Role of Perisynaptic Astroglia during Plasticity in a Synaptic Cluster

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Nam, Andrea J.
Kuwajima, Masaaki
Mendenhall, John M.
Parker, Patrick H.
Hubbard, Dusten D.
Hanka, Dakota C.
Abraham, Wickliffe C.
Harris, Kristen M.

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While astrocytes have long been recognized for their involvement in countless vital synaptic processes, acknowledgement of their active participation at the tripartite synapse has been comparatively recent. Astrocytes occupy largely non-overlapping domains, and perisynaptic astrocytic processes (PAPs) interdigitate the dense neuropil where they influence information processing. Previous studies of astrocyte nanoarchitecture show that astrocytes structurally associate with distinct synaptic clusters. Astrocyte calcium elevations that modulate neuronal activity may influence coordinated activation of synapses within such clusters. However, the astrocytic role in modulating synapse clusters during plasticity remains unknown. Here we leveraged 3D reconstruction from serial section electron microscopy (3DEM) and machine learning to investigate whether PAPs enhance synaptic plasticity in a cluster. An automated pipeline was developed to explore PAP morphological changes 30 minutes and 2 hours following long-term potentiation (LTP) or concurrent long-term depression (cLTD) induction, widely accepted cellular mechanisms of learning and memory. LTP and cLTD were induced in vivo in the rat dentate gyrus middle and outer molecular layers, respectively, via delta-burst stimulation of the medial perforant pathway. The contralateral hemispheres received medial path baseline stimulation to serve as within-subject controls. Moreover, serial section electron microscopy was used to capture high resolution images of the dentate gyrus neuropil. Preliminary analyses revealed that over 70% of dentate gyrus synapses exhibited PAP association at the axon-spine interface (ASI). The ASI length with astrocytic coverage scaled linearly with synapse size, thus maintaining proportional availability of astrocytic resources. In addition, the relationship between astrocytic contact length and individual synapse size was expanded in parallel with synapse growth during LTP. Synapses in closer proximity to each other were more similar in size during both control and LTP conditions. Thus, these early results suggest astrocytic processes respond to or coordinate changes in synapse size in synaptic clusters.


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