Faulty Connection: Disturbed transmission of signals in the cerebrum promises new findings for epilepsy research
Click to enlarge. Caption see below.
Using precise tracing techniques and genetically modified mice, the researchers visualized fiber bundles and synaptic contacts between the temporal lobe and the hippocampus. In the healthy brain, a signaling path involved in language understanding and visual recognition leads from the edge of the temporal lobe to the hippocampus, a zone of the cerebrum that is important particularly for the formation of memory content. From an anatomical perspective, the entry channel to the hippocampus runs along a system of fibers in which electrical signals are transmitted to particular cell groups. The stimuli are sorted in the first cell group, passed on to the second, and then sent back to the temporal lobe. Stated in simplified terms, this is how information on the environment is prepared and stored for further processing.
But what happens to this circuit under epileptic conditions? Haas and her colleagues demonstrated that the signal from the hippocampus back to the temporal lobe – the last step – fails shortly after an epileptic reaction starts, whereas it remains intact on the path leading to the hippocampus. The researchers were surprised to discover that new synaptic contacts develop within this circuit and that the size and complexity of the synapses increase. These structural changes could lead to an increase in the transmission of signals and ultimately to an increased risk for seizures. In vitro studies confirmed the suspicion that one of the involved cell types is excited more strongly than normal in epileptic mice. The researchers assume that these cells might function as highly interconnected epileptic nodes in the hippocampus and that the excitatory circuit might cause pathological changes there in particular. “The issue is of special significance, because it is not yet entirely clear which factors in the hippocampus contribute to triggering epileptic seizures,” says Haas.
The team now plans to investigate the entire modified chain of signals between the temporal lobe and the hippocampus. In particular, they aim to study whether the boost in the entry signal is a cause or an effect of epileptic activity. The researchers are also interested in determining which molecular mechanisms form the basis of synaptic modifications. Further studies will presumably result in the discovery of new therapeutic or preventive strategies. For example, Haas sees therapeutic potential in the modification of the affected areas: “If we could reduce the excitation of the hippocampus, for instance by means of cell-specific genetic manipulation, it might be possible to decrease the severity of epilepsy and at the same time lower the side-effects of therapy. However, we need to conduct further research to achieve this ambitious goal.”
Figure Legend
Three-dimensional representation of the granule cells in the hippocampus (green) and the fibers leading to the cerebral cortex (magenta), highlighted by fluorescent dyes. Copyright: Cerebral Cortex, Oxford University Press
Original publication:
Janz P, Savanthrapadian S, Häussler U, Kilias A, Nestel S, Kretz O, Kirsch M, Bartos M, Egert U, Haas CA (2016) Synaptic remodeling of entorhinal input contributes to an aberrant hippocampal network in temporal lobe epilepsy. Cerebral Cortex.
DOI: 10.1093/cercor/bhw093
URL: http://cercor.oxfordjournals.org/content/early/2016/04/12/cercor.bhw093.short?rss=1
Contact:
Prof. Dr. Carola Haas
Experimental Epilepsy Research
Department of Neurosurgery, Medical Center – University of Freiburg
Phone: +49 (0)761/270-52950
E-Mail: carola.haas@uniklinik-freiburg.de
Levin Sottru
Science Communicator
Cluster of Excellence BrainLinks–BrainTools
University of Freiburg
Phone: +49 (0)761/203-67721
E-Mail: sottru@blbt.uni-freiburg.de
Michael Veit
Science Communicator
Bernstein Center Freiburg
University of Freiburg
Phone: +49 (0)761/203-9322
E-Mail: michael.veit@bcf.uni-freiburg.de
Printable version (pdf) of the press release.
German Press Release