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Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity.

Corty MM, Freeman MR - J. Cell Biol. (2013)

Bottom Line: Glia serve many important functions in the mature nervous system.In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development.Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurobiology, University of Massachusetts Medical School, Howard Hughes Medical Institute, Worcester, MA 01605.

ABSTRACT
Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

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Model of astrocyte–neuron interactions during synapse formation and maturation. (A) Astrocytes secrete several factors to promote structural synapse formation. Astrocytes secrete thrombospondins (TSPs), which act through α2–δ1 calcium channel subunit/gabapentin receptors to drive formation of structurally intact glutamatergic synapses. The exact mechanism by which TSP binding to α2–δ1 promotes adhesion and structural synapse formation is unknown. Astrocytes also secrete hevin and SPARC. Hevin also promotes structural synapse formation, whereas SPARC antagonizes this function. Competition between hevin and SPARC for a common unknown binding partner on neurons may explain the antagonism. The synapses formed in response to TSPs or hevin are structurally intact with docked vesicles and PSD-95 correctly localized; however, they lack surface expression of AMPARs at the postsynapse and are therefore not fully functional. (B) Other astrocyte-secreted factors influence surface expression and clustering of glutamatergic AMPARs. Glypicans secreted from astrocytes act through an unidentified receptor to promote surface expression and clustering of AMPARs during development. Activity can also induce astrocytes to secrete SPARC, which can perturb integrin interactions with surface AMPARs, leading to decreased surface expression of AMPARs in response to excess activity.
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fig3: Model of astrocyte–neuron interactions during synapse formation and maturation. (A) Astrocytes secrete several factors to promote structural synapse formation. Astrocytes secrete thrombospondins (TSPs), which act through α2–δ1 calcium channel subunit/gabapentin receptors to drive formation of structurally intact glutamatergic synapses. The exact mechanism by which TSP binding to α2–δ1 promotes adhesion and structural synapse formation is unknown. Astrocytes also secrete hevin and SPARC. Hevin also promotes structural synapse formation, whereas SPARC antagonizes this function. Competition between hevin and SPARC for a common unknown binding partner on neurons may explain the antagonism. The synapses formed in response to TSPs or hevin are structurally intact with docked vesicles and PSD-95 correctly localized; however, they lack surface expression of AMPARs at the postsynapse and are therefore not fully functional. (B) Other astrocyte-secreted factors influence surface expression and clustering of glutamatergic AMPARs. Glypicans secreted from astrocytes act through an unidentified receptor to promote surface expression and clustering of AMPARs during development. Activity can also induce astrocytes to secrete SPARC, which can perturb integrin interactions with surface AMPARs, leading to decreased surface expression of AMPARs in response to excess activity.

Mentions: In culture, the synapse-promoting effects of glia did not require physical contact between the glia and neurons, implicating secreted factors as the primary mediators of glia-induced synaptogenesis (Fig. 3). Fractionation of astrocyte-conditioned media (ACM) was used to identify thrombospondins (TSPs)—extracellular matrix proteins with known roles in cell adhesion—as key glial-derived synaptogenic factors (Fig. 3 A; Christopherson et al., 2005). Purified TSP-1 or TSP-2 mimicked ACM to promote structural synapse formation, whereas depleting TSP-2 from ACM abrogated its synaptogenic effects on cultured neurons. With a specific molecule in hand, researchers could now ask whether a glial-derived molecule was required for synaptogenesis in vivo. Christopherson et al. (2005) showed that TSPs are expressed in astrocytes in vivo when synapses are forming and colocalize with synapse-associated astrocyte processes. Importantly, mice mutant for both TSP-1 and TSP-2 had significantly fewer synapses than wild-type animals (∼40% reduction at P8), demonstrating a requirement for an astrocyte-derived factor for normal synapse development in vivo (Christopherson et al., 2005).


Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity.

Corty MM, Freeman MR - J. Cell Biol. (2013)

Model of astrocyte–neuron interactions during synapse formation and maturation. (A) Astrocytes secrete several factors to promote structural synapse formation. Astrocytes secrete thrombospondins (TSPs), which act through α2–δ1 calcium channel subunit/gabapentin receptors to drive formation of structurally intact glutamatergic synapses. The exact mechanism by which TSP binding to α2–δ1 promotes adhesion and structural synapse formation is unknown. Astrocytes also secrete hevin and SPARC. Hevin also promotes structural synapse formation, whereas SPARC antagonizes this function. Competition between hevin and SPARC for a common unknown binding partner on neurons may explain the antagonism. The synapses formed in response to TSPs or hevin are structurally intact with docked vesicles and PSD-95 correctly localized; however, they lack surface expression of AMPARs at the postsynapse and are therefore not fully functional. (B) Other astrocyte-secreted factors influence surface expression and clustering of glutamatergic AMPARs. Glypicans secreted from astrocytes act through an unidentified receptor to promote surface expression and clustering of AMPARs during development. Activity can also induce astrocytes to secrete SPARC, which can perturb integrin interactions with surface AMPARs, leading to decreased surface expression of AMPARs in response to excess activity.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3824021&req=5

fig3: Model of astrocyte–neuron interactions during synapse formation and maturation. (A) Astrocytes secrete several factors to promote structural synapse formation. Astrocytes secrete thrombospondins (TSPs), which act through α2–δ1 calcium channel subunit/gabapentin receptors to drive formation of structurally intact glutamatergic synapses. The exact mechanism by which TSP binding to α2–δ1 promotes adhesion and structural synapse formation is unknown. Astrocytes also secrete hevin and SPARC. Hevin also promotes structural synapse formation, whereas SPARC antagonizes this function. Competition between hevin and SPARC for a common unknown binding partner on neurons may explain the antagonism. The synapses formed in response to TSPs or hevin are structurally intact with docked vesicles and PSD-95 correctly localized; however, they lack surface expression of AMPARs at the postsynapse and are therefore not fully functional. (B) Other astrocyte-secreted factors influence surface expression and clustering of glutamatergic AMPARs. Glypicans secreted from astrocytes act through an unidentified receptor to promote surface expression and clustering of AMPARs during development. Activity can also induce astrocytes to secrete SPARC, which can perturb integrin interactions with surface AMPARs, leading to decreased surface expression of AMPARs in response to excess activity.
Mentions: In culture, the synapse-promoting effects of glia did not require physical contact between the glia and neurons, implicating secreted factors as the primary mediators of glia-induced synaptogenesis (Fig. 3). Fractionation of astrocyte-conditioned media (ACM) was used to identify thrombospondins (TSPs)—extracellular matrix proteins with known roles in cell adhesion—as key glial-derived synaptogenic factors (Fig. 3 A; Christopherson et al., 2005). Purified TSP-1 or TSP-2 mimicked ACM to promote structural synapse formation, whereas depleting TSP-2 from ACM abrogated its synaptogenic effects on cultured neurons. With a specific molecule in hand, researchers could now ask whether a glial-derived molecule was required for synaptogenesis in vivo. Christopherson et al. (2005) showed that TSPs are expressed in astrocytes in vivo when synapses are forming and colocalize with synapse-associated astrocyte processes. Importantly, mice mutant for both TSP-1 and TSP-2 had significantly fewer synapses than wild-type animals (∼40% reduction at P8), demonstrating a requirement for an astrocyte-derived factor for normal synapse development in vivo (Christopherson et al., 2005).

Bottom Line: Glia serve many important functions in the mature nervous system.In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development.Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurobiology, University of Massachusetts Medical School, Howard Hughes Medical Institute, Worcester, MA 01605.

ABSTRACT
Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

Show MeSH
Related in: MedlinePlus