Chemico-genetic discovery of astrocytic control of inhibition in vivo

Takano, Tetsuya; Wallace, John T; Baldwin, Katherine T.; Purkey, Alicia; Uezu, Akiyoshi; Courtland, Jamie L; Soderblom, Erik J.; Shimogori, Tomomi; Maness, Patricia F.; Eroğlu, Çağla; Soderling, Scott H.

doi:10.1038/s41586-020-2926-0

Cited by 171 publications

(167 citation statements)

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“…Because these proteins are not known to physically interact, it remains to be seen how Hevin and SPARC function together to tune synapse number in vivo [26]. More recently, 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]. Together, these results identify a direct role for astrocytes in the control of excitatory and inhibitory synapse assembly and maturation in vivo, while also displaying the heterogeneity of astroglial cues depending on the synapse subtype.…”

Section: Astrocytes In Synaptogenesismentioning

confidence: 99%

The role of astrocyte‐mediated plasticity in neural circuit development and function

2021

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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.

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Section: Astrocytes In Synaptogenesismentioning

confidence: 99%

The role of astrocyte‐mediated plasticity in neural circuit development and function

2021

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“…Our recent study on synaptic plasticity is one example (Henneberger et al, 2020), in which results from volume fraction measurements were then further investigated using STED and electron microscopy. Other options are techniques for locating neuron-astrocyte interaction sites using proximity assays (Octeau et al, 2018) and for identifying the proteins enriched at such contact sites (Takano et al, 2020).…”

Section: Capturing Heterogeneity and Developmental Changes Of Astrocyte Morphologymentioning

confidence: 99%

Heterogeneity and Development of Fine Astrocyte Morphology Captured by Diffraction-Limited Microscopy

Minge

Domingos

Unichenko

et al. 2021

Front. Cell. Neurosci.

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The fine processes of single astrocytes can contact many thousands of synapses whose function they can modulate through bi-directional signaling. The spatial arrangement of astrocytic processes and neuronal structures is relevant for such interactions and for the support of neuronal signaling by astrocytes. At the same time, the geometry of perisynaptic astrocyte processes is variable and dynamically regulated. Studying these fine astrocyte processes represents a technical challenge, because many of them cannot be fully resolved by diffraction-limited microscopy. Therefore, we have established two indirect parameters of astrocyte morphology, which, while not fully resolving local geometry by design, provide statistical measures of astrocyte morphology: the fraction of tissue volume that astrocytes occupy and the density of resolvable astrocytic processes. Both are straightforward to obtain using widely available microscopy techniques. We here present the approach and demonstrate its robustness across various experimental conditions using mainly two-photon excitation fluorescence microscopy in acute slices and in vivo as well as modeling. Using these indirect measures allowed us to analyze the morphology of relatively large populations of astrocytes. Doing so we captured the heterogeneity of astrocytes within and between the layers of the hippocampal CA1 region and the developmental profile of astrocyte morphology. This demonstrates that volume fraction (VF) and segment density are useful parameters for describing the structure of astrocytes. They are also suitable for online monitoring of astrocyte morphology with widely available microscopy techniques.

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“…In particular, astrocytes promote synapse formation through the secretion of synaptogenic factors (e.g. SPARCL1, thrombospondins, ApoE, Chordin-like 1, TGF, and glypicans) [7][8][9][10][11][12] and via contactdependent mechanisms [13][14][15] . However, the role of astrocytes in synaptogenesis and synaptic pruning does not readily explain why they make persistent intercellular junctions with synapses well after their formation and into adulthood.…”

mentioning

confidence: 99%

Compartment-Specific Neurexin Nanodomains Orchestrate Tripartite Synapse Assembly

Trotter

Dargaei

Sclip

et al. 2020

Preprint

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At tripartite synapses, astrocytes surround synaptic contacts, but how astrocytes contribute to the assembly and function of synapses remains unclear. Here we show that neurexin-1α, a presynaptic adhesion molecule that controls synapse properties, is also abundantly expressed by astrocytes. Strikingly, astrocytic neurexin-1α, but not neuronal neurexin-1α, is highly modified by heparan sulfate. Moreover, astrocytic neurexin-1α is uniquely alternatively spliced and invariably contains an insert in splice-site #4, thereby restricting the range of ligands to which it binds. Deletion of neurexin-1 from astrocytes or neurons does not alter synapse numbers or synapse ultrastructure, but differentially impairs synapse function. At hippocampal Schaffer-collateral synapses, neuronal neurexin-1 is essential for normal NMDA-receptor-mediated synaptic responses, whereas astrocytic neurexin-1 is required for normal AMPA-receptor-mediated synaptic responses and for long-term potentiation of these responses. Thus, astrocytes directly shape synapse properties via a neurexin-1-dependent mechanism that involves a specific molecular program distinct from that of neuronal neurexin-1.

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Chemico-genetic discovery of astrocytic control of inhibition in vivo

Cited by 171 publications

References 50 publications

The role of astrocyte‐mediated plasticity in neural circuit development and function

The role of astrocyte‐mediated plasticity in neural circuit development and function

Heterogeneity and Development of Fine Astrocyte Morphology Captured by Diffraction-Limited Microscopy

Compartment-Specific Neurexin Nanodomains Orchestrate Tripartite Synapse Assembly

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