The Calm Between the Storms
Electrical activity is omnipresent in our brain as the cells communicate. An epileptic seizure occurs when there is a sudden synchronous burst of intense electrical activity in the brain. To control the excitability of neurons, small transporters, among them excitatory amino acid transporter 2 (EAAT2), play a key role by removing of extracellular glutamate, which is the main excitatory neurotransmitter in the brain. Impaired glutamate clearance by EAAT2 has been shown to lead to accumulation of glutamate, resulting in an overactive brain. This in turn may cause epilepsy and makes it essential to understand how a loss of EAAT2 affects brain cells. Stephan Neuhauss from the Department of Molecular Life Sciences at the University of Zurich and colleagues used zebrafish to generate a deeper understanding of this process.
Zebrafish have a relatively simple nervous system and the optical transparency of the embryos permits real-time imaging of neural activity. Stephan Neuhauss and colleagues generated zebrafish strains that lack of EAAT2 and transgenically labelled neurons with an activity indicator. In that case, cells that are excited light up. The researchers indeed saw impressive synchronized activity of brain cells, confirming that the zebrafish exhibit spontaneous epileptic seizures. These seizures were also correlated with a rapid increase in extracellular glutamate. In further experiments, they showed that these spontaneous seizures can also be evoked by sensory input, e.g. by light or acoustic stimulation. Counterintuitively, the researchers observed that although the brain was over excitable, in the periods between epileptic events, the neural and swimming activity of the brain was lower than in unaffected zebrafish.
These findings point towards strategies of the brain to keep a balanced overall brain activity that the researchers would like to understand better and use in the future to control epilepsy in patients.
By: Stephan Neuhauss, Department of Molecular Life Sciences, University of Zurich
Reference: Hotz A.L., Jamali, A., Rieser, N.N., Niklaus, S., Aydin, E., Myren-Svelstad, S., Lalla, L., Jurisch-Yaksi, N., Yaksi, E., Neuhauss, S.C.F. (2022). Loss of glutamate transporter eaat2a leads to aberrant neuronal excitability, recurrent epileptic seizures, and basal hypoactivity. Glia (2021).