TIRF imaging of primary cortical astrocyte transfected with fluorescently tagged vGLUT3 to visualize vesicle movement.

     One major focus of our lab is studying how mutant huntingtin expressing astrocytes contribute to HD. The astrocyte plays a critical role in nervous system function and development. Astrocytes are important for homeostasis, including providing the neuron with energy and substrates for neurotransmission. In HD brains morphological changes in astrocytes are seen as disease progresses. There are also gene expression changes in the glial specific glutamate transporter GLT-1 in HD patient tissue, that could lead to decreased uptake of the excitatory neurotransmitter glutamate. These changes have been recapitulated in some mouse models of HD. We found in primary astrocytes from the BACHD mouse model, increase levels of extracellular glutamate released after stimulating Ca2+ dependent vesicular release of glutamate. We are studying the mechanisms at play that could lead to increased levels of glutamate within and release from astrocytes. We are exploring the mechanisms that contribute to this change using molecular, cellular and imaging techniques.