@article{ddd.uab.cat:250138,
      author = {Masvidal Codina, Eduard and Smith, Trevor M. and Rathore, Daman
               and Gao, Yunan and Illa, Xavi and Prats-Alfonso, Elisabet and Del
               Corro, Elena and Bonaccini Calia, Andrea and Rius, Gemma and
               Martin-Fernandez, Iñigo and Guger, Christoph) and Reitner,
               Patrick) and Villa, Rosa and Garrido, Jose and Guimerà Brunet,
               Anton and Wykes, Robert C},
       title = {Characterization of optogenetically-induced cortical spreading
               depression in awake mice using graphene micro-transistor arrays},
     journal = {Journal of Neural Engineering},
        year = {2021},
      volume = {18},
      number = {5},
       pages = {55002--},
       month = {10},
    abstract = {Objective. The development of experimental methodology utilizing
               graphene micro-transistor arrays to facilitate and advance
               translational research into cortical spreading depression (CSD)
               in the awake brain. Approach. CSDs were reliably induced in awake
               nontransgenic mice using optogenetic methods. High-fidelity DC-
               coupled electrophysiological mapping of propagating CSDs was
               obtained using flexible arrays of graphene soultion-gated field-
               effect transistors (gSGFETs). Main results. Viral vectors
               targetted channelrhopsin expression in neurons of the motor
               cortex resulting in a transduction volume 1 mm3. 5-10 s of
               continous blue light stimulation induced CSD that propagated
               across the cortex at a velocity of 3.0 0.1 mm min-1. Graphene
               micro-transistor arrays enabled high-density mapping of infraslow
               activity correlated with neuronal activity suppression across
               multiple frequency bands during both CSD initiation and
               propagation. Localized differences in the CSD waveform could be
               detected and categorized into distinct clusters demonstrating the
               spatial resolution advantages of DC-coupled recordings. We
               exploited the reliable and repeatable induction of CSDs using
               this preparation to perform proof-of-principle pharmacological
               interrogation studies using NMDA antagonists. MK801 (3 mg kg-1)
               suppressed CSD induction and propagation, an effect mirrored,
               albeit transiently, by ketamine (15 mg kg-1), thus demonstrating
               this models' applicability as a preclinical drug screening
               platform. Finally, we report that CSDs could be detected through
               the skull using graphene micro-transistors, highlighting
               additional advantages and future applications of this technology.
               Significance. CSD is thought to contribute to the pathophysiology
               of several neurological diseases. CSD research will benefit from
               technological advances that permit high density
               electrophysiological mapping of the CSD waveform and propagation
               across the cortex. We report an in vivo assay that permits
               minimally invasive optogenetic induction, combined with
               multichannel DC-coupled recordings enabled by gSGFETs in the
               awake brain. Adoption of this technological approach could
               facilitate and transform preclinical investigations of CSD in
               disease relevant models.},
         doi = {10.1088/1741-2552/abecf3},
         url = {https://ddd.uab.cat/record/250138},
}