Epilepsy
How NKCC1-mediated chloride dysregulation produces the hyperexcitability behind chronic seizures — and how bumetanide might help treat it.
Read moreNeurophysiology Lab · Universidad de Santiago de Chile
We study how neural circuits go awry, using electrophysiological recordings in animal models to investigate the mechanisms underlying epilepsy and autism spectrum disorder. Although these conditions differ widely in their clinical presentation, our work traces a common thread through both: the disruption of chloride cotransport and GABAergic inhibition in hippocampal circuits.
The chloride cotransporters NKCC1 and KCC2 set the intracellular chloride balance that determines whether GABA acts as an inhibitory signal in the brain. In our pilocarpine model of epilepsy, elevated NKCC1 activity shifts this balance in the hippocampus, weakening inhibition so that circuits become prone to seizures. In our valproic acid (VPA) model of the autism spectrum, we study the same chloride machinery in dentate gyrus granule cells, where altered excitability may help explain the well-known overlap between autism and epilepsy. This shared mechanism is also the basis of our translational work, which seeks to repurpose bumetanide, an NKCC1 inhibitor, as a therapeutic candidate.
Research lines
We approach epilepsy and the autism spectrum not as unrelated conditions, but as different behavioral outcomes of a shared vulnerability in inhibitory signaling.
Approach
We combine in vitro hippocampal electrophysiology with behavioral phenotyping in genetic and pharmacological animal models — work that has also driven translational studies repurposing chloride cotransporter inhibitors as therapeutic candidates.
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