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Spatial constraints dictate glial territories at murine neuromuscular junctions.

Brill MS, Lichtman JW, Thompson W, Zuo Y, Misgeld T - J. Cell Biol. (2011)

Bottom Line: Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle.The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects.In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Integrated Protein Science Munich at the Institute of Neuroscience, Technische Universität München, 80802 Munich, Germany.

ABSTRACT
Schwann cells (SCs), the glial cells of the peripheral nervous system, cover synaptic terminals, allowing them to monitor and modulate neurotransmission. Disruption of glial coverage leads to axon degeneration and synapse loss. The cellular mechanisms that establish and maintain this coverage remain largely unknown. To address this, we labeled single SCs and performed time-lapse imaging experiments. Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle. The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects. In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

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Chronic in vivo imaging of mature terminal SCs. (A and B) In vivo images of the same NMJs in the sternomastoid muscle of living SC-GFP mice obtained several weeks apart (interval 2.2 ± 1.0 mo; age at onset of imaging: 4.7 ± 1.1 mo, n = 53 adult NMJs, 10 mice). AChRs were labeled with a nonblocking concentration of BTX (red). Axons are labeled with thy1-CFP (green). (A) Addition of terminal SCs. NMJ with two terminal SCs at 6.5 mo and four terminal SCs at 10 mo. (B) Territory reconstruction of individual terminal SCs from A based on photobleaching in the living animal (bleach 1–3) reveals two new terminal SCs with substantial synaptic territory. (C) Translocation of terminal SCs. NMJ at 2.5 mo with five terminal SCs, one of which translocates across the synapse during the following 3.5 mo (orange arrowheads). Bars, 5 µm.
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fig3: Chronic in vivo imaging of mature terminal SCs. (A and B) In vivo images of the same NMJs in the sternomastoid muscle of living SC-GFP mice obtained several weeks apart (interval 2.2 ± 1.0 mo; age at onset of imaging: 4.7 ± 1.1 mo, n = 53 adult NMJs, 10 mice). AChRs were labeled with a nonblocking concentration of BTX (red). Axons are labeled with thy1-CFP (green). (A) Addition of terminal SCs. NMJ with two terminal SCs at 6.5 mo and four terminal SCs at 10 mo. (B) Territory reconstruction of individual terminal SCs from A based on photobleaching in the living animal (bleach 1–3) reveals two new terminal SCs with substantial synaptic territory. (C) Translocation of terminal SCs. NMJ at 2.5 mo with five terminal SCs, one of which translocates across the synapse during the following 3.5 mo (orange arrowheads). Bars, 5 µm.

Mentions: Our ex vivo observations of limited adult SC dynamism over periods of hours did not rule out that bigger changes would arise over months (Livet et al., 2007). To address this possibility, we performed long-term observations of single NMJs using repetitive in vivo imaging in the sternomastoid muscle (see Materials and methods; Fig. 3; Lichtman et al., 1987; Zuo et al., 2004). Indeed, we found significant long-term remodeling of terminal SCs in the adult. Out of 53 adult NMJs (n = 10 mice) followed over several weeks, more than one third showed obvious changes in terminal SC position or number, such as translocation (13%), disappearance (15%), or addition (15%). Sequential bleaching further revealed that newly added terminal SCs obtained substantial synaptic territory from their neighbors (Fig. 3 B).


Spatial constraints dictate glial territories at murine neuromuscular junctions.

Brill MS, Lichtman JW, Thompson W, Zuo Y, Misgeld T - J. Cell Biol. (2011)

Chronic in vivo imaging of mature terminal SCs. (A and B) In vivo images of the same NMJs in the sternomastoid muscle of living SC-GFP mice obtained several weeks apart (interval 2.2 ± 1.0 mo; age at onset of imaging: 4.7 ± 1.1 mo, n = 53 adult NMJs, 10 mice). AChRs were labeled with a nonblocking concentration of BTX (red). Axons are labeled with thy1-CFP (green). (A) Addition of terminal SCs. NMJ with two terminal SCs at 6.5 mo and four terminal SCs at 10 mo. (B) Territory reconstruction of individual terminal SCs from A based on photobleaching in the living animal (bleach 1–3) reveals two new terminal SCs with substantial synaptic territory. (C) Translocation of terminal SCs. NMJ at 2.5 mo with five terminal SCs, one of which translocates across the synapse during the following 3.5 mo (orange arrowheads). Bars, 5 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3198169&req=5

fig3: Chronic in vivo imaging of mature terminal SCs. (A and B) In vivo images of the same NMJs in the sternomastoid muscle of living SC-GFP mice obtained several weeks apart (interval 2.2 ± 1.0 mo; age at onset of imaging: 4.7 ± 1.1 mo, n = 53 adult NMJs, 10 mice). AChRs were labeled with a nonblocking concentration of BTX (red). Axons are labeled with thy1-CFP (green). (A) Addition of terminal SCs. NMJ with two terminal SCs at 6.5 mo and four terminal SCs at 10 mo. (B) Territory reconstruction of individual terminal SCs from A based on photobleaching in the living animal (bleach 1–3) reveals two new terminal SCs with substantial synaptic territory. (C) Translocation of terminal SCs. NMJ at 2.5 mo with five terminal SCs, one of which translocates across the synapse during the following 3.5 mo (orange arrowheads). Bars, 5 µm.
Mentions: Our ex vivo observations of limited adult SC dynamism over periods of hours did not rule out that bigger changes would arise over months (Livet et al., 2007). To address this possibility, we performed long-term observations of single NMJs using repetitive in vivo imaging in the sternomastoid muscle (see Materials and methods; Fig. 3; Lichtman et al., 1987; Zuo et al., 2004). Indeed, we found significant long-term remodeling of terminal SCs in the adult. Out of 53 adult NMJs (n = 10 mice) followed over several weeks, more than one third showed obvious changes in terminal SC position or number, such as translocation (13%), disappearance (15%), or addition (15%). Sequential bleaching further revealed that newly added terminal SCs obtained substantial synaptic territory from their neighbors (Fig. 3 B).

Bottom Line: Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle.The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects.In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Integrated Protein Science Munich at the Institute of Neuroscience, Technische Universität München, 80802 Munich, Germany.

ABSTRACT
Schwann cells (SCs), the glial cells of the peripheral nervous system, cover synaptic terminals, allowing them to monitor and modulate neurotransmission. Disruption of glial coverage leads to axon degeneration and synapse loss. The cellular mechanisms that establish and maintain this coverage remain largely unknown. To address this, we labeled single SCs and performed time-lapse imaging experiments. Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle. The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects. In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

Show MeSH
Related in: MedlinePlus