Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses

Abstract

Accumulating evidence is redefining the importance of neuron-glial interactions at synapses in the CNS. Astrocytes form "tripartite" complexes with presynaptic and postsynaptic structures and regulate synaptic transmission and plasticity. Despite our understanding of the importance of neuron-glial relationships in physiological contexts, little is known about the structural interplay between astrocytes and synapses. In the past, this has been difficult to explore because studies have been hampered by the lack of a system that preserves complex neuron-glial relationships observed in the brain. Here we present a system that can be used to characterize the intricate relationship between astrocytic processes and synaptic structures in situ using organotypic hippocampal slices, a preparation that retains the three-dimensional architecture of astrocyte-synapse interactions. Using time-lapse confocal imaging, we demonstrate that astrocytes can rapidly extend and retract fine processes to engage and disengage from motile postsynaptic dendritic spines. Surprisingly, astrocytic motility is, on average, higher than its dendritic spine counterparts and likely relies on actin-based cytoskeletal reorganization. Changes in astrocytic processes are typically coordinated with changes in spines, and astrocyte-spine interactions are stabilized at larger spines. Our results suggest that dynamic structural changes in astrocytes help control the degree of neuron-glial communication at hippocampal synapses.

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

“…PAPs are highly motile structures, to an even higher degree than dendritic spines [21]. Our data suggest that PAP motility is regulated by synaptically released glutamate through activation of PAP mGluRs and the generation of Ca 2+ transients.…”

“…It was characterized by continuous movements around spines over the time course of minutes ( Figure 1C). These movements were quantified using a motility index (MI; Figure S2), similar to previously published methods [21,30]. The PAP MI varied between spines ( Figures 1D and 1E) but was inversely correlated with the initial PAP coverage of the spine ( Figure 1D).…”

“…Yet another intriguing property of perisynaptic astrocytic processes is their morphologically highly plastic nature [21]. Perisynaptic astrocytic processes (PAPs) express specific acting-binding proteins [22], and their plasticity may result in variable degrees of pre-and postsynaptic coverage of the synapse [23][24][25].…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…This cascade in turn might influence actin dynamics and hence filopodia growth, as suggested in studies using calcium uncaging in astrocyte cultures and genetic attenuation of IP 3 signaling in vivo (Molotkov et al, 2013; Tanaka et al, 2013). PAPs do contain actin as their cytoskeleton basis (Safavi‐Abbasi et al, 2001), and inhibition of actin polymerization disables PAP mobility (Haber et al, 2006). Astrocytic filopodia outgrowth does not require new synthesis or degradation but rather a redistribution of existing cytoskeletal proteins (Safavi‐Abbasi et al, 2001).…”

Synaptic and extrasynaptic traces of long-term memory: the ID molecule theory

“…In the case of neurons, the time of noticeable change is measured in hours or days (Woolley et al, 1990;Kirov et al, 1999;Stettler et al, 2006); in the case of astrocytes, it is measured in minutes (Haber et al, 2006). There is evidence, from time-lapse confocal imaging (Haber et al, 2006), that astrocytic processes a small distance away from a dendritic spine, but not directly apposed to it, can grow several microns in a few minutes, until they are in direct apposition to it, and the pictures indicate that corresponding neuronal elements are much less motile. The slower rate of synaptic changes has been directly verified, also through time-lapse confocal imaging, by Stettler et al (2006).…”