scholarly journals Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Tong Wang ◽  
Sally Martin ◽  
Tam H. Nguyen ◽  
Callista B. Harper ◽  
Rachel S. Gormal ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Hippocampal Neurons ◽  
Super Resolution ◽  
Retrograde Transport ◽  
Synaptic Activity ◽  
Neurotrophin Receptor ◽  
Independent Manner ◽  
Cholera Toxin Subunit B ◽  
Super Resolution Microscopy ◽  
Subunit B

AbstractAxonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic activity markedly increased the flux of plasma membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured in microfluidic devices, and liveDrosophilalarval motor neurons. Electron and super-resolution microscopy analyses revealed that the fast-moving sub-diffraction-limited CTB carriers contained the TrkB neurotrophin receptor, transiently activated by synaptic activity in a BDNF-independent manner. Pharmacological and genetic inhibition of TrkB activation selectively prevented the coupling between synaptic activity and the retrograde flux of signalling endosomes. TrkB activity therefore controls the encoding of synaptic activity experienced by nerve terminals, digitalized as the flux of retrogradely transported signalling endosomes.

scholarly journals Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75NTR

2002 ◽  
Vol 156 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Giovanna Lalli ◽  
Giampietro Schiavo
Keyword(s):  
Motor Neurons ◽  
Tetanus Toxin ◽  
Experimental System ◽  
Retrograde Transport ◽  
Endocytic Pathway ◽  
Neurotrophin Receptor ◽  
Tubular Structures ◽  
Growth And Survival ◽  
Membrane Compartments ◽  
The Central Nervous System

Axonal retrograde transport is essential for neuronal growth and survival. However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized. To shed light on this pathway, we established an experimental system for the visualization and the quantitative study of retrograde transport in living motor neurons based on a fluorescent fragment of tetanus toxin (TeNT HC). Morphological and kinetic analysis of TeNT HC retrograde carriers reveals two major groups of organelles: round vesicles and fast tubular structures. TeNT HC carriers lack markers of the classical endocytic pathway and are not acidified during axonal transport. Importantly, TeNT HC and NGF share the same retrograde transport organelles, which are characterized by the presence of the neurotrophin receptor p75NTR. Our results provide the first direct visualization of retrograde transport in living motor neurons, and reveal a novel retrograde route that could be used both by physiological ligands (i.e., neurotrophins) and TeNT to enter the central nervous system.

scholarly journals The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ana Rita Costa ◽  
Sara C Sousa ◽  
Rita Pinto-Costa ◽  
José C Mateus ◽  
Cátia DF Lopes ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Myosin Ii ◽  
Super Resolution ◽  
Loss Of Function ◽  
Axon Diameter ◽  
Heavy Chains ◽  
Axonal Diameter ◽  
Muscle Myosin ◽  
Super Resolution Microscopy ◽  
Actin Rings

Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.

scholarly journals Specificity of Sensory and Motor Neurons Associated with BL40 and GB30 in the Rat: A Dual Fluorescent Labeling Study

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Jingjing Cui ◽  
Lijuan Ha ◽  
Xinlong Zhu ◽  
Fuchun Wang ◽  
Xianghong Jing ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Laser Scanning ◽  
Ventral Horn ◽  
Fluorescent Labeling ◽  
Laser Scanning Confocal Microscope ◽  
Alexa Fluor ◽  
Neural Tracing ◽  
Cholera Toxin Subunit B ◽  
Spinal Segments ◽  
Subunit B

The purpose of this study is to investigate the specific innervations on “Weizhong” (BL40) and “Huantiao” (GB30) by using a dual neural tracing technique. After Alexa Fluor 488 and 594 conjugates of cholera toxin subunit B (AF488/594-CTB) were, respectively, injected into BL40 and GB30 in the same rat, the labeled sensory and motor neurons were examined in the rat’s dorsal root ganglia (DRGs) and spinal cord at thoracic (T) and lumbar (L) segments with a laser scanning confocal microscope. In the cases of BL40 injection, AF488-CTB labeled sensory and motor neurons were located in L2–6DRGs and on the mediolateral part of spinal ventral horn from L3to L5segments, respectively. By contrast, in the cases of GB30 injection, AF594-CTB labeled sensory and motor neurons were distributed in T13-L6DRGs and on the anterolateral part of spinal ventral horn from L1to L5segments, respectively. These results indicate that the sensory and motor neurons associated with BL40 and GB30 are located in different spinal segments and regions in the nervous system, providing the neuroanatomical evidence to serve the specificity of acupoints.

scholarly journals Aberrant Morphology and Residual Transmitter Release at the Munc13-Deficient Mouse Neuromuscular Synapse

2005 ◽  
Vol 25 (14) ◽  
pp. 5973-5984 ◽  
Author(s):  
Frédérique Varoqueaux ◽  
Michèle S. Sons ◽  
Jaap J. Plomp ◽  
Nils Brose
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Vesicle ◽  
Motor Neurons ◽  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Neuromuscular Junctions ◽  
Neuromuscular Synapse ◽  
Synaptic Activity ◽  
Neuromuscular Synaptogenesis ◽  
Deficient Mice

ABSTRACT In cultured hippocampal neurons, synaptogenesis is largely independent of synaptic transmission, while several accounts in the literature indicate that synaptogenesis at cholinergic neuromuscular junctions in mammals appears to partially depend on synaptic activity. To systematically examine the role of synaptic activity in synaptogenesis at the neuromuscular junction, we investigated neuromuscular synaptogenesis and neurotransmitter release of mice lacking all synaptic vesicle priming proteins of the Munc13 family. Munc13-deficient mice are completely paralyzed at birth and die immediately, but form specialized neuromuscular endplates that display typical synaptic features. However, the distribution, number, size, and shape of these synapses, as well as the number of motor neurons they originate from and the maturation state of muscle cells, are profoundly altered. Surprisingly, Munc13-deficient synapses exhibit significantly increased spontaneous quantal acetylcholine release, although fewer fusion-competent synaptic vesicles are present and nerve stimulation-evoked secretion is hardly elicitable and strongly reduced in magnitude. We conclude that the residual transmitter release in Munc13-deficient mice is not sufficient to sustain normal synaptogenesis at the neuromuscular junction, essentially causing morphological aberrations that are also seen upon total blockade of neuromuscular transmission in other genetic models. Our data confirm the importance of Munc13 proteins in synaptic vesicle priming at the neuromuscular junction but indicate also that priming at this synapse may differ from priming at glutamatergic and γ-aminobutyric acid-ergic synapses and is partly Munc13 independent. Thus, non-Munc13 priming proteins exist at this synapse or vesicle priming occurs in part spontaneously: i.e., without dedicated priming proteins in the release machinery.

Neuroanatomical Basis for Acupuncture Point Pc8 in the Rat: Neural Tracing Study with Cholera Toxin Subunit B

2013 ◽  
Vol 31 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Jing-Jing Cui ◽  
Li-Juan Ha ◽  
Xin-Long Zhu ◽  
Hong Shi ◽  
Fu-Chun Wang ◽  
...  
Keyword(s):  
Cholera Toxin ◽  
Dorsal Horn ◽  
Motor Neurons ◽  
Spinal Dorsal Horn ◽  
Acupuncture Point ◽  
Cuneate Nucleus ◽  
Spinal Dorsal ◽  
Neural Tracing ◽  
Cholera Toxin Subunit B ◽  
Subunit B

Objectives This study was performed to investigate the innervations related to acupuncture point PC8 in rats using a neural tracing technique. Methods After 6 μL of 1% cholera toxin subunit B (CTB) was injected into the site between the second and third metacarpal bone in rats, a corresponding site to acupuncture point PC8 in the human body, CTB labelling was examined with immunofluorescence and immunohistochemistry in the dorsal root ganglia (DRG), spinal cord and brainstem. Results All CTB labelling appeared on the ipsilateral side of the injection. The labelled sensory neurons distributed from cervical (C)6 to thoracic (T)1 DRG, while the labelled motor neurons were located on the dorsolateral part of the spinal ventral horn ranging from the C6 to T1 segments. In addition, the transganglionically-labelled axonal terminals were found to be dense in the medial part of laminae 3–4 from C6 to the T1 spinal dorsal horn, as far as in the cuneate nucleus. Conclusions These results indicate that sensory and motor neurons associated with PC8 distribute in a distinct segmental pattern. The sensory information from PC8 could be transganglionically transported to the spinal dorsal horn and cuneate nucleus.

scholarly journals Super-Resolution Microscopy Reveals Presynaptic Localization of the ALS/FTD Related Protein FUS in Hippocampal Neurons

2016 ◽  
Vol 9 ◽  
Author(s):  
Michael Schoen ◽  
Jochen M. Reichel ◽  
Maria Demestre ◽  
Stefan Putz ◽  
Dhruva Deshpande ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Super Resolution ◽  
Related Protein ◽  
Super Resolution Microscopy

CAP1 and cofilin1 cooperate in neuronal actin dynamics, growth cone function and neuron connectivity

2020 ◽  
Author(s):  
Felix Schneider ◽  
Thuy-An Duong ◽  
Isabell Metz ◽  
Jannik Winkelmeier ◽  
Christian A. Hübner ◽  
...  
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Super Resolution ◽  
Growth Cones ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Control Growth ◽  
Cone Function ◽  
And Function ◽  
Super Resolution Microscopy

AbstractNeuron connectivity depends on growth cones that navigate axons through the developing brain. Growth cones protrude and retract actin-rich structures to sense guidance cues. These cues control local actin dynamics and steer growth cones towards attractants and away from repellents, thereby directing axon outgrowth. Hence, actin binding proteins (ABPs) moved into the focus as critical regulators of neuron connectivity. We found cyclase-associated protein 1 (CAP1), an ABP with unknown brain function, abundant in growth cones. Super-resolution microscopy and live cell imaging combined with pharmacological approaches on hippocampal neurons from gene-targeted mice revealed a crucial role for CAP1 in actin dynamics that is critical for growth cone morphology and function. Growth cone defects in mutant neurons compromised neuron differentiation and was associated with impaired neuron connectivity in CAP1 mutant brains. Mechanistically, we found that CAP1 and cofilin1 synergistically control growth cone actin dynamic and morphology. Together, we identified CAP1 as a novel actin regulator in growth cone that is relevant for neuron connectivity.

Sign in / Sign up

Export Citation Format

Share Document