Meeting Report: NeuroFrance 2023 Florian Donneger Thesis Report
Meeting Reports
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May 24, 2023
Summary
During my thesis, I focused on the pathophysiology of temporal lobe epilepsies (TLE). Specifically, my research centered around the potassium/chloride cotransporter KCC2, whose dysregulation in various forms of epilepsy contributes to the emergence of pathological activities that lead to seizures. I contributed to three studies exploring the expression, function, and regulation of KCC2.
I revealed similar mechanisms of chloride ion homeostasis regulation in principal neurons and interneurons of the hippocampus. Additionally, I identified new protein partners of KCC2 and unexpectedly demonstrated that its interaction with gephyrin regulates its membrane expression and function.
The core of my thesis focused on exploring the therapeutic potential of two controversial KCC2 potentiators in TLE. Through a combination of in vitro electrophysiology, single-particle tracking, cell biology, and biochemistry techniques, I uncovered their efficacy and mechanism of action. Subsequently, I conducted recordings of postoperative human epileptic tissues and electrocorticography (ECoG) recordings in a murine model of TLE to demonstrate the therapeutic benefit of these compounds. These findings resulted in a patent application and a manuscript, of which I am the first author.
Summary
During my thesis, I focused on the pathophysiology of temporal lobe epilepsies (TLE). Specifically, my research centered around the potassium/chloride cotransporter KCC2, whose dysregulation in various forms of epilepsy contributes to the emergence of pathological activities that lead to seizures. I contributed to three studies exploring the expression, function, and regulation of KCC2.
I revealed similar mechanisms of chloride ion homeostasis regulation in principal neurons and interneurons of the hippocampus. Additionally, I identified new protein partners of KCC2 and unexpectedly demonstrated that its interaction with gephyrin regulates its membrane expression and function.
The core of my thesis focused on exploring the therapeutic potential of two controversial KCC2 potentiators in TLE. Through a combination of in vitro electrophysiology, single-particle tracking, cell biology, and biochemistry techniques, I uncovered their efficacy and mechanism of action. Subsequently, I conducted recordings of postoperative human epileptic tissues and electrocorticography (ECoG) recordings in a murine model of TLE to demonstrate the therapeutic benefit of these compounds. These findings resulted in a patent application and a manuscript, of which I am the first author.
