People with chronic epilepsy often suffer from memory problems. Researchers at the University of Bonn have just found a mechanism in mice that could explain these deficits. The German Center for Neurodegenerative Diseases (DZNE) also participated in the study. The results are published in the journal Brain, but a preliminary version is already available online.
Suppose you are going to visit an acquaintance whom you have not seen for a long time. Nevertheless, you ring the right doorbell without hesitation: the apple tree in the front yard with the wooden birdhouse next to it, the bright red painted fence, the clinker facade – all this indicates that you have come to the right place.
Each place has many characteristics that set it apart and make it unique as a whole. In order to remember a place, we must therefore store the combination of these characteristics (this can also include sounds or smells). Because only then can we recognize it with confidence when we visit it again and distinguish it from similar places.
It is possible that this retention of the exact combination of features is impaired in people with chronic epilepsy. At least the findings of the current study point in that direction.
“In the study, we looked at neurons in the hippocampus of mice,” says neuroscientist Dr. Nicola Masala from the Institute for Experimental Epileptology and Cognitive Science at University Hospital Bonn.
Specific neurons fire when a location is visited
The hippocampus is a region of the brain that plays a central role in memory processes. This is especially true for spatial memory: “In the hippocampus, there are so-called place cells,” says Masala. “These help us remember the places we have visited. There are about a million different place cells in the mouse hippocampus. And each responds to a combination of specific environmental characteristics. So, to put it simply, there is also a place cell for “apple tree/birdhouse/fence”.
But how to ensure that the place cell only responds to a combination of these three characteristics? This is ensured by a mechanism called “dendritic integration”. Because place cells have long extensions, dendrites. These are dotted with many contact points where the information transmitted to us by the senses about a place is captured (in fact, there are often hundreds or thousands of them). These contacts are called synapses. When signals arrive at several nearby synapses at the same time, a strong voltage pulse can form in the dendrite – a so-called dendritic spike.
In this way, the dendrite integrates different types of location information. Only when they are all together can it generate a spike. And only then is this combination recorded, so that we recognize the house of our acquaintance the next time we visit it.
“In mice with epilepsy, however, this process is impaired,” says Professor Heinz Beck, in whose research group Dr. Masala did his PhD and who is also a lecturer in the transdisciplinary research area “Life and Health ” at University. from Bonn. “In them, spikes already occur when only a few synapses are stimulated. Stimulation also doesn’t have to happen at exactly the same time. You could say: The place where the cells of sick rodents don’t look so closely. They shoot every house with an apple tree in the front yard. Therefore, the stored information is less specific. “We were able to show in our experiments that affected animals had much greater problems distinguishing familiar places from unfamiliar places,” Masala points out.
Active substances improve memory
But what is the reason? For a peak to form, large amounts of electrically charged particles (ions) must flow through the cell. For this purpose, pores open in the membrane that surrounds the dendrite – the ion channels. “In our laboratory animals, a special channel for sodium ions was significantly more prevalent than normal in the dendritic membrane,” says Dr. Tony Kelly of the Institute for Experimental Epileptology and Cognitive Sciences, who co-supervised the study. “This means that a few mistimed stimuli at the synapses are enough to open many channels and cause a spike. »
There are inhibitors that very specifically block the affected channel, preventing the influx of sodium ions. “We administered such a substance to the animals,” says Masala. “It normalized the firing behavior of their dendrites. They were also better able to remember the places they had visited. »
The study thus provides insight into the processes involved in memory retrieval. In addition, it gives hope in the medium term for the production of new drugs that can be used to improve the memory of epileptic patients. These promising results are also the fruit of a fruitful cooperation, underlines Masala: “Without the collaboration in particular with the laboratories of Prof. Dr. Sandra Blaess, from Prof. Dr. Laura Ewell and Prof. Dr. Christian Henneberger from the University of Bonn, this success would not have been possible. »
Participating Institutions and Funding:
In addition to University Hospital Bonn and the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), University College London and University of California Irvine participated in the study. The study was funded by the German Research Foundation (DFG).