EMERGING PATTERNS OF ASTROGLIA-NEURON INTERACTIONS IN NETWORK HYPEREXCITABILITY AND SEIZURES

Astroglial cells play pivotal roles in many brain processes, ranging from metabolic homeostasis to regulating key aspects of brain development, nurturing connectivity and computations. Accumulating evidence indicates that abnormal astroglial functioning contributes to the pathophysiology of many brain diseases, including diverse forms of epilepsy.
Previously we demonstrated distinct calcium dynamics in neurons and astroglia transitioning from pre-ictal to ictal activity and upon photic stimulation in hyperexcitable networks. In pre-ictal periods neurons were locally synchronised, whereas astroglia were highly active with global synchrony. Generalized seizures, however, were marked by a drastic, brain wide increase of astroglial and neuronal activity and synchrony. Knocking out astroglial glutamate transporters led to recurrent spontaneous seizures, accompanied by massive astroglial glutamate release, overall resembling a neonatal form of epileptic encephalopathy.
In the current work, we use combinations of genetic and pharmacological approaches to perturb astroglial calcium- and glutamate signalling, and glia-neuron interactions to further investigate their role in generation and spread of epileptic seizures. We utilize functional dual channel recording in zebrafish expressing neuronal and astroglial calcium indicators, as well as glutamate sensors in seizure prone animals and controls. Our results demonstrate multiple emerging interaction patterns between neural and astroglial populations as brain excitability increases. Furthermore, our perturbations of astroglial glutamate transporters alter these dynamics and the animals’ seizure susceptibility, suggesting astroglia as potential targets in the development of novel therapeutical approaches as well as an important regulators of excitability.