Astrocytes as master modulators of neural networks: Synaptic functions and disease‐associated dysfunction of astrocytes

• Published in: Annals of the New York Academy of Sciences Vol. 1525; no. 1; pp. 41 - 60
• Main Authors: Stogsdill, Jeffrey A., Harwell, Corey C., Goldman, Steven A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2023
• Subjects: Astrocytes; Astrocytes - physiology; astrocytic heterogeneity; Brain; Central nervous system; Developmental plasticity; glia; Glial cells; Humans; Mental disorders; Modulators; Myelin; Myelin Sheath; Myelination; Neural networks; Neural Networks, Computer; Neural plasticity; Neuroglia; neurological disorders; Neuromodulation; Neurons - metabolism; Pathogenesis; Phenotypes; Substantia alba; synapse; Synaptogenesis; Therapeutic applications; white matter; white matter; astrocytes; synapse; glia; neurological disorders; astrocytic heterogeneity
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.15004

Astrocytes are the most abundant glial cell type in the central nervous system and are essential to the development, plasticity, and maintenance of neural circuits. Astrocytes are heterogeneous, with their diversity rooted in developmental programs modulated by the local brain environment. Astrocytes play integral roles in regulating and coordinating neural activity extending far beyond their metabolic support of neurons and other brain cell phenotypes. Both gray and white matter astrocytes occupy critical functional niches capable of modulating brain physiology on time scales slower than synaptic activity but faster than those adaptive responses requiring a structural change or adaptive myelination. Given their many associations and functional roles, it is not surprising that astrocytic dysfunction has been causally implicated in a broad set of neurodegenerative and neuropsychiatric disorders. In this review, we focus on recent discoveries concerning the contributions of astrocytes to the function of neural networks, with a dual focus on the contribution of astrocytes to synaptic development and maturation, and on their role in supporting myelin integrity, and hence conduction and its regulation. We then address the emerging roles of astrocytic dysfunction in disease pathogenesis and on potential strategies for targeting these cells for therapeutic purposes. Astrocytes play integral roles in the regulation and coordination of neural activity. These glial cells are a heterogeneous cell type, occupying functional niches throughout the brain. Not surprisingly, astrocytic dysfunction has been causally implicated in diverse neurological disorders. This review summarizes the current knowledge of astrocytes, with a dual focus on their contribution at synaptic and white matter sites, and addresses their niche‐specific association with disease pathogenesis.