Individual Nerve Fibers Research Articles

Bioelectronic Medicines-A Novel Approach of Therapeutics in Current Epoch.

Bioelectronic medicines aim to diagnose and treat a wide range of illnesses and ailments, including cancer, rheumatoid arthritis, inflammatory bowel disease, obesity, diabetes, asthma, paralysis, blindness, bleeding, ischemia, organ transplantation, cardiovascular disease, and neurodegenerative diseases. The focus of bioelectronic medicine is on electrical signaling of the nervous system. Understanding the nervous system's regulatory roles and developing technologies that record, activate, or inhibit neural signaling to influence particular biological pathways. Bioelectronic medicine is an emerging therapeutic option with the interconnection between molecular medicine, neuroscience, and bioengineering. The creation of nerve stimulating devices that communicate with both the central and peripheral nervous systems has the potential to completely transform how we treat disorders. Although early clinical applications have been largely effective across entire nerves, the ultimate goal is to create implantable, miniature closed-loop systems that can precisely identify and modulate individual nerve fibers to treat a wide range of disorders. The data bases such as PubMed, and Clinicaltrial.gov.in were searched for scientific research, review and clinical trials on bioelectronic medicine. The field of bioelectronic medicine is trending at present. In recent years, researchers have extended the field's applications, undertaken promising clinical trials, and begun delivering therapies to patients, thus creating the groundwork for significant future advancements. Countries and organizations must collaborate across industries and regions to establish an atmosphere and guidelines that foster the advancement of the field and the fulfillment of its prospective advantages.

Research on the Pathogenesis of Hemifacial Spasm through Electrophysiological Studies

The cause of hemifacial spasm (HFS) is commonly linked to vascular compression of the facial nerve at the root exit zone. Microvascular decompression has become the most effective treatment for HFS. However, despite numerous electrophysiological studies investigating factors such as ephaptic transmission, ectopic excitation between individual nerve fibers, and hyperexcitability of the facial motor nucleus, there is still debate about the exact pathogenesis of HFS. For over 40 years, researchers have been conducting electrophysiological studies in clinical settings to better understand the pathogenesis of HFS. These studies have employed techniques including the lateral spread response, blink reflex test, facial F-waves, and transcranial electrical stimulation. Although a peripheral nerve mechanism was historically considered most likely to be responsible for this condition, recent studies are increasingly pointing to a central mechanism as the primary culprit behind HFS. This article seeks to shed light on the pathogenesis of HFS by reviewing the key findings from electrophysiological studies carried out over the years.

(Pre)diabetes and a higher level of glycaemic measures are continuously associated with corneal neurodegeneration assessed by corneal confocal microscopy: the Maastricht Study

Aims/hypothesisTo assess the associations between glucose metabolism status and a range of continuous measures of glycaemia with corneal nerve fibre measures, as assessed using corneal confocal microscopy.MethodsWe used population-based observational cross-sectional data from the Maastricht Study of N=3471 participants (mean age 59.4 years, 48.4% men, 14.7% with prediabetes, 21.0% with type 2 diabetes) to study the associations, after adjustment for demographic, cardiovascular risk and lifestyle factors, between glucose metabolism status (prediabetes and type 2 diabetes vs normal glucose metabolism) plus measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA1c, skin autofluorescence [SAF] and duration of diabetes) and composite Z-scores of corneal nerve fibre measures or individual corneal nerve fibre measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length and fractal dimension). We used linear regression analysis, and, for glucose metabolism status, performed a linear trend analysis.ResultsAfter full adjustment, a more adverse glucose metabolism status was associated with a lower composite Z-score for corneal nerve fibre measures (β coefficients [95% CI], prediabetes vs normal glucose metabolism −0.08 [−0.17, 0.03], type 2 diabetes vs normal glucose metabolism −0.14 [−0.25, −0.04]; linear trend analysis showed a p value of 0.001), and higher levels of measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA1c, SAF and duration of diabetes) were all significantly associated with a lower composite Z-score for corneal nerve fibre measures (per SD: −0.09 [−0.13, −0.05], −0.07 [−0.11, −0.03], −0.08 [−0.11, −0.04], −0.05 [−0.08, −0.01], −0.09 [−0.17, −0.001], respectively). In general, directionally similar associations were observed for individual corneal nerve fibre measures.Conclusions/interpretationTo our knowledge, this is the first population-based study to show that a more adverse glucose metabolism status and higher levels of glycaemic measures were all linearly associated with corneal neurodegeneration after adjustment for an extensive set of potential confounders. Our results indicate that glycaemia-associated corneal neurodegeneration is a continuous process that starts before the onset of type 2 diabetes. Further research is needed to investigate whether early reduction of hyperglycaemia can prevent corneal neurodegeneration.Graphical

Электронно-микроскопическое исследование зрительного нерва с токсическим невритом в эксперименте

Рurpose. To identify ultrastructural changes of the optic nerve in the area of the trellis plate in rabbits after exposure to methyl alcohol. Material and methods. A model of experimental optic neuritis with the introduction of methyl alcohol into the retrobulbar space was reproduced on 8 rabbits. The animals were removed from the experiment on the 14th, 30th, 90th and 180th days after the administration of methanol. Pieces of the optic nerve (1–2 mm) were isolated from the enucleated eyeballs in the area of the lattice plate and examined using a transmission electron microscope. Results. On the 14th day after the administration of methanol, signs of pronounced cytoplasmic edema and destruction of intracellular organelles were detected in the ganglion neurons of the rabbit retina in the area of the lattice plate. In individual nerve fibers of the optic nerve, myelin sheaths were stratified and unfolded, axons swelled. Structural changes were detected in astrocytes, especially in the processes around blood vessels. Macrophages of nervous tissue — microgliocytes — became active. Morphological changes indicated a violation of microcirculation and permeability of the hematoneural barrier. The basal membranes around the walls of blood vessels were compacted. Intracellular organelles were destroyed in the cytoplasm of endothelial cells, hemostasis was determined inside the vessels. Subsequently, on the 30–90th day of the experiment, dystrophic and destructive changes in the cytoplasm of ganglion cells and their processes forming the optic nerve, as well as surrounding gliocytes progressed. There were signs of gliofibrosis. Destructive processes and gliofibrosis of the retina and nerve fibers of the optic nerve in the area of the lattice plate increased in degree of expression up to 180th days of the experiment. Conclusion. The results of electron microscopic studies of the intrabulbar part of the optic nerve in experimental animals in dynamics after the introduction of methyl alcohol indicate that the main trigger for the development of visual neuritis may be a violation of microcirculation processes in the retina and optic nerve, which leads to an increase in the permeability of the hematoneural barrier. These events entail dystrophic and destructive changes in the nervous tissue, the progression of which naturally leads, with the assistance of glial cells to gliofibrosis of the optic nerve. Keywords: toxic optic neuritis, methanol, hematoneural barrier, axon demyelination, gliofibrosis

How Tactile Afferents in the Human Fingerpad Encode Tangential Torques Associated with Manipulation: Are Monkeys Better than Us?

Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object orientation at grip surfaces. We investigated how torque information is encoded by human tactile afferents in the fingerpads and compared them to 97 afferents recorded in monkeys (n = 3; 2 females) in our previous study. Human data included slowly-adapting Type-II (SA-II) afferents, which are absent in the glabrous skin of monkeys. Torques of different magnitudes (3.5-7.5 mNm) were applied in clockwise and anticlockwise directions to a standard central site on the fingerpads of 34 human subjects (19 females). Torques were superimposed on a 2, 3, or 4 N background normal force. Unitary recordings were made from fast-adapting Type-I (FA-I, n = 39), and slowly-adapting Type-I (SA-I, n = 31) and Type-II (SA-II, n = 13) afferents supplying the fingerpads via microelectrodes inserted into the median nerve. All three afferent types encoded torque magnitude and direction, with torque sensitivity being higher with smaller normal forces. SA-I afferent responses to static torque were inferior to dynamic stimuli in humans, while in monkeys the opposite was true. In humans this might be compensated by the addition of sustained SA-II afferent input, and their capacity to increase or decrease firing rates with direction of rotation. We conclude that the discrimination capacity of individual afferents of each type was inferior in humans than monkeys which could be because of differences in fingertip tissue compliance and skin friction.SIGNIFICANCE STATEMENT We investigated how individual human tactile nerve fibers encode rotational forces (torques) and compared them to their monkey counterparts. Human hands, but not monkey hands, are innervated by a tactile neuron type (SA-II afferents) specialized to encode directional skin strain yet, so far, torque encoding has only been studied in monkeys. We find that human SA-I afferents were generally less sensitive and less able to discriminate torque magnitude and direction than their monkey counterparts, especially during the static phase of torque loading. However, this shortfall in humans could be compensated by SA-II afferent input. This indicates that variation in afferent types might complement each other signaling different stimulus features possibly providing computational advantage to discriminate stimuli.

Temporal contrast adaptation in the analysis of visual function in primary open-angle glaucoma

PurposeTo explore the utility of the recovery time (RT) after temporal contrast adaptation in primary open-angle glaucoma (POAG) visual function analysis, especially in severe and end-stage glaucoma, by the Erlanger Flicker Test (EFT).MethodsThis study included 80 POAG eyes (45 subjects) and 20 normal eyes (20 subjects). POAG eyes were divided into 5 groups. The diagnostic efficacy of the EFT was assessed, and the RT of POAG eyes at different stages was compared. The EFT results were compared with glaucomatous structure and function test results. A nomogram was developed to predict disease progression by the RT and structural indicators.ResultsIn the normal eyes, as the test contrast increased, the RT gradually decreased. The EFT test–retest reproducibility was good, with intraclass correlation coefficient values of 0.6 (P < 0.05) for each test contrast. At 12%, 25%, and 35% contrast, the RT in the severe and end-stage glaucoma eyes was significantly prolonged compared with the control group (P < 0.05). The RT at different contrasts was significantly correlated with visual acuity, mean defect, mean sensitivity, and general and individual quadrant optic nerve fiber layer thickness (P ≤ 0.001). The receiver operating curve indicated that RT12% showed the best overall area under the curve (0.863). We included RT25% and average optic nerve fiber layer thickness in constructing the nomogram. POAG eyes were further divided into 8 stages. According to the probability distribution, this model showed good performance for visual function analysis in advanced glaucoma.ConclusionsCombined with traditional glaucomatous structural and functional parameters, the EFT can be used in the diagnosis and visual function analysis of POAG, especially for severe and end-stage glaucoma. It could be a potential test for disease staging in severe and end-stage glaucoma.

Scatterometry Measurements With Scattered Light Imaging Enable New Insights Into the Nerve Fiber Architecture of the Brain

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 μm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.

Spatial modeling of epidermal nerve fiber patterns.

Peripheral neuropathy is a condition associated with poor nerve functionality. Epidermal nerve fiber (ENF) counts per epidermal surface are dramatically reduced and the two-dimensional (2D) spatial structure of ENFs tends to become more clustered as neuropathy progresses. Therefore, studying the spatial structure of ENFs is essential to fully understand the mechanisms that guide those morphological changes. In this article, we compare ENF patterns of healthy controls and subjects suffering from mild diabetic neuropathy by using suction skin blister specimens obtained from the right foot. Previous analysis of these data has focused on the analysis and modeling of the spatial ENF patterns consisting of the points where the nerves enter the epidermis, base points, and the points where the nerve fibers terminate, end points, projected on a 2D plane, regarding the patterns as realizations of spatial point processes. Here, we include the first branching points, the points where the nerve trees branch for the first time, and model the three-dimensional (3D) patterns consisting of these three types of points. To analyze the patterns, spatial summary statistics are used and a new epidermal active territory that measures the volume in the epidermis that is covered by the individual nerve fibers is constructed. We developed a model for both the 2D and the 3D patterns including the branching points. Also, possible competitive behavior between individual nerves is examined. Our results indicate that changes in the ENFs spatial structure can more easily be detected in the later parts of the ENFs.

Psychological stress induced bladder overactivity in female mice is associated with enhanced afferent nerve activity

Psychological stress has been linked to the development and exacerbation of overactive bladder symptoms, as well as afferent sensitisation in other organ systems. Therefore, we aimed to investigate the effects of water avoidance stress on bladder afferent nerve activity in response to bladder filling and pharmaceutical stimulation with carbachol and ATP in mice. Adult female C57BL/6J mice were exposed to either water avoidance stress (WAS) for 1 h/day for 10 days or normal housing conditions. Voiding behaviour was measured before starting and 24-h after final stress exposure and then animals were euthanised to measure afferent nerve activity in association with bladder compliance, spontaneous phasic activity, contractile responses, as well as release of urothelial mediators. WAS caused increased urinary frequency without affecting urine production. The afferent nerve activity at low bladder pressures (4–7 mmHg), relevant to normal physiological filling, was significantly increased after stress. Both low and high threshold nerves demonstrated enhanced activity at physiological bladder pressures. Urothelial ATP and acetylcholine release and bladder compliance were unaffected by stress as was the detrusor response to ATP (1 mM) and carbachol (1 µM). WAS caused enhanced activity of individual afferent nerve fibres in response bladder distension. The enhanced activity was seen in both low and high threshold nerves suggesting that stressed animals may experience enhanced bladder filling sensations at lower bladder volumes as well as increased pain sensations, both potentially contributing to the increased urinary frequency seen after stress.

Modeling Vagal Nerve Compound Action Potential Parameters to Control Specific Nerve Fiber Pathways

Neuromodulation of the peripheral nervous system has shown potential as an effective targeted therapy for conditions such as Parkinson's disease, chronic pain and gastroparesis. Stimulation of the vagus nerve is of particular interest since the nerve stretches from the brain to the colon, and parasympathetically controls nearly every organ in between. Thus, a detailed understanding of the vagus nerve morphologies and their ideal stimulation parameters is vital to delivering effective neuromodulation therapy with predictable and reproducible outcomes. The primary goal of this project is to utilize a recently developed compound action potential (CAP) modeling tool to characterize the interplay between four key parameters for bipolar vagal nerve recordings: stimulus pulse shape, cuff length, conduction distance, and peak amplitude of the resulting CAP volley. Sample data from the model's optimization tool is shown in Figures 1-2 below, indicating that the optimal cuff length and conduction distance for maximizing the CAP peak amplitude from bipolar recordings in the vagal ventral gastric branch ranges from 1-4 mm and 0-2 mm, respectively. This data was collected from a CAP model that corresponds to particular subsets of nerve fibers within the vagus nerve that supply individual organs, in this case the ventral gastric branch of the stomach. Further research will break down this CAP feedback to identify individual vagal nerve fiber pathways and their effect on linked organs, ultimately helping create more functional and targeted stimulation therapies.

Image motion with color contrast suffices to elicit an optokinetic reflex in Xenopus laevis tadpoles

The optokinetic reflex is a closed-loop gaze-stabilizing ocular motor reaction that minimizes residual retinal image slip during vestibulo-ocular reflexes. In experimental isolation, the reflex is usually activated by motion of an achromatic large-field visual background with strong influence of radiance contrast on visual motion estimation and behavioral performance. The presence of color in natural environments, however, suggests that chromatic cues of visual scenes provide additional parameters for image motion detection. Here, we employed Xenopus laevis tadpoles to study the influence of color cues on the performance of the optokinetic reflex and multi-unit optic nerve discharge during motion of a large-field visual scene. Even though the amplitude of the optokinetic reflex decreases with smaller radiance contrast, considerable residual eye movements persist at the ‘point of equiluminance’ of the colored stimuli. Given the color motion preferences of individual optic nerve fibers, the underlying computation potentially originates in retinal circuits. Differential retinal ganglion cell projections and associated ocular motor signal transformation might further reinforce the color dependency in conceptual correspondence with head/body optomotor signaling. Optokinetic reflex performance under natural light conditions is accordingly influenced by radiance contrast as well as by the color composition of the moving visual scene.

Spectral-domain OCT changes in retina and optic nerve in children with hypoxic\u2013ischaemic encephalopathy

PurposeTo evaluate the effect of neonatal hypoxic–ischaemic injury on the retina and the optic nerve and to correlate ocular damage with systemic parameters, laboratory tests, neurological imaging and therapeutic hypothermia at birth.MethodsForty-one children with hypoxic–ischaemic encephalopathy (HIE) at birth (9.09 ± 3.78 years) and a control group of 38 healthy subjects (9.57 ± 3.47 years) were enrolled in a cohort study. The HIE population was divided into three subgroups, based on the degree of encephalopathy according to Sarnat score and the treatment with therapeutic hypothermia (TH): Sarnat score I not treated with hypothermia, Sarnat score II-III treated with TH and Sarnat score II-III not subjected to TH. Total macular thickness, individual retinal layers and peripapillary nerve fibre layer thickness were measured with spectral-domain optical coherence tomography. Clinical data of perinatal period of HIE children were collected: APGAR score, pH and base excess of funiculus blood at birth, apnoea duration, brain ultrasound, cerebral MRI ischaemic lesions and blood chemistry tests.ResultsChildren with Sarnat score I did not show a reduction of peripapillary nerve fibres and ganglion cell layer compared to the control group (p = 0.387, p = 0.316). Peripapillary nerve fibre layer was 109.06 ± 7.79 μm in children with Sarnat score II-III treated with TH, 108.31 ± 7.83 μm in subjects with Sarnat score II-III not subjected to TH and 114.27 ± 6.81 μm in the control group (p = 0.028, p = 0.007). Ganglion cell layer was thinner in children with Sarnat score II-III treated with TH (50.31 ± 5.13 μm) compared to the control group (54.04 ± 2.81 μm) (p = 0.01). Inner retinal layers damage correlated with C-reactive protein and lactate dehydrogenase increase, while higher levels of total bilirubin were protective against retinal impairment (p < 0.05). Cerebral oedema was related to peripapillary nerve fibre layer damage (p = 0.046).ConclusionsThickness reduction of inner retinal layer and peripapillary nerve fibre impairment was related to encephalopathy severity. Ocular damage was associated with inflammation and cerebral oedema following hypoxic–ischaemic damage.

Multicolor sparse viral labeling and 3D digital tracing of enteric plexus in mouse proximal colon using a novel adeno‐associated virus capsid

AbstractBackgroundIntravenous administration of adeno‐associated virus (AAV) can be used as a noninvasive approach to trace neuronal morphology and links. AAV‐PHP.S is a variant of AAV9 that effectively transduces the peripheral nervous system. The objective was to label randomly and sparsely enteric plexus in the mouse colon using AAV‐PHP.S with a tunable two‐component multicolor vector system and digitally trace individual neurons and nerve fibers within microcircuits in three dimensions (3D).MethodsA vector system including a tetracycline inducer with a tet‐responsive element driving three separate fluorophores was packaged in the AAV‐PHP.S capsid. The vectors were injected retro‐orbitally in mice, and the colon was harvested 3 weeks after. Confocal microscopic images of enteric plexus were digitally segmented and traced in 3D using Neurolucida 360, neuTube, or Imaris software.Key ResultsThe transduction of multicolor AAV vectors induced random sparse spectral labeling of soma and neurites primarily in the myenteric plexus of the proximal colon, while neurons in the submucosal plexus were occasionally transduced. Digital tracing in 3D showed various types of wiring, including multiple conjunctions of one neuron with other neurons, neurites en route, and endings; clusters of neurons in close apposition between each other; axon–axon parallel conjunctions; and intraganglionic nerve endings consisting of multiple nerve endings and passing fibers. Most of digitally traced neuronal somas were of small or medium in size.Conclusions &amp; InferencesThe multicolor AAV‐PHP.S‐packaged vectors enabled random sparse spectral labeling and revealed complexities of enteric microcircuit in the mouse proximal colon. The techniques can facilitate digital modeling of enteric micro‐circuitry.

Simulating bidirectional peripheral neural interfaces in EIDORS.

Bioelectronic neural interfaces that deliver adaptive therapeutic stimulation in an intelligent manner must be able to sense and stimulate activity within the same nerve. Existing minimally-invasive peripheral neural interfaces can provide a read-out of the aggregate level of activity via electrical recordings of nerve activity, but these recordings are limited in terms of their specificity. Computational simulations can provide fine-grained insight into the contributions of different neural populations to the extracellular recording, but integration of the signals from individual nerve fibers requires knowledge of spread of current in the complex (heterogenous, anisotropic) extracellular space. We have developed a model which uses the open-source EIDORS package for extracellular stimulation and recording in the pelvic nerve. The pelvic nerve is the primary source of autonomic innervation to the pelvic organs, and a prime target for electrical stimulation to treat a variety of voiding disorders. We simulated recordings of spontaneous and electrically-evoked activity using biophysical models for myelinated and unmyelinated axons. As expected, stimulus thresholds depended strongly on both fibre type and electrode-fibre distance. In conclusion, EIDORS can be used to accurately simulate extracellular recording in complex, heterogenous neural geometries.

Volume gradients in inner hair cell-auditory nerve fiber pre- and postsynaptic proteins differ across mouse strains

In different animal models, auditory nerve fibers display variation in spontaneous activity and response threshold. Functional and structural differences among inner hair cell ribbon synapses are believed to contribute to this variation. The relative volumes of synaptic proteins at individual synapses might be one such difference. This idea is based on the observation of opposing volume gradients of the presynaptic ribbons and associated postsynaptic glutamate receptor patches in mice along the pillar modiolar axis of the inner hair cell, the same axis along which fibers were shown to vary in their physiological properties. However, it is unclear whether these opposing gradients are expressed consistently across animal models. In addition, such volume gradients observed for separate populations of presynaptic ribbons and postsynaptic glutamate receptor patches suggest different relative volumes of these synaptic structures at individual synapses; however, these differences have not been examined in mice. Furthermore, it is unclear whether such gradients are limited to these synaptic proteins. Therefore, we analyzed organs of Corti isolated from CBA/CaJ, C57BL/6, and FVB/NJ mice using immunofluorescence, confocal microscopy, and quantitative image analysis. We find consistent expression of presynaptic volume gradients across strains of mice and inconsistent expression of postsynaptic volume gradients. We find differences in the relative volume of synaptic proteins, but these are different between CBA/CaJ mice, and C57BL/6 and FVB/NJ mice. We find similar results in C57BL/6 and FVB/NJ mice when using other postsynaptic density proteins (Shank1, Homer, and PSD95). These results have implications for the mechanisms by which volumes of synaptic proteins contribute to variations in the physiology of individual auditory nerve fibers and their vulnerability to excitotoxicity.

Calbindin Immunoreactivity in Rat Cerebral Cortex and Cerebellum Neurons

Objective. To carry out an immunohistochemical assessment of the distribution of calbindin D28K in cerebral cortex (parietal and frontal) and cerebellum neurons in rats.Materials and methods. Experiments were performed on 18 mongrel white male rats weighing 200–250 g. Fragments of the frontal and parietal cortex and cerebellar cortex were collected. Paraffi n sections were processed using primary polyclonal antibodies to detect calbindin D28K immunoreactivity.Results. In layer II of the frontal and parietal cortex, most neurons were moderately immunopositive, while layers III, V, and VI contained occasional neurons with high calbindin immunoreactivity. Individual nerve fibers, mainly the dendrites of pyramidal neurons, were clearly seen. Some of these showed a distinctive staining pattern: immunopositive parts alternated with immunonegative parts. In the cerebellar cortex, the bodies and dendritic branches of Purkinje cells were well stained. A significant proportion of neurons in the granular layer were moderately immunopositive, and included some afferent nerve fibers running from the white matter.Conclusions. Calbindin immunoreactivity in cerebral cortex structures in normal rats varied significantly and could be related both to the type of neuron and their functional state.

Anatomy of the Proboscideal Nerve in the Proboscis of the African Elephant (Loxodonta africana)

The elephant proboscis (i.e., trunk), a unique muscular organ formed by the combined narial and upper lip region, is a complex muscular hydrostat adapted for a multitude of functions, including grasping, holding, and transporting objects, siphoning, holding, and spraying water, and communication. The proboscis has previously been described as containing tens of thousands of muscle fascicles, each working individually to help bend, curve, and curl the trunk in all directions at any point along its length. Although the muscular system of the proboscis has previously been described in some depth, the unique nervous innervation of the proboscis has been given minimal attention. Here, the previously frozen head of an adult female African elephant (Loxodonta africana) is dissected to investigate the anatomy of the neuromuscular anatomy of the proboscis in more depth. In addition to the complexity of interlacing muscle fascicles and the integrated connective tissues, we identified the proboscideal nerve, a large, 2.5 to 3 centimeter thick nerve that is unique to elephants. The proboscideal nerve is made up of the combined distal nerve fibers of the infraorbital branch of the maxillary nerve (CN V3) and zygomatic branch of the facial nerve (CN VII). Specifically, as the infraorbital branch of the maxillary nerve (carrying sensory innervation) exits the cranium through the infraorbital foramen, the zygomatic branch of the facial nerve (carrying motor innervation) runs along the ventral border of the zygomatic arch and joins the maxillary nerve rostrodorsal to the masseter muscle to form the proboscideal nerve. The proboscideal nerve then travels down the length of the proboscis transmitting small sensory and motor nerve fibers to all muscle fascicles and surrounding skin and tissue. Given this anatomy, fine‐tuned neuromuscular control and coordination of the individual nerve fibers are necessary to control the diverse movements that occur throughout the length of the proboscis. This specialized evolutionary adaptation helped shape a functionally innovative organ that grew, modified, and persisted throughout the course of proboscidean evolution.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The terminal hypoglossal nerve and its anatomical variability

Upper airway stimulation plays an increasingly important role in the treatment of obstructive sleep apnea (OSA). The target of stimulation is the hypoglossal nerve (N.XII), which-as apure motor nerve-innervates the intrinsic and extrinsic tongue muscles. By selectively stimulating individual nerve fibers, the upper airway can be opened by protruding the tongue. The N.XII has anumber of anatomical variants, which are decisive during surgical implantation of these pacemaker systems. Intraoperative neuromonitoring is very helpful in this regard. Accurate placement of the stimulation electrode for selective upper airway stimulation requires knowledge of N.XII anatomy, intraoperative neuromonitoring, and accurate assessment of muscle contractions and tongue movements.

Real-Time Prosthetic Digit Actuation by Optical Read-out of Activity-Dependent Calcium Signals in an Ex Vivo Peripheral Nerve.

Improved neural interfacing strategies are needed for the full articulation of advanced prostheses. To address limitations of existing control interface designs, the work of our laboratory has presented an optical approach to reading activity from individual nerve fibers using activity-dependent calcium transients. Here, we demonstrate the feasibility of such signals to control prosthesis actuation by using the axonal fluorescence signal in an ex vivo mouse nerve to drive a prosthetic digit in real-time. Additionally, signals of varying action potential frequency are streamed post hoc to the prosthesis, showing graded motor output and the potential for proportional neural control. This proof-of-concept work is a novel demonstration of the functional use of activity-dependent optical read-out in the nerve.

Test-retest reliability of wrist joint position sense in healthy adults in a clinical setting

Intra-neural microstimulation (INMS) is a technique that allows the precise delivery of low-current electrical pulses into human peripheral nerves. Single unit INMS can be used to stimulate individual afferent nerve fibres during microneurography. Combining this with neuroimaging allows the unique monitoring of central nervous system activation in response to unitary, controlled tactile input, with functional magnetic resonance imaging (fMRI) providing exquisite spatial localisation of brain activity and magnetoencephalography (MEG) high temporal resolution.INMS systems suitable for use within electrophysiology laboratories have been available for many years. We describe an INMS system specifically designed to provide compatibility with both ultra-high field (7 T) fMRI and MEG. Numerous technical and safety issues are addressed. The system is fully analogue, allowing for arbitrary frequency and amplitude INMS stimulation.Unitary recordings obtained within both the MRI and MEG screened-room environments are comparable with those obtained in ‘clean’ electrophysiology recording environments. Single unit INMS (current <7 μA, 200 μs pulses) of individual mechanoreceptive afferents produces appropriate and robust responses during fMRI and MEG.This custom-built MRI- and MEG-compatible stimulator overcomes issues with existing INMS approaches; it allows well-controlled switching between recording and stimulus mode, prevents electrical shocks because of long cable lengths, permits unlimited patterns of stimulation, and provides a system with improved work-flow and participant comfort.We demonstrate that the requirements for an INMS-integrated system, which can be used with both fMRI and MEG imaging systems, have been fully met.