Activity-Dependent Structural and Functional Plasticity of Astrocyte-Neuron Interactions

Abstract

Observations from different brain areas have established that the adult nervous system can undergo significant experience-related structural changes throughout life. Less familiar is the notion that morphological plasticity affects not only neurons but glial cells as well. Yet there is abundant evidence showing that astrocytes, the most numerous cells in the mammalian brain, are highly mobile. Under physiological conditions as different as reproduction, sensory stimulation, and learning, they display a remarkable structural plasticity, particularly conspicuous at the level of their lamellate distal processes that normally ensheath all portions of neurons. Distal astrocytic processes can undergo morphological changes in a matter of minutes, a remodeling that modifies the geometry and diffusion properties of the extracellular space and relationships with adjacent neuronal elements, especially synapses. Astrocytes respond to neuronal activity via ion channels, neurotransmitter receptors, and transporters on their processes; they transmit information via release of neuroactive substances. Where astrocytic processes are mobile then, astrocytic-neuronal interactions become highly dynamic, a plasticity that has important functional consequences since it modifies extracellular ionic homeostasis, neurotransmission, gliotransmission, and ultimately neuronal function at the cellular and system levels. Although a complete picture of intervening cellular mechanisms is lacking, some have been identified, notably certain permissive molecular factors common to systems capable of remodeling (cell surface and extracellular matrix adhesion molecules, cytoskeletal proteins) and molecules that appear specific to each system (neuropeptides, neurotransmitters, steroids, growth factors) that trigger or reverse the morphological changes.

Astrocytic glutamate transport regulates a Drosophila CNS synapse that lacks astrocyte ensheathment

“…At one extreme, cerebellar synapses formed by climbing fibers in rodents show an average degree of enwrapping around 87% (Xu-Friedman et al, 2001), whereas estimates of degree of enwrapping in the neocortex are lower and suggest that ensheathment is rare (<10% of synapses), and contact with the dendritic spine (but not the axon-spine interfaces) dominates (70%) (Genoud et al, 2006). The significance of these differences is poorly understood, but may involve 1) the stability and maturity of the synapse (Nishida and Okabe, 2007;Medvedev et al, 2014), 2) patterns of neuronal connectivity, such that some areas are by design more disposed to transmitter spillover (Bernardinelli et al, 2014), and 3) dynamic astrocytic process extension and retraction in response to neuronal activity and hormonal changes (Theodosis et al, 2008). These distances, however, should be viewed as relative, since these methods do not account for the actual diffusion pathway, which is tortuous, and all measurements taken from chemically-fixed EM preparations are subject to non-uniform shrinkage, making astrocytes appear to be located closer to synapses than they are in vivo (Korogod et al, 2015).…”

Stochastic nanoroughness modulates neuron–astrocyte interactions and function via mechanosensing cation channels

“…In the context of neuronal development and neurophysiology, astrocytes have an established role in maintaining neuronal function. They form a vast network that provides the physical and biochemical matrix over which neurons thrive and function (15,16). The plasticity found in the brain can be attributed in part to the morphological changes that occur in astrocyte processes that can not only alter the geometry of the neuronal environment but also induce dynamic changes in astrocyte-neuron interactions affecting neurotransmission, signal gradients, and the relationship between synapses (15).…”

Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors

“…At the ultrastructural level, the PAPs, although abundant in the neuropil, specifically prefer contacting synapses and dendrites versus axons (4). The synaptic wrapping is highly dynamic (5-9) and also activity-dependent even in the context of physiological functions, such as motor learning, daily fluctuations of the circadian clock, lactation, parturition, or dehydration (10)(11)(12)(13)(14)(15). Here, we asked two questions about the structural basis of glia-synaptic interaction: What is the stimulus for PAP plasticity, and what are the intracellular mechanisms accomplishing the motility and the formation of the PAP?…”