News
29.07.2016 | Health and Medicine
29.07.2016 | Physics and Astronomy
28.07.2016 | Information Technology