Investigating the Permissive Environment of Perisynaptic Astroglia for Information Storage in the Dentate Gyrus

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Nam, A.J.
Kuwajima, M.
Mendenhall, J.M.
Hubbard, D.D.
Hanka, D.C.
Parker, P.H.
Wetzel, A.
Bartol, T.M.
Sejnowski, T.J.
Abraham, W.C.

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Perisynaptic astroglial processes (PAPs), are active modulators of neuronal activity and directly contribute to information processing in the brain. Both in vivo and in vitro experiments have demonstrated that PAPs undergo activity-dependent structural changes. Thus, here we employ cutting-edge resources at the Texas Advanced Computing Center (TACC) to explore PAP structural remodeling associated with long-term potentiation (LTP) and long-term depression (LTD) that may help support local changes in information processing. Long-term potentiation (LTP) and long-term depression (LTD), widely accepted cellular mechanisms of learning and memory, were induced in vivo in the awake adult rat hippocampal dentate gyrus. LTP induction in the middle molecular layer (MML) was achieved by delta-burst stimulation in the medial perforant pathway, a procedure that produced concurrent long-term depression (cLTD) in the outer molecular layer (OML). The contralateral control hemisphere received only baseline stimulation to the medial perforant path. Three-dimensional electron microscopy (3DEM) offers significant advantages over two-dimensional approaches including a more complete view of ultrastructure in all X-Y-Z planes. AlignEM Swift, the state-of-the-art interactive application available at TACC, is integral for achieving the standard of perfect serial section image alignment needed for 3DEM analysis. Furthermore, Blender at TACC, equipped with the computing power of TACC’s supercomputers, similarly facilitates large-scale and realistic PAP reconstructions for visualization and quantitative mesh analysis. Changes to PAP ultrastructure have important implications on the spatiotemporal dynamics of astrocyte calcium signaling. Thus, TACC resources will further enable computational modeling to investigate the functional consequences of PAP morphological changes. Preliminary analysis suggests that more than 80% of all dentate gyrus synapses exhibit some degree of PAP apposition at the axon-spine interface (ASI). Results from this study made possible using TACC systems will contribute to our overall understanding of the cellular mechanism of information processing and the role of specifically astrocytes in this process.


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