scholarly journals Focal Laser Stimulation of Fly Nociceptors Activates Distinct Axonal and Dendritic Ca2+ Signals

2021 ◽  
Author(s):  
Rajshekhar Basak ◽  
Sabyasachi Sutradhar ◽  
Jonathon Howard
Keyword(s):  
Morphological Changes ◽  
Mechanical Stimuli ◽  
Direct Stimulation ◽  
Calcium Signals ◽  
Precise Position ◽  
Contact Pathway ◽  
Contact Response ◽  
Escape Behaviors ◽  
Class Iv ◽  
Stimulation Of

Drosophila Class IV neurons are polymodal nociceptors that detect noxious mechanical, thermal, optical and chemical stimuli. Escape behaviors in response to attacks by parasitoid wasps are dependent on Class IV cells, whose highly branched dendritic arbors form a fine meshwork that is thought to enable detection of the wasp's needle-like ovipositor barb. To understand how mechanical stimuli trigger cellular responses, we used a focused 405-nm laser to create highly local lesions to probe the precise position needed in evoke responses. By imaging calcium signals in dendrites, axons, and soma in response to stimuli of varying positions, intensities and spatial profiles, we discovered that there are two distinct nociceptive pathways. Direct stimulation to dendrites (the contact pathway) produces calcium responses in axons, dendrites and the cell body whereas stimulation adjacent to the dendrite (the non-contact pathway) produces calcium responses in the axons only. We interpret the non-contact pathway as damage to adjacent cells releasing diffusible molecules that act on the dendrites. Axonal responses have higher sensitivities and shorter latencies. In contrast, dendritic responses have lower sensitivities and longer latencies. Stimulation of finer, distal dendrites leads to smaller responses than stimulation of coarser, proximal dendrites, as expected if the contact response depends on the geometric overlap of the laser profile and the dendrite diameter. Because the axon signals to the CNS to trigger escape behaviors, we propose that the density of the dendritic meshwork is high not only to enable direct contact with the ovipositor, but also to enable neuronal activation via diffusing signals from damaged surrounding cells. Dendritic contact evokes responses throughout the dendritic arbor, even to regions distant and distal from the stimulus. These dendrite-wide calcium signals may facilitate hyperalgesia or cellular morphological changes following dendritic damage.

Reflex Responses in Human Jaw, Lip, and Tongue Muscles Elicited by Mechanical Stimulation

1987 ◽  
Vol 30 (1) ◽  
pp. 70-79 ◽  
Author(s):  
Christine M. Weber ◽  
Anne Smith
Keyword(s):  
Mechanical Stimuli ◽  
Observable Effect ◽  
Direct Stimulation ◽  
Muscle Spindle Afferents ◽  
Lower Lip ◽  
Reflex Responses ◽  
Reflex Pathways ◽  
Tongue Muscles ◽  
Jaw Muscle ◽  
Stimulation Of

Reflex responses in human jaw, lip, and tongue muscles were elicited with brief, innocuous mechanical stimuli. Stimuli were applied to the masseter (and overlying tissue), the lower lip vermilion, and the tongue dorsum. Reflex responses occurred in masseter, orbicularis oris inferior, and genioglossus muscles upon direct stimulation of the sites associated with each of these muscles. In contrast, reflex responses to stimulation of "distant" sites occurred almost exclusively in masseter; that is, stimulation of the lip and tongue produced responses in masseter, but, stimulation of jaw muscle spindle afferents and overlying cutaneous receptors had no observable effect on activity in genioglossus or orbicularis oris inferior muscles. It could be hypothesized that the motoneuron pools controlling jaw muscles are more sensitive to synaptic inputs generated by reflex pathways originating in other structures. The sensitivity of the masseter muscle to inputs from the lip and tongue may serve to link these structures functionally.

scholarly journals The Role of BMP Signaling in Osteoclast Regulation

2021 ◽  
Vol 9 (3) ◽  
pp. 24
Author(s):  
Brian Heubel ◽  
Anja Nohe
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Diseases ◽  
Bmp Signaling ◽  
Bone Homeostasis ◽  
Direct Stimulation ◽  
Federal Drug Administration ◽  
Bmp Pathway ◽  
Stimulation Of

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.

scholarly journals A Novel Bioreactor for the Mechanical Stimulation of Clinically Relevant Scaffolds for Muscle Tissue Engineering Purposes

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 474
Author(s):  
Silvia Todros ◽  
Silvia Spadoni ◽  
Edoardo Maghin ◽  
Martina Piccoli ◽  
Piero G. Pavan
Keyword(s):  
Mechanical Stimulation ◽  
Strain Range ◽  
Tensile Tests ◽  
Muscular Tissue ◽  
Fe Model ◽  
Mechanical Stimuli ◽  
Physiological Strain ◽  
Cellular Alignment ◽  
Stimulation Of

Muscular tissue regeneration may be enhanced in vitro by means of mechanical stimulation, inducing cellular alignment and the growth of functional fibers. In this work, a novel bioreactor is designed for the radial stimulation of porcine-derived diaphragmatic scaffolds aiming at the development of clinically relevant tissue patches. A Finite Element (FE) model of the bioreactor membrane is developed, considering two different methods for gripping muscular tissue patch during the stimulation, i.e., suturing and clamping with pliers. Tensile tests are carried out on fresh and decellularized samples of porcine diaphragmatic tissue, and a fiber-reinforced hyperelastic constitutive model is assumed to describe the mechanical behavior of tissue patches. Numerical analyses are carried out by applying pressure to the bioreactor membrane and evaluating tissue strain during the stimulation phase. The bioreactor designed in this work allows one to mechanically stimulate tissue patches in a radial direction by uniformly applying up to 30% strain. This can be achieved by adopting pliers for tissue clamping. Contrarily, the use of sutures is not advisable, since high strain levels are reached in suturing points, exceeding the physiological strain range and possibly leading to tissue laceration. FE analysis allows the optimization of the bioreactor configuration in order to ensure an efficient transduction of mechanical stimuli while preventing tissue damage.

scholarly journals Effects of innate immune receptor stimulation on extracellular α-synuclein uptake and degradation by brain resident cells

2021 ◽  
Author(s):  
Changyoun Kim ◽  
Somin Kwon ◽  
Michiyo Iba ◽  
Brian Spencer ◽  
Edward Rockenstein ◽  
...  
Keyword(s):  
Degradation Kinetics ◽  
Morphological Changes ◽  
Direct Interaction ◽  
Innate Immune ◽  
Pathological Feature ◽  
Tlr2 Expression ◽  
Immune Receptors ◽  
Age Related ◽  
Stimulation Of

AbstractSynucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in the spread of α-syn pathology, the detailed mechanism is still unknown. Neuroinflammation is another key pathological feature of synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). However, the species of α-syn aggregates varies from study to study, and how different α-syn aggregate species interact with innate immune receptors has yet to be addressed. Therefore, we investigated whether innate immune receptors can facilitate the uptake of different species of α-syn aggregates. Here, we examined whether stimulation of TLRs could modulate the cellular uptake and degradation of α-syn fibrils despite a lack of direct interaction. We observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes. Internalized α-syn was rapidly degraded in microglia regardless of whether TLR2 was stimulated. However, cellular α-syn uptake and degradation kinetics were not altered by TLR4 stimulation. In addition, upregulation of TLR2 expression in a synucleinopathy mouse model increased the density of Lewy-body-like inclusions and induced morphological changes in microglia. Together, these results suggest that cell type-specific modulation of TLR2 may be a multifaceted and promising therapeutic strategy for synucleinopathies; inhibition of neuronal and astroglial TLR2 decreases pathogenic α-syn transmission, but activation of microglial TLR2 enhances microglial extracellular α-syn clearance.

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

2012 ◽  
Vol 107 (10) ◽  
pp. 2742-2755 ◽  
Author(s):  
Max Eickenscheidt ◽  
Martin Jenkner ◽  
Roland Thewes ◽  
Peter Fromherz ◽  
Günther Zeck
Keyword(s):  
Electrical Stimulation ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Biophysical Model ◽  
Retinal Neurons ◽  
Direct Stimulation ◽  
Tungsten Electrode ◽  
Partial Restoration ◽  
Low Amplitude ◽  
Stimulation Of

Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array—insulated by an inert oxide—allows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.

53: Direct Stimulation of the Auditory Nerve: Feasibility of a Thin-Film Microelectrode Array

1996 ◽  
Vol 115 (2) ◽  
pp. P94-P95
Author(s):  
Derek A. Jones ◽  
H. Alexander Arts ◽  
Steven M. Bierer ◽  
David J Anderson
Keyword(s):  
Thin Film ◽  
Auditory Nerve ◽  
Microelectrode Array ◽  
Direct Stimulation ◽  
Stimulation Of

Transcorneal stimulation of trigeminal nerve afferents to increase cerebral blood flow in rats with cerebral vasospasm: a noninvasive method to activate the trigeminovascular reflex

2002 ◽  
Vol 97 (5) ◽  
pp. 1179-1183 ◽  
Author(s):  
Basar Atalay ◽  
Hayrunnisa Bolay ◽  
Turgay Dalkara ◽  
Figen Soylemezoglu ◽  
Kamil Oge ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Vasospasm ◽  
Trigeminal Nerve ◽  
Nerve Endings ◽  
Noninvasive Method ◽  
Direct Stimulation ◽  
Content Type ◽  
Fine Print ◽  
Stimulation Of

Object. The goal of this study was to investigate whether stimulation of trigeminal afferents in the cornea could enhance cerebral blood flow (CBF) in rats after they have been subjected to experimental subarachnoid hemorrhage (SAH). Cerebral vasospasm following SAH may compromise CBF and increase the risks of morbidity and mortality. Currently, there is no effective treatment for SAH-induced vasospasm. Direct stimulation of the trigeminal nerve has been shown to dilate constricted cerebral arteries after SAH; however, a noninvasive method to activate this nerve would be preferable for human applications. The authors hypothesized that stimulation of free nerve endings of trigeminal sensory fibers in the face might be as effective as direct stimulation of the trigeminal nerve. Methods. Autologous blood obtained from the tail artery was injected into the cisterna magna of 10 rats. Forty-eight and 96 hours later (five rats each) trigeminal afferents were stimulated selectively by applying transcorneal biphasic pulses (1 msec, 3 mA, and 30 Hz), and CBF enhancements were detected using laser Doppler flowmetry in the territory of the middle cerebral artery. Stimulation-induced changes in cerebrovascular parameters were compared with similar parameters in sham-operated controls (six rats). Development of vasospasm was histologically verified in every rat with SAH. Corneal stimulation caused an increase in CBF and blood pressure and a net decrease in cerebrovascular resistance. There were no significant differences between groups for these changes. Conclusions. Data from the present study demonstrate that transcorneal stimulation of trigeminal nerve endings induces vasodilation and a robust increase in CBF. The vasodilatory response of cerebral vessels to trigeminal activation is retained after SAH-induced vasospasm.

scholarly journals High frequency of cross-reactive cytotoxic T lymphocytes elicited during the virus-induced polyclonal cytotoxic T lymphocyte response.

1993 ◽  
Vol 177 (2) ◽  
pp. 317-327 ◽  
Author(s):  
S R Nahill ◽  
R M Welsh
Keyword(s):  
T Lymphocytes ◽  
Virus Infection ◽  
Cytotoxic T Lymphocytes ◽  
High Frequency ◽  
Class Ii ◽  
Class I ◽  
Direct Stimulation ◽  
Ctl Response ◽  
Cd4 Cell ◽  
Stimulation Of

Polyclonal stimulation of CD8+ cytotoxic T lymphocytes (CTL) occurs during infection with many viruses including those not known to transform CTL or encode superantigens. This polyclonal CTL response includes the generation of high levels of allospecific CTL directed against many class I haplotypes. In this report we investigated whether the allospecific CTL generated during an acute lymphocytic choriomeningitis virus (LCMV) infection of C57BL/6 mice were stimulated specifically by antigen recognition or nonspecifically by polyclonal mechanisms possibly involving lymphokines or superantigens. An examination of the ability of different strains of mice to induce high levels of CTL specific for a given alloantigen showed that most, but not all, strains generated high levels of allospecific CTL, and that their abilities to generate them mapped genetically to the major histocompatibility complex locus, exclusive of the class II region. This indicated that the virus-induced allospecific CTL generation was independent of the class II allotype, and mice depleted of CD4+ cells generated allospecific CTL, indicating independence of class II-CD4+ cell interactions and resulting CD4+ cell-secreted lymphokines. FACS staining with a variety of V beta-binding antibodies did not show a superantigen-like depletion or enrichment of any tested V beta + subset during infection. Several experiments provided evidence in support of direct stimulation of CD8+ cells via the T cell receptor: (a) both virus- and allo-specific killing were enriched within a given V beta subpopulation; (b) relative CTL precursor frequencies against different class I alloantigens changed during the course of virus infection; (c) the relative levels of virus-induced, allospecific CTL-mediated lysis at day 8 after infection did not parallel the CTL precursor frequencies before infection; and (d) limiting dilution analyses of day 8 LCMV-infected spleen cells stimulated by virus-infected syngeneic peritoneal exudate cells (PEC) revealed not only the expected virus-specific CTL clones, but also a high frequency of clones that were cross-reactive with allogeneic and virus-infected syngeneic targets. In addition to the virus cross-reactive allospecific CTL clones, virus-infected PEC also stimulated the generation of some allospecific clones that did not lyse virus-infected fibroblasts. Surprisingly, LCMV-infected PEC were much more efficient at stimulating allospecific CTL clones from day 8 LCMV-infected splenocytes than were allogeneic stimulators. These results indicate that at least part of the polyclonal allospecific CTL response elicited by acute virus infection is a consequence of the selective expansion of many clones of allospecific CTL which cross-react with virus-infected cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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