Astrocytes shape the plastic response of adult cortical neurons to vision loss

Abstract

 Visual deprivation induces a fast and persistent upregulation of Aldh1l1-positive astrocytes  Acute fluorocitrate-induced silencing of astrocytes impedes neuronal reactivation  G i but not G q GPCR astrocyte activation promotes adult cortical plasticity Word count by section: Abstract (243), Introduction (520), Materials and Methods (2732), Results (2192), Discussion (1946), References (2056), Figure legends (1170)

Star power: the emerging role of astrocytes as neuronal partners during cortical plasticity

“…There are an increasing number of studies documenting that astrocytes play key roles in all aspects of circuit remodeling across plasticity paradigms involving vision loss [ 2 •• , 5 •• ]. The introduction of powerful genetic tools [ 3 ] has permitted detailed mechanistic studies of the roles played by astrocytes in CNS development and response to injury, which largely parallel those needed during adult plasticity.…”

“…The introduction of powerful genetic tools [ 3 ] has permitted detailed mechanistic studies of the roles played by astrocytes in CNS development and response to injury, which largely parallel those needed during adult plasticity. Our own data, unambiguously demonstrating that astrocytes are essential for visual cortex reorganization in adults [ 5 •• ], has led us to develop a conceptual framework for the role of astrocytes in plasticity, which can be experimentally tested in the coming years. No doubt, as we learn more about how these cells function, new questions concerning their role(s) in plasticity will arise.…”

“…How is the injury response affected by aging? How does chemogenetic activation of astrocytes boost plasticity [ 5 •• , 61 ]? Can these insights be harnessed for therapeutic purposes?…”

“…This increased neuronal activity is initially driven by open-eye responses, followed by a later phase of cross-modal plasticity driven by whisker-inputs. This neuronal reactivation can be enhanced (orange) by CNO-based activation of astrocytes in the sensory deprived cortex, following vector-based delivery of a G i -coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) [ 5 •• ]. …”

“…Such circuit remodeling remains possible in adult animals, albeit reduced in strength, with astrocyte-specific activation recently shown to enhance deprivation-induced plasticity in visual cortex [ 5 •• ] ( Figure 1 b). Furthermore, it appears that, just like neurons, astrocytes recapitulate functions from early post-natal development to drive this process, as transplantation of young post-natal astrocytes into adult animals reinstates high levels of plasticity in the sensory cortex [ 2 •• ] ( Figure 1 a).…”