Visualizing synapse formation in arborizing optic axons in vivo: dynamics and modulation by BDNF

Drosophila Connectin (CON) is a cell surface protein of the leucine-rich repeat family. During the formation of neuromuscular connectivity, CON is expressed on the surface of a subset of embryonic muscles and on the growth cones and axons of the motoneurons that innervate these muscles, including primarily SNa motoneurons and their synaptic targets (lateral muscles). In vitro, CON can mediate homophilic cell adhesion. In this study, we generated transgenic lines that ectopically expressed CON on all muscles. In the transformant embryos and larvae, SNa motoneurons often inappropriately innervated a neighboring non-target muscle (muscle 12) that ectopically expressed CON. Furthermore, the ectopic synapse formation was dependent on the endogenous CON expression on the SNa motoneurons. These results show that CON can function as an attractive and homophilic target recognition molecule in vivo.

Download Full-text

Syncrip/hnRNP Q is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation

The Journal of Cell Biology ◽

10.1083/jcb.201903135 ◽

2020 ◽

Vol 219 (3) ◽

Cited By ~ 4

Author(s):

Joshua Titlow ◽

Francesca Robertson ◽

Aino Järvelin ◽

David Ish-Horowicz ◽

Carlas Smith ◽

...

Keyword(s):

Single Molecule ◽

Posttranscriptional Regulation ◽

Rna Binding ◽

Synapse Formation ◽

Long Distance ◽

Key Factor ◽

Larval Neuromuscular Junction ◽

Rnp Granules ◽

Activity Dependent

Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganization at new synapses, requiring posttranscriptional regulation of localized mRNA a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organizes actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is poorly understood. Here, we show that activity-dependent accumulation of Msp300 in the postsynaptic compartment of the Drosophila larval neuromuscular junction is regulated by the conserved RNA binding protein Syncrip/hnRNP Q. Syncrip (Syp) binds to msp300 transcripts and is essential for plasticity. Single-molecule imaging shows that msp300 is associated with Syp in vivo and forms ribosome-rich granules that contain the translation factor eIF4E. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these particles facilitate translation. These results introduce Syp as an important early acting activity-dependent regulator of a plasticity gene that is strongly associated with human ataxias.

Download Full-text

Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus

10.1101/515759 ◽

2019 ◽

Cited By ~ 1

Author(s):

Felix C. Nebeling ◽

Stefanie Poll ◽

Lena C. Schmid ◽

Manuel Mittag ◽

Julia Steffen ◽

...

Keyword(s):

Neuronal Activity ◽

Dendritic Spines ◽

Synapse Formation ◽

Brain Parenchyma ◽

Two Photon ◽

Contact Rates ◽

Health And Disease ◽

The Impact ◽

The Brain

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

Download Full-text

Quantification of synapse formation and maintenance in vivo in the absence of synaptic release

Neuroscience ◽

10.1016/j.neuroscience.2004.03.027 ◽

2004 ◽

Vol 126 (1) ◽

pp. 115-126 ◽

Cited By ~ 35

Author(s):

J. Bouwman ◽

A.S. Maia ◽

P.G. Camoletto ◽

G. Posthuma ◽

E.W. Roubos ◽

...

Keyword(s):

Synapse Formation ◽

Synaptic Release

Download Full-text

Engineered synaptic tools reveal localized cAMP signaling in synapse assembly

The Journal of Cell Biology ◽

10.1083/jcb.202109111 ◽

2021 ◽

Vol 221 (2) ◽

Author(s):

Richard Sando ◽

Milan Lyndie Ho ◽

Xinran Liu ◽

Thomas C. Südhof

Keyword(s):

Synapse Formation ◽

Camp Signaling ◽

Protein Kinase Activity ◽

Physiological Mechanisms ◽

Ca1 Neurons ◽

Synaptic Targeting ◽

Dependent Protein ◽

Virus Tracing ◽

Camp Levels

The physiological mechanisms driving synapse formation are elusive. Although numerous signals are known to regulate synapses, it remains unclear which signaling mechanisms organize initial synapse assembly. Here, we describe new tools, referred to as “SynTAMs” for synaptic targeting molecules, that enable localized perturbations of cAMP signaling in developing postsynaptic specializations. We show that locally restricted suppression of postsynaptic cAMP levels or of cAMP-dependent protein-kinase activity severely impairs excitatory synapse formation without affecting neuronal maturation, dendritic arborization, or inhibitory synapse formation. In vivo, suppression of postsynaptic cAMP signaling in CA1 neurons prevented formation of both Schaffer-collateral and entorhinal-CA1/temporoammonic-path synapses, suggesting a general principle. Retrograde trans-synaptic rabies virus tracing revealed that postsynaptic cAMP signaling is required for continuous replacement of synapses throughout life. Given that postsynaptic latrophilin adhesion-GPCRs drive synapse formation and produce cAMP, we suggest that spatially restricted postsynaptic cAMP signals organize assembly of postsynaptic specializations during synapse formation.

Download Full-text

Spine growth precedes synapse formation in the adult neocortex in vivo

Nature Neuroscience ◽

10.1038/nn1747 ◽

2006 ◽

Vol 9 (9) ◽

pp. 1117-1124 ◽

Cited By ~ 341

Author(s):

Graham W Knott ◽

Anthony Holtmaat ◽

Linda Wilbrecht ◽

Egbert Welker ◽

Karel Svoboda

Keyword(s):

Synapse Formation

Download Full-text

Guidance of optic axons in vivo by a preformed adhesive pathway on neuroepithelial endfeet

Developmental Biology ◽

10.1016/0012-1606(84)90248-3 ◽

1984 ◽

Vol 106 (2) ◽

pp. 485-499 ◽

Cited By ~ 275

Author(s):

Jerry Silver ◽

Urs Rutishauser

Keyword(s):

Optic Axons

Download Full-text

Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo

Blood ◽

10.1182/blood-2002-04-1044 ◽

2002 ◽

Vol 100 (8) ◽

pp. 2908-2916 ◽

Cited By ~ 135

Author(s):

Teunis B. H. Geijtenbeek ◽

Peter C. Groot ◽

Martijn A. Nolte ◽

Sandra J. van Vliet ◽

Shanti T. Gangaram-Panday ◽

...

Keyword(s):

Marginal Zone ◽

Synapse Formation ◽

Intercellular Adhesion Molecule ◽

Pathogen Recognition ◽

Liver Sinusoidal Endothelial Cells ◽

Specific Polysaccharide ◽

Murine Homologue ◽

Encapsulated Bacteria ◽

Marginal Zone Macrophages

Antigen-presenting cells are localized in essentially every tissue, where they operate at the interface of innate and acquired immunity by capturing pathogens and presenting pathogen-derived peptides to T cells. C-type lectins are important pathogen recognition receptors and the C-type lectin, dendritic cell–specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), is unique in that, in addition to pathogen capture, it regulates adhesion processes such as DC trafficking and T-cell synapse formation. We have isolated a murine homologue of DC-SIGN that is identical to the previously reported murine homologue mSIGNR1. mSIGNR1 is more closely related to the human DC-SIGN homologue L-SIGN than to DC-SIGN itself because mSIGNR1 is specifically expressed by liver sinusoidal endothelial cells, similar to L-SIGN, and not by DCs. Moreover, mSIGNR1 is also expressed by medullary and subcapsular macrophages in lymph nodes and by marginal zone macrophages (MZMs) in the spleen. Strikingly, these MZMs are in direct contact with the bloodstream and efficiently capture specific polysaccharide antigens present on the surface of encapsulated bacteria. We have investigated the in vivo function of mSIGNR1 on MZMs in spleen. We demonstrate here that mSIGNR1 functions in vivo as a pathogen recognition receptor on MZMs that capture blood-borne antigens, which are rapidly internalized and targeted to lysosomes for processing. Moreover, the antigen capture is completely blocked in vivo by the blocking mSIGNR1-specific antibodies. Thus, mSIGNR1, a murine homologue of DC-SIGN, is important in the defense against pathogens and this study will facilitate further investigations into the in vivo function of DC-SIGN and its homologues.

Download Full-text