Plasticity in cortical networks & epilepsy
Our lab explores the
pathophysiology of focal epilepsies with a specific focus on the function and plasticit of cortical synapses and networks. Our recent work has focused on alterations of neuronal chloride homeostasis in focal epilepsies and the functional impact of mutations associated with epileptic encephalopathies.
Our aim is to resolve the cellular architecture of epileptic networks an identfy key cellular determinants that could represent novel therapeutic
targets for pharmaco-resistant epilepsies.
Currently,
our main projects
focus on:
The
neuronal mechanisms of chloride ion transport: since GABAA
receptors are
mainly permeable to chloride ions, the currents they carry are directly
influenced by transmembrane gradients of chloride in neurons. We study
the
function and regulation of the chloride/cation co-transporter KCC2,
which
exerts a major control over these gradients in mature cortical neurons (Chamma
et al J Neurosci 2013 ; Heubl et al Nat Comm 2017 ; Otsu et al J Physiol 2020 ; Al Awabdh et al 2022) as well
the functional impact of its down-regulation, as observed in most forms of focal epilepsies as well as other neurological and psychiatric disorders (Gauvain et al
PNAS 2011 ; Chevy et al J
Neurosci 2015 ; Goutierre et al Cell Rep 2019; Simonnet et al Neuropsychopharmacology 2023). Recent work investigated the therapeutic potential of targeting KCC2 in mesial temporal lobe epilepsy, the most frequenf form of focal epilepsy in adults (Donneger et al biorXiv 2023). Ongoing work also explores the functional impact of mutations in the Slc12a5 gene, encoding KCC2, on cortical development and function.
Experimental
approaches
We use a multidisciplinary approach combining:
• in vitro (patch
clamp, LFP and MEA) and in vivo (telemetric ECoG, intracerebral silicon probes)
electrophysiology
• anterograde tracing and genetic
expression/suppression
using viral vectors
• optogenetics
• optical imaging on live neurons
• super-resolution microscopy (STED/PALM/STORM)
• single molecule tracking using quantum dots
• biochemistry and proteomics