Cortical microcircuitry after traumatic brain injury: molecules to networks
Neuronal disconnection and long-term circuit rewiring are the driving events responsible for acute clinical deficits and recovery, respectively, after traumatic brain injury. Therefore, a translation-oriented understanding of TBI must occur at the level of neuronal microcircuitry and networks. Yet few details are available on how structural connectivity of diverse neuronal subpopulations is affected by TBI. Furthermore, the regulatory cascades, both intracellularly and extracellularly, are not well understood with sufficient specificity for therapeutic purposes to prevent connectivity loss or to enhance recovery. In this collaborative project, we will use closed TBI model to study 1) how principal and inhibitory interneuron microcircuit connectivity in the cortex respond to TBI over time, 2) intracellular signaling events that modulate connectivity loss and eventually prime functional recovery and 3) changes within the extracellular matrix and their contribution to neuronal connectivity. We propose to use multi-disciplinary approaches of intersectional mouse genetics, viral tracing and manipulation of population specific circuit and/or single cell activity, quantitative proteomics, and high-resolution imaging together with detailed kinematic analyses. We aim that our collective effort to understand changes at the level of identified molecules contribute to neurocircuit functions and ultimately facilitate discovery of potential drug targets for TBI patients.
Molecular modelling techniques, Imaging techniques, Pharmacology, Behavioural methodologies, "omics" approaches, Neurocircuits, viral tracing and manipulation, extracellular matrix, intracellular signaling
2017 - 2021
Aya Takeoka (Coordinator)
United Kingdom (MRC)