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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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SC segregation is activity independent but requires axonal presence. (A) Block of neurotransmission by BoTX treatment did not alter morphology of SCs after 3–4 d. Axon (green), synaptic gutter (BTX [red]) and SCs (white [left] and individually pseudocolored [right]). (B–E) Mice with delayed axon fragmentation (ΔNLS) do not show SC intermingling for up to 2 d after transection. (B) Quantification of area overlap after axotomy in ΔNLS mice (mean of SCs + SEM; *, P < 0.01 using a t test; ΔNLS cut, n = 36 SC pairs, three triangularis sterni muscles; ΔNLS uncut, n = 20 SC pairs, three triangularis sterni muscles; WT cut, n = 31 SC pairs, seven triangularis sterni muscles). (C) Single-cell labeling of an NMJ 2 d after axotomy shows segregated SCs and a preserved axon (D) on top of the synaptic gutter (BTX). Despite preserved axon continuity, local axon atrophy was observed (orange arrowheads in D). (E) Time-lapse microscopy over a period of >2 h demonstrates the lack of terminal SC dynamism at axotomized ΔNLS NMJs (shown in the area boxed in C). The timers shown represent hours/minutes. Bars, 5 µm.
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fig8: SC segregation is activity independent but requires axonal presence. (A) Block of neurotransmission by BoTX treatment did not alter morphology of SCs after 3–4 d. Axon (green), synaptic gutter (BTX [red]) and SCs (white [left] and individually pseudocolored [right]). (B–E) Mice with delayed axon fragmentation (ΔNLS) do not show SC intermingling for up to 2 d after transection. (B) Quantification of area overlap after axotomy in ΔNLS mice (mean of SCs + SEM; *, P < 0.01 using a t test; ΔNLS cut, n = 36 SC pairs, three triangularis sterni muscles; ΔNLS uncut, n = 20 SC pairs, three triangularis sterni muscles; WT cut, n = 31 SC pairs, seven triangularis sterni muscles). (C) Single-cell labeling of an NMJ 2 d after axotomy shows segregated SCs and a preserved axon (D) on top of the synaptic gutter (BTX). Despite preserved axon continuity, local axon atrophy was observed (orange arrowheads in D). (E) Time-lapse microscopy over a period of >2 h demonstrates the lack of terminal SC dynamism at axotomized ΔNLS NMJs (shown in the area boxed in C). The timers shown represent hours/minutes. Bars, 5 µm.

Mentions: When neurotransmission was blocked, even if this blockade lasted for at least 24 h (and up to 3 d), no changes in morphological parameters of SCs were apparent (Fig. 8 A), including number, length, and overlap of terminal SC processes, which remained unchanged (BoTX: 4.7 ± 0.5 processes/cell, 14.1 ± 1.2 µm/process, 8.2 ± 2.3% overlap, n = 15 SCs vs. control: 4.4 ± 0.3 processes/cell, 13.9 ± 0.8 µm/process, 7.9 ± 2.0% overlap, n = 27 SCs; P > 0.6 for all using a t test).


Spatial constraints dictate glial territories at murine neuromuscular junctions.

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

SC segregation is activity independent but requires axonal presence. (A) Block of neurotransmission by BoTX treatment did not alter morphology of SCs after 3–4 d. Axon (green), synaptic gutter (BTX [red]) and SCs (white [left] and individually pseudocolored [right]). (B–E) Mice with delayed axon fragmentation (ΔNLS) do not show SC intermingling for up to 2 d after transection. (B) Quantification of area overlap after axotomy in ΔNLS mice (mean of SCs + SEM; *, P < 0.01 using a t test; ΔNLS cut, n = 36 SC pairs, three triangularis sterni muscles; ΔNLS uncut, n = 20 SC pairs, three triangularis sterni muscles; WT cut, n = 31 SC pairs, seven triangularis sterni muscles). (C) Single-cell labeling of an NMJ 2 d after axotomy shows segregated SCs and a preserved axon (D) on top of the synaptic gutter (BTX). Despite preserved axon continuity, local axon atrophy was observed (orange arrowheads in D). (E) Time-lapse microscopy over a period of >2 h demonstrates the lack of terminal SC dynamism at axotomized ΔNLS NMJs (shown in the area boxed in C). The timers shown represent hours/minutes. Bars, 5 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig8: SC segregation is activity independent but requires axonal presence. (A) Block of neurotransmission by BoTX treatment did not alter morphology of SCs after 3–4 d. Axon (green), synaptic gutter (BTX [red]) and SCs (white [left] and individually pseudocolored [right]). (B–E) Mice with delayed axon fragmentation (ΔNLS) do not show SC intermingling for up to 2 d after transection. (B) Quantification of area overlap after axotomy in ΔNLS mice (mean of SCs + SEM; *, P < 0.01 using a t test; ΔNLS cut, n = 36 SC pairs, three triangularis sterni muscles; ΔNLS uncut, n = 20 SC pairs, three triangularis sterni muscles; WT cut, n = 31 SC pairs, seven triangularis sterni muscles). (C) Single-cell labeling of an NMJ 2 d after axotomy shows segregated SCs and a preserved axon (D) on top of the synaptic gutter (BTX). Despite preserved axon continuity, local axon atrophy was observed (orange arrowheads in D). (E) Time-lapse microscopy over a period of >2 h demonstrates the lack of terminal SC dynamism at axotomized ΔNLS NMJs (shown in the area boxed in C). The timers shown represent hours/minutes. Bars, 5 µm.
Mentions: When neurotransmission was blocked, even if this blockade lasted for at least 24 h (and up to 3 d), no changes in morphological parameters of SCs were apparent (Fig. 8 A), including number, length, and overlap of terminal SC processes, which remained unchanged (BoTX: 4.7 ± 0.5 processes/cell, 14.1 ± 1.2 µm/process, 8.2 ± 2.3% overlap, n = 15 SCs vs. control: 4.4 ± 0.3 processes/cell, 13.9 ± 0.8 µm/process, 7.9 ± 2.0% overlap, n = 27 SCs; P > 0.6 for all using a t test).

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