scholarly journals cAMP controls a trafficking mechanism that directs the neuron specificity and subcellular placement of electrical synapses

2021 ◽  
Author(s):  
Sierra Palumbos ◽  
Rachel Skelton ◽  
Rebecca McWhirter ◽  
Amanda Mitchell ◽  
Isaiah Swann ◽  
...  
Keyword(s):  
Nervous System ◽  
Gap Junction ◽  
Motor Neurons ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Electrical Synapse ◽  
Transcriptional Program ◽  
Electrical Synapses ◽  
C Elegans

Electrical synapses are established between specific neurons and within distinct subcellular compartments, but the mechanisms that direct gap junction assembly in the nervous system are largely unknown. Here we show that a transcriptional program tunes cAMP signaling to direct the neuron-specific assembly and placement of electrical synapses in the C. elegans motor circuit. For these studies, we use live cell imaging to visualize electrical synapses in vivo and a novel optogenetic assay to confirm that they are functional. In VA motor neurons, the UNC-4 transcription factor blocks expression of cAMP antagonists that promote gap junction miswiring. In unc-4 mutants, VA electrical synapses are established with an alternative synaptic partner and are repositioned from the VA axon to soma. We show that cAMP counters these effects by driving gap junction trafficking into the VA axon for electrical synapse assembly. Thus, our experiments in an intact nervous system establish that cAMP regulates gap junction trafficking for the biogenesis of electrical synapses.

scholarly journals C. elegans neurons have functional dendritic spines

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Andrea Cuentas-Condori ◽  
Ben Mulcahy ◽  
Siwei He ◽  
Sierra Palumbos ◽  
Mei Zhen ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Dendritic Spines ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Super Resolution ◽  
Live Cell ◽  
Model Organisms ◽  
Spine Density ◽  
C Elegans ◽  
Spine Function

Dendritic spines are specialized postsynaptic structures that transduce presynaptic signals, are regulated by neural activity and correlated with learning and memory. Most studies of spine function have focused on the mammalian nervous system. However, spine-like protrusions have been reported in C. elegans (Philbrook et al., 2018), suggesting that the experimental advantages of smaller model organisms could be exploited to study the biology of dendritic spines. Here, we used super-resolution microscopy, electron microscopy, live-cell imaging and genetics to show that C. elegans motor neurons have functional dendritic spines that: (1) are structurally defined by a dynamic actin cytoskeleton; (2) appose presynaptic dense projections; (3) localize ER and ribosomes; (4) display calcium transients triggered by presynaptic activity and propagated by internal Ca++ stores; (5) respond to activity-dependent signals that regulate spine density. These studies provide a solid foundation for a new experimental paradigm that exploits the power of C. elegans genetics and live-cell imaging for fundamental studies of dendritic spine morphogenesis and function.

scholarly journals Asymmetry of an intracellular scaffold at vertebrate electrical synapses

2017 ◽  
Author(s):  
Audrey J Marsh ◽  
Jennifer Carlisle Michel ◽  
Anisha P Adke ◽  
Emily L Heckman ◽  
Adam C Miller
Keyword(s):  
Gap Junction ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Electrical Synapse ◽  
Electrical Synapses ◽  
Gap Junction Channels ◽  
Junction Protein ◽  
Chemical Synapses ◽  
And Function

AbstractNeuronal synaptic connections are electrical or chemical and together are essential to dynamically defining neural circuit function. While chemical synapses are well known for their biochemical complexity, electrical synapses are often viewed as comprised solely of neuronal gap junction channels that allow direct ionic and metabolic communication. However, associated with the gap junction channels are structures observed by electron microscopy called the Electrical Synapse Density (ESD). The ESD has been suggested to be critical for the formation and function of the electrical synapse, yet the biochemical makeup of these structures is poorly understood. Here we find that electrical synapse formation in vivo requires an intracellular scaffold called Tight Junction Protein 1b (Tjp1b). Tjp1b is localized to electrical synapses where it is required for the stabilization of the gap junction channels and for electrical synapse function. Strikingly, we find that Tjp1b protein localizes and functions asymmetrically, exclusively on the postsynaptic side of the synapse. Our findings support a novel model in which there is molecular asymmetry at the level of the intracellular scaffold that is required for building the electrical synapse. ESD molecular asymmetries may be a fundamental motif of all nervous systems and could support functional asymmetry at the electrical synapse.

scholarly journals Dendritic spines on GABAergic neurons respond to cholinergic signaling in theCaenorhabditis elegansmotor circuit

2019 ◽  
Author(s):  
Andrea Cuentas-Condori ◽  
Ben Mulcahy ◽  
Siwei He ◽  
Sierra Palumbos ◽  
Mei Zhen ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Motor Neurons ◽  
Dendritic Spines ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Spine Density ◽  
C Elegans ◽  
Cholinergic Signaling ◽  
Spine Morphogenesis

SUMMARYDendritic spines are specialized postsynaptic structures that detect and integrate presynaptic signals. The shape and number of dendritic spines are regulated by neural activity and correlated with learning and memory. Most studies of spine function have focused on the mammalian nervous system. However, spine-like protrusions have been previously reported in invertebrates, suggesting that the experimental advantages of smaller model organisms could be exploited to study the biology of dendritic spines. Here, we document the presence of dendritic spines inCaenorhabditis elegansmotor neurons. We used super-resolution microscopy, electron microscopy, live-cell imaging and genetic manipulation to show that GABAergic motor neurons display functional dendritic spines. Our analysis revealed salient features of dendritic spines: (1) A key role for the actin cytoskeleton in spine morphogenesis; (2) Postsynaptic receptor complexes at the tips of spines in close proximity to presynaptic active zones; (3) Localized postsynaptic calcium transients evoked by presynaptic activity; (4) The presence of endoplasmic reticulum and ribosomes; (5) The regulation of spine density by presynaptic activity. These studies provide a solid foundation for a new experimental paradigm that exploits the power ofC. elegansgenetics and live-cell imaging for fundamental studies of dendritic spine morphogenesis and function.HIGHLIGHTS-Spines inC. elegansGABAergic motor neurons are enriched in actin cytoskeleton.-Spines are dynamic structures.-Spines display Ca++transients coupled with presynaptic activation.-Spine density is regulated during development and is modulated by actin dynamics and cholinergic signaling.

A quinoline-based probe for effective and selective sensing of aspartic acid in aqueous medium: in vitro and in vivo live cell imaging

2019 ◽  
Vol 6 (11) ◽  
pp. 3237-3244 ◽  
Author(s):  
C. Elamathi ◽  
R. J. Butcher ◽  
A. Mohankumar ◽  
P. Sundararaj ◽  
A. Madankumar ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Aspartic Acid ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
C Elegans ◽  
Highly Sensitive ◽  
Mcf 7

A highly sensitive and selective “on–off–on” chemosensor for aspartic acid in aqueous solution was established. In vitro live cell imaging against MCF 7 cells and in vivo imaging using C. elegans were successfully demonstrated.

scholarly journals Visualizing the metazoan proliferation-quiescence decision in vivo

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Rebecca C Adikes ◽  
Abraham Q Kohrman ◽  
Michael A Q Martinez ◽  
Nicholas J Palmisano ◽  
Jayson J Smith ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Cell Cycle Control ◽  
Cell Lineage ◽  
Live Cell ◽  
C Elegans ◽  
Imaging Tool ◽  
Wide Range

Cell proliferation and quiescence are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these key events of the cell cycle in C. elegans and zebrafish through live-cell imaging. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from quiescent cells in G0, revealing a possible commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. Finally, we derive a predictive model of future proliferation behavior in C. elegans based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell cycle control in a wide-range of developmental contexts.

scholarly journals Plasticity of the electrical connectome of C. elegans

2018 ◽  
Author(s):  
Abhishek Bhattacharya ◽  
Ulkar Aghayeva ◽  
Emily Berghoff ◽  
Oliver Hobert
Keyword(s):  
Nervous System ◽  
Expression Patterns ◽  
Electrical Synapse ◽  
Neuron Type ◽  
Electrical Synapses ◽  
C Elegans ◽  
Regulatory Strategies ◽  
A Genome ◽  
Specific Manner ◽  
Foxo Transcription Factors

AbstractThe patterns of electrical synapses of an animal nervous system (“electrical connectome”), as well as the functional properties and plasticity of electrical synapses, are defined by the neuron type-specific complement of electrical synapse constituents. We systematically examine here properties of the electrical connectome of the nematode C. elegans through a genome- and nervous system-wide analysis of the expression pattern of the central components of invertebrate electrical synapses, the innexins, revealing highly complex combinatorial patterns of innexin expression throughout the nervous system. We find that the complex expression patterns of 12 out of 14 neuronally expressed innexins change in a strikingly neuron type-specific manner throughout most of the nervous system, if animals encounter harsh environmental conditions and enter the dauer arrest stage. We systematically describe the plasticity of locomotory patterns of dauer stage animals and, by analyzing several individual electrical synapses, we demonstrate that dauer stage-specific electrical synapse remodeling is responsible for specific aspects of the altered locomotory patterns as well as altered chemosensory behavior of dauer stage animals. We describe an intersectional gene regulatory mechanism, involving terminal selector and FoxO transcription factors that are responsible for inducing innexin expression changes in a neuron type- and environment-specific manner. Taken together, our studies illustrate the remarkably dynamic nature of electrical synapses on a nervous system-wide level and describe regulatory strategies for how these alterations are achieved.

scholarly journals A Decade of Imaging Cellular Motility and Interaction Dynamics in the Immune System

Science ◽  
2012 ◽  
Vol 336 (6089) ◽  
pp. 1676-1681 ◽  
Author(s):  
Ronald N. Germain ◽  
Ellen A. Robey ◽  
Michael D. Cahalan
Keyword(s):  
Lymph Nodes ◽  
Live Cell Imaging ◽  
Quantitative Measurement ◽  
Cell Imaging ◽  
Plasma Cells ◽  
Effector T Cells ◽  
Cellular Interactions ◽  
Cellular Motility ◽  
Response Dynamics

To mount an immune response, lymphocytes must recirculate between the blood and lymph nodes, recognize antigens upon contact with specialized presenting cells, proliferate to expand a small number of clonally relevant lymphocytes, differentiate to antibody-producing plasma cells or effector T cells, exit from lymph nodes, migrate to tissues, and engage in host-protective activities. All of these processes involve motility and cellular interactions—events that were hidden from view until recently. Introduced to immunology by three papers in this journal in 2002, in vivo live-cell imaging studies are revealing the behavior of cells mediating adaptive and innate immunity in diverse tissue environments, providing quantitative measurement of cellular motility, interactions, and response dynamics. Here, we review themes emerging from such studies and speculate on the future of immunoimaging.

Sign in / Sign up

Export Citation Format

Share Document