Structural and Functional Plasticity of Astrocyte Processes and Dendritic Spine Interactions

Abstract

Experience-dependent plasticity of synaptic transmission, which represents the cellular basis of learning, is accompanied by morphological changes in dendritic spines. Astrocytic processes are intimately associated with synapses, structurally enwrapping and functionally interacting with dendritic spines and synaptic terminals by responding to neurotransmitters and by releasing gliotransmitters that regulate synaptic function. While studies on structural synaptic plasticity have focused on neuronal elements, the structural-functional plasticity of astrocyte-neuron relationships remains poorly known. Here we show that stimuli inducing hippocampal synaptic LTP enhance the motility of synapse-associated astrocytic processes. This motility increase is relatively rapid, starting Ͻ5 min after the stimulus, and reaching a maximum in 20 -30 min (t (1/2) ϭ 10.7 min). It depends on presynaptic activity and requires G-protein-mediated Ca 2ϩ elevations in astrocytes. The structural remodeling is accompanied by changes in the ability of astrocytes to regulate synaptic transmission. Sensory stimuli that increase astrocyte Ca 2ϩ also induce similar plasticity in mouse somatosensory cortex in vivo. Therefore, structural relationships between astrocytic processes and dendritic spines undergo activity-dependent changes with metaplasticity consequences on synaptic regulation. These results reveal novel forms of synaptic plasticity based on structural-functional changes of astrocyte-neuron interactions.

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…Very fine, and apparently highly mobile, astrocytic processes have been reported in organotypic brain slices using a membrane‐bound GFP (Benediktsson et al, 2005). Furthermore, co‐labeling of dendritic spines and PAPs in hippocampal (Halassa et al, 2007a; Perez‐Alvarez et al, 2014; Verbich et al, 2012) and cerebellar slices (Lippman Bell et al, 2010; Lippman et al, 2008) as well as in vivo (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014) suggested that PAPs are highly dynamic structures that engage and disengage with dendritic spines, also responding to the induction of synaptic plasticity (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014). …”

“…Astrocytes (and probably PAPs) express both, AMPARs and mGluRs (see above) and both receptor types might be involved in astrocytic filopodia outgrowth (Bernardinelli et al, 2014a). More recently, the induction of LTP in hippocampal slices and whisker stimulation has led to measureable PAP displacement in the hippocampus and the barrel cortex, respectively (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014). It was suggested that PAP motility is (a) synapse‐specific, (b) neuronal activity‐dependent (application of TTX blocks PAP movement), (c) mGluR‐dependent, (d) Ca 2+ ‐dependent, and (e) IP 3 ‐dependent (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014).…”

“…More recently, the induction of LTP in hippocampal slices and whisker stimulation has led to measureable PAP displacement in the hippocampus and the barrel cortex, respectively (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014). It was suggested that PAP motility is (a) synapse‐specific, (b) neuronal activity‐dependent (application of TTX blocks PAP movement), (c) mGluR‐dependent, (d) Ca 2+ ‐dependent, and (e) IP 3 ‐dependent (Bernardinelli et al, 2014b; Perez‐Alvarez et al, 2014). These observations raise an intriguing question of whether there are organizational principles for the presence and shape of PAPs depending on the brain area, synaptic types and species (Reichenbach et al, 2010).…”

Cellular diversity of the somatosensory cortical map plasticity

“…EDP requires the interaction of the numerous different cell types that exist in the brain, from excitatory (Allen et al, 2003) and inhibitory (Foeller et al, 2005) neurons to glia (Perez-Alvarez et al, 2014) and even the epithelial and muscle cells of blood vessels (Lacoste et al, 2014;Whiteus et al, 2014). A major unanswered question is how the vastly diverse cortical cellular population orchestrates EDP and which of the molecules that underlie it are common across (all) cell types and which are critical to a select few.…”

Suppression of SNARE‐dependent exocytosis in retinal glial cells and its effect on ischemia‐induced neurodegeneration

“…The physiologic relevance of this process is debated: it may contribute to glial volume regulation (Slezak et al, 2012) and modulate neuronal activity (Araque et al, 2014; Chen et al, 2012; Perez‐Alvarez, Navarrete, Covelo, Martin, & Araque, 2014; Takata et al, 2011). Here, we studied the contribution of glial SNARE‐dependent exocytosis to neurodegeneration in the retina.…”