Emerging roles of astrocytes in neural circuit development

Key Points Establishment of the correct number and type of synapses is essential for the formation of neural circuits and information processing in the brain. Despite the identification of a diverse range of neuronal mechanisms that regulate neural circuit formation, we are still far from fully understanding the processes involved. New evidence from rodent studies has revealed that astrocytes are key participants in neural circuit development. Astrocytes control synapse formation, maturation, function and elimination by a range of newly identified secreted and contact-mediated signals. Similarly, studies have revealed that human astrocytes can control synapse formation, suggesting that this feature is conserved across species. In fact, human astrocytes can induce the formation of a larger number of synapses than can rodent astrocytes. An understanding of the unique characteristics of human astrocytes might provide new insights into the greater capacity of the human brain to learn and adapt. Astrocytes are also increasingly being implicated in the pathophysiology of neurodevelopmental and neuropsychiatric disorders resulting from synapse defects. In particular, astrocyte dysfunction has been shown to contribute to the developmental defects in synapse development in Rett syndrome, fragile X syndrome and Down's syndrome. This surprising discovery that neurons rely on astrocytes to instruct the formation of their synapses leads to the possibility that astrocytes provide a layer of control that acts in parallel with, and interacts with, the neuronal processes that control circuit formation. A better understanding of the bidirectional signals between neurons and astrocytes should advance our knowledge of neuronal circuit development in health and disease. One of the roles of astrocytes in the brain is to regulate the formation, maturation, function and elimination of synapses and thereby to support the formation of appropriate neural circuits. Clarke and Barres review our current understanding of these vital processes and highlight unanswered questions for future research. Astrocytes are now emerging as key participants in many aspects of brain development, function and disease. In particular, new evidence shows that astrocytes powerfully control the formation, maturation, function and elimination of synapses through various secreted and contact-mediated signals. Astrocytes are also increasingly being implicated in the pathophysiology of many psychiatric and neu