Researchers discover new data on memory impairment in epilepsy

Imagine that you choose to catch up with a buddy you haven’t seen in a long. But as soon as you spot the apple tree in the front yard with the wooden birdhouse next to it, the brightly painted red fence, and the clinker facade, you automatically ring the appropriate doorbell. Every place has a range of distinguishing features that set it different and help people identify it as a whole. In order to remember a place, we must consequently preserve a record of the mix of these attributes (this can also include sounds or smells).

We won’t be able to differentiate it from other places or recognise it with certainty when we return until then. It’s conceivable that persons with persistent epilepsy have trouble remembering the precise mix of traits. The results of the present investigation, at least, indicate in this way.

“In the study, we looked at neurons in the hippocampus of mice,” explains neuroscientist Dr Nicola Masala of the Institute of Experimental Epileptology and Cognitive Sciences at the University Hospital Bonn. Specific neurons fire when a place is visited. The hippocampus is a region in 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,” Masala says.

“These help us remember places we have visited.” There are about one million different place cells in the mouse hippocampus. And each response to a combination of specific environmental characteristics. So, to put it simply, there is also a place cell for “apple tree/birdhouse/fence”.

The place cell only reacts to a combination of these three properties, but how is that made sure? This is made possible by a process called “dendritic integration.” The dendrites of place cells are lengthy extensions. These are peppered with multiple points of touch where we get up information about a location from our senses (de facto, there are often hundreds or thousands of them).

“In mice with epilepsy, however, this process is impaired,” explains Prof. Dr Heinz Beck, in whose research group Dr Masala did her doctorate and who is also a speaker of the Transdisciplinary Research Area “Life and Health” at the University of Bonn.

“In them, the spikes already occur when only a few synapses are stimulated. Nor does the stimulation have to occur at exactly the same time.” One might say: The place cells of sick rodents do not look so carefully. They fire at all the houses with an apple tree in the front yard. As a result, the information stored is less specific. “We were able to show in our experiments that the affected animals had significantly greater problems distinguishing familiar places from unfamiliar ones,” Masala points out.

They are referred to as synapses. A powerful voltage pulse, or so-called dendritic spike, may emerge in the dendrite when impulses reach numerous nearby synapses at once.
The dendrite combines many sorts of location data in this manner. The only time a spike may occur is when they all come together. Only then is this combination saved, enabling us to recognise the friend’s home the following time we go there.

Memory is enhanced by active chemicals.

But why is this happening? Large numbers of electrically charged particles (the ions) must enter the cell for a spike to occur. The membrane that encloses the dendrite, which contains the ion channels, opens holes for this reason.” In our lab animals, a special channel for sodium ions was significantly more prevalent than normal in the dendrite membrane,” Dr Tony Kelly of the Institute of Experimental Epileptology and Cognitive Sciences, who co-supervised the study, explains. “This means that just a few poorly synchronized stimuli at the synapses are enough to open many channels and elicit a spike.”

Inhibitors exist that very precisely block the impacted channel, stopping the flow of sodium ions. “We administered such a substance to the animals,” Masala says. “This normalized the firing behaviour of their dendrites. They were also better able to remember places they had visited.”

The study thus provides insight into the processes involved in memory retrieval. In addition, in the medium term, it gives rise to hopes of producing new drugs that can be used to improve the memory of epilepsy patients. These promising results are also the result of fruitful cooperation, Masala emphasizes: “Without the collaboration especially with the laboratories of Prof. Dr Sandra Blaess, Prof. Dr Laura Ewell and Prof. Dr Christian Henneberger at the University of Bonn, this success would not have been possible.”