Dr. Glykys is a child neurologist and his main research interests are:
- how the brain inhibition system works at the cellular level, and
- how the dysfunction in the inhibition system can lead to seizures with special emphasis in post-traumatic seizures and neonatal seizures.
One of our main problems with pediatric seizures is the significant failure rate of our current medical treatments due to an incomplete understanding of how the inhibitory system works in the brain.
The neurotransmitter GABA mediates inhibition in the mature brain. However, GABA can actually excite a neuron during early development and after brain insults. The net action of GABA depends on the relation between the chloride (Cl-) concentration inside and outside the neuron. In mature neurons, Cl- is low inside the neurons. In early development and pathological conditions, Cl- is high in neurons. When GABA binds to its receptor, it opens a channel that allows the flow of Cl- until it reaches a point where no more can move (its equilibrium potential [ECl]). Thus, if a neuron has low Cl-, GABA will allow Cl- to enter the neuron and inhibit it. When Cl- is high, GABA will allow Cl- to exit the neuron and depolarize it.
One therapeutic approach to enhance inhibition in the brain is to decrease the neuronal Cl- concentration and improve the efficacy of anticonvulsive medications that activate GABAA receptors. We use electrophysiology and 2-photon imaging of a Cl- sensitive genetically encoded fluorophore to address our scientific questions.
Our results will not only provide new treatments for pediatric seizures but will also be applicable to other brain injuries that lead to Cl- increase like traumatic brain injury. We will also better understand how the brain’s inhibitory network works.