The role of astrocyte\u2010mediated plasticity in neural circuit development and function

Nelson A Perez-Catalan,Sarah D Ackerman,Chris Q Doe

doi:10.1186/s13064-020-00151-9

Abstract

Neuronal networks are capable of undergoing rapid structural and functional changes called plasticity, which are essential for shaping circuit function during nervous system development. These changes range from short-term modifications on the order of milliseconds, to long-term rearrangement of neural architecture that could last for the lifetime of the organism. Neural plasticity is most prominent during development, yet also plays a critical role during memory formation, behavior, and disease. Therefore, it is essential to define and characterize the mechanisms underlying the onset, duration, and form of plasticity. Astrocytes, the most numerous glial cell type in the human nervous system, are integral elements of synapses and are components of a glial network that can coordinate neural activity at a circuit-wide level. Moreover, their arrival to the CNS during late embryogenesis correlates to the onset of sensory-evoked activity, making them an interesting target for circuit plasticity studies. Technological advancements in the last decade have uncovered astrocytes as prominent regulators of circuit assembly and function. Here, we provide a brief historical perspective on our understanding of astrocytes in the nervous system, and review the latest advances on the role of astroglia in regulating circuit plasticity and function during nervous system development and homeostasis.

Highlights

Nervous system assembly requires precise coordination between the formation of millions of synapses and integration of these synapses into functional circuits
Astrocyte-derived synaptogenic and antisynaptogenic cues dynamically interact to finely tune synapse number during neural circuit assembly [8, 62]. As these pathways have been extensively covered elsewhere [8, 63], here we focus on Hevin and SPARC, which are essential for the generation of functional synapses during mammalian nervous system development, and regulate synapse plasticity [26]
A novel in vivo enzymatic assay defined a proteome for extracellular astrocyte-neuron junctions in the primary visual cortex (V1 cortex) and found that astrocytic Neuronal Cell Adhesion Molecule (NRCAM) binds to NRCAM-gephyrin complexes on postsynaptic neurons to induce the formation and function of inhibitory GABAergic synapses, with only minor effects on excitatory synapses [71]. These results identify a direct role for astrocytes in the control of excitatory and inhibitory synapse assembly and maturation in vivo, while displaying the heterogeneity of astroglial cues depending on the synapse subtype

Summary

Introduction

Nervous system assembly requires precise coordination between the formation of millions of synapses and integration of these synapses into functional circuits. As these pathways have been extensively covered elsewhere [8, 63], here we focus on Hevin and SPARC, which are essential for the generation of functional synapses during mammalian nervous system development, and regulate synapse plasticity (discussed below) [26]. Loss of MEGF10 in mouse results in a failure to refine retinogeniculate connections in the Astrocytes tune synapse function and synaptic plasticity The establishment of functional neuronal circuits does depend on early synaptogenic and pruning processes.

Results

Conclusion