scholarly journals Imaging sensory transmission and neuronal plasticity in primary sensory neurons with a positively tuned voltage indicator

2021 ◽  
Author(s):  
Yu Shin Kim ◽  
Yan Zhang ◽  
John Shannonhouse ◽  
Ruben Gomez ◽  
Hyeonwi Son ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Dynamic Range ◽  
Temporal Dynamics ◽  
Tissue Injury ◽  
Spatiotemporal Analysis ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Integration Mechanisms ◽  
External Stimuli

Abstract Detection of somatosensory inputs requires conversion of external stimuli into electrical signals by activation of primary sensory neurons. The mechanisms by which heterogeneous primary sensory neurons encode different somatosensory inputs remains unclear. In vivo dorsal root ganglia (DRG) imaging using genetically-encoded Ca2+ indicators (GECIs) is currently the best technique for this purpose mapping neuronal function in DRG circuits by providing an unprecedented spatial and populational resolution. It permits the simultaneous imaging of >1800 neurons/DRG in live mice. However, this approach is not ideal given that Ca2+ is a second messenger and has inherently slow response kinetics. In contrast, genetically-encoded voltage indicators (GEVIs) have the potential to track voltage changes in multiple neurons in real time but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4.4-Kv, a novel positively tuned GEVI, to dissect the temporal dynamics of noxious and non-noxious neuronal signals during mechanical, thermal, or chemical stimulation in DRG neurons of live mice. ASAP4.4-Kv is sufficiently bright and fast enough to optically characterize individual neuron coding dynamics. Notably, using ASAP4.4-Kv, we uncovered cell-to-cell electrical synchronization between adjacent DRG neurons and robust dynamic transformations in sensory coding following tissue injury. Finally, we found that a combination of GEVI and GECI imaging empowered in vivo optical studies of sensory signal processing and integration mechanisms with optimal spatiotemporal analysis.

scholarly journals Imaging sensory transmission and neuronal plasticity in primary sensory neurons with genetically-encoded voltage indicators

2021 ◽  
Author(s):  
Yan Zhang ◽  
John Shannonhouse ◽  
Ruben Gomez ◽  
Hyeonwi Son ◽  
Hirotake Ishida ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Dynamic Range ◽  
Temporal Dynamics ◽  
Tissue Injury ◽  
Spatiotemporal Analysis ◽  
Primary Sensory Neurons ◽  
Simultaneous Imaging ◽  
Integration Mechanisms ◽  
External Stimuli

Detection of somatosensory inputs requires conversion of external stimuli into electrical signals by activation of primary sensory neurons. The mechanisms by which heterogeneous primary sensory neurons encode different somatosensory inputs remains unclear. In vivo dorsal root ganglia (DRG) imaging using genetically-encoded Ca2+ indicators (GECIs) is currently the best technique for this purpose by providing an unprecedented spatial and populational resolution. It permits the simultaneous imaging of >1800 neurons/DRG in live mice. However, this approach is not ideal given that Ca2+ is a second messenger and has inherently slow response kinetics. In contrast, genetically-encoded voltage indicators (GEVIs) have the potential to track voltage changes in multiple neurons in real time but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4, a novel GEVI, to dissect the temporal dynamics of noxious and non-noxious neuronal signals during mechanical, thermal, or chemical stimulation in DRG of live mice. ASAP4 is sufficiently bright and fast enough to optically characterize individual neuron coding dynamics. Notably, using ASAP4, we uncovered cell-to-cell electrical synchronization between adjacent DRG neurons and robust dynamic transformations in sensory coding following tissue injury. Finally, we found that a combination of GEVI and GECI imaging empowered in vivo optical studies of sensory signal processing and integration mechanisms with optimal spatiotemporal analysis.

Vasoinhibin Suppresses the Neurotrophic Effects of VEGF and NGF in Newborn Rat Primary Sensory Neurons

2017 ◽  
Vol 106 (3) ◽  
pp. 221-233 ◽  
Author(s):  
Ximena Castillo ◽  
Zesergio Melo ◽  
Alfredo Varela-Echavarría ◽  
Elisa Tamariz ◽  
Rodrigo M. Aroña ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neurite Outgrowth ◽  
Sensory Neurons ◽  
Target Cells ◽  
Vascular Endothelial ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Newborn Rat ◽  
Akt Phosphorylation ◽  
Endothelial Growth Factor

Background/Aims: Studies on the biological actions of vasoinhibins have focused mainly on endothelial cells. However, there is incipient knowledge about how vasoinhibins affect the nervous system, even if the target cells and mechanisms of action involved in these effects are unknown. Methods: In order to determine if neurons are direct targets of vasoinhibins, we examined cellular outcomes and the intracellular pathways involved in the neuronal actions of vasoinhibins using newborn rat dorsal root ganglion (DRG) neurons as a model system. Results: Vascular endothelial growth factor (VEGF) or nerve growth factor (NGF) treatment for 48 h resulted in neurite outgrowth stimulation in both DRG cultured explants and isolated primary sensory neurons. Interestingly, a recombinant vasoinhibin containing the first 123 amino acids of human prolactin antagonized the VEGF- and NGF-induced stimulation of neurite outgrowth. Vasoinhibin significantly reduced the density of neurites in DRG explants and obliterated neuritogenesis in isolated DRG neurons in primary culture, supporting a direct neuronal effect of vasoinhibin. In cultures of isolated DRG cells, virtually all β3-tubulin-labeled cells express TrkA, and the majority of these cells also express VEGFR2. Short-term VEGF or NGF treatment of DRG explants resulted in increased ERK1/2 and AKT phosphorylation, whereas incubation of DRG with the combination of either VEGF or NGF together with vasoinhibin resulted in blunted VEGF- or NGF-induced phosphorylation of both ERK1/2 and AKT. Conclusion: Our results show that primary sensory neurons are direct targets of vasoinhibin, and suggest that vasoinhibin inhibition of neurite outgrowth involves the disruption of ERK and AKT phosphorylation cascades.

scholarly journals Upregulation of class I major histocompatibility complex gene expression in primary sensory neurons, satellite cells, and Schwann cells of mice in response to acute but not latent herpes simplex virus infection in vivo.

1994 ◽  
Vol 180 (3) ◽  
pp. 841-850 ◽  
Author(s):  
R A Pereira ◽  
D C Tscharke ◽  
A Simmons
Keyword(s):  
Gene Expression ◽  
Major Histocompatibility Complex ◽  
Schwann Cells ◽  
Sensory Neurons ◽  
Neural Tissue ◽  
Class I ◽  
Primary Sensory Neurons ◽  
Histocompatibility Complex ◽  
Simplex Virus

Major histocompatibility complex (MHC) deficiency is typical of almost all resident cells in normal neural tissue. However, CD8+ T cells, which recognize antigenic peptides in the context of class I MHC molecules, are known to mediate clearance of herpes simplex virus (HSV) from spinal ganglia of experimentally infected mice, leading to the hypothesis that class I expression in the peripheral nervous system must be upregulated in response to HSV infection. In addressing this hypothesis it is shown, in BALB/c (H-2d) mice, that normally deficient class I transcripts transiently accumulate in peripheral nerve Schwann cells, ganglionic satellite cells, and primary sensory neurons, indicating that in each of these cell types class I expression is regulated at the transcriptional level in vivo. Furthermore, for 3-4 wk after infection, H-2Kd/Dd antigens are expressed by satellite and Schwann cells but not neurons, suggesting additional posttranscriptional regulation of class I synthesis in neurons. Alternatively, the class I RNAs induced in neurons may not be derived from classical class I genes. Factors regulating H-2 class I expression emanate from within infected ganglia, probably from infected neurons themselves. However, induction of class I molecules was not maintained during latency, when viral gene expression in neurons is restricted to a single region within the virus repeats. These data have implications for the long-term survival of cells in HSV-infected neural tissue.

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