Intraneural ultramicroelectrode arrays for function-specific interfacing to the vagus nerve.
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ABSTRACT:
SUBMITTER: Ghazavi A
PROVIDER: S-EPMC7654841 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Autonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8-9 µm in diameter, 150-250 µm in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1-91.7 µV and signal-to-noise ratios of 2.0-8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7-4.4 m/s) and efferent (0.7-8.8 m/s) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.
| S-EPMC7511947 | biostudies-literature
Project description:The axons of the sensory, or afferent, vagus nerve transmit action potentials to the central nervous system in response to changes in the body's metabolic and physiological status. Recent advances in identifying neural circuits that regulate immune responses to infection, inflammation and injury have revealed that vagus nerve signals regulate the release of cytokines and other factors produced by macrophages. Here we record compound action potentials in the cervical vagus nerve of adult mice and reveal the specific activity that occurs following administration of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin 1? (IL-1?). Importantly, the afferent vagus neurograms generated by TNF exposure are abolished in double knockout mice lacking TNF receptors 1 and 2 (TNF-R1/2KO), whereas IL-1?-specific neurograms are eliminated in knockout mice lacking IL-1? receptor (IL-1RKO). Conversely, TNF neurograms are preserved in IL-1RKO mice, and IL-1? neurograms are unchanged in TNF-R1/2KO mice. Analysis of the temporal dynamics and power spectral characteristics of afferent vagus neurograms for TNF and IL-1? reveals cytokine-selective signals. The nodose ganglion contains the cell bodies of the sensory neurons whose axons run through the vagus nerve. The nodose neurons express receptors for TNF and IL-1?, and we show that exposing them to TNF and IL-1? significantly stimulates their calcium uptake. Together these results indicate that afferent vagus signals in response to cytokines provide a basic model of nervous system sensing of immune responses.
| S-EPMC6039192 | biostudies-literature
Project description:Pairing sensory or motor events with vagus nerve stimulation (VNS) can reorganize sensory or motor cortex. Repeatedly pairing a tone with a brief period of VNS increases the proportion of primary auditory cortex (A1) responding to the frequency of the paired tone. However, the relationship between VNS intensity and cortical map plasticity is not known.The primary goal of this study was to determine the range of VNS intensities that can be used to direct cortical map plasticity.The rats were exposed to a 9?kHz tone paired with VNS at intensities of 0.4, 0.8, 1.2, or 1.6?mA.In rats that received moderate (0.4-0.8?mA) intensity VNS, 75% more cortical neurons were tuned to frequencies near the paired tone frequency. A two-fold effective range is broader than expected based on previous VNS studies. Rats that received high (1.2-1.6?mA) intensity VNS had significantly fewer neurons tuned to the same frequency range compared to the moderate intensity group.This result is consistent with previous results documenting that VNS is memory enhancing as a non-monotonic relationship of VNS intensity.
| S-EPMC4724352 | biostudies-literature
Project description:BACKGROUND:Glomus tumors in the digital nerve are extremely rare. Multiple intraneural glomus tumors in different digital nerve fascicles have not been previously reported. CASE PRESENTATION:We report the case of a 54-year-old male with a 1-year history of progressive numbness of the middle finger with point tenderness at the level of the middle phalanx. Surgical incision revealed the presence of two glomus tumors within different fascicles of the ulnar digital nerve of the middle finger. One tumor was excised along with surrounding fascicle, the other was removed leaving the fascicle intact. Subsequently, the patient regained function of the finger and no tumors have recurred. CONCLUSIONS:Patients and physicians should be aware of the properties of intraneural glomus tumors so that early diagnosis and treatment can be sought.
| S-EPMC6729111 | biostudies-literature
Project description:Background:Glucose is a crucial energy source. In humans, it is the primary sugar for high energy demanding cells in brain, muscle and peripheral neurons. Deviations of blood glucose levels from normal levels for an extended period of time is dangerous or even fatal, so regulation of blood glucose levels is a biological imperative. The vagus nerve, comprised of sensory and motor fibres, provides a major anatomical substrate for regulating metabolism. While prior studies have implicated the vagus nerve in the neurometabolic interface, its specific role in either the afferent or efferent arc of this reflex remains elusive. Methods:Here we use recently developed methods to isolate and decode specific neural signals acquired from the surface of the vagus nerve in BALB/c wild type mice to identify those that respond robustly to hypoglycemia. We also attempted to decode neural signals related to hyperglycemia. In addition to wild type mice, we analyzed the responses to acute hypo- and hyperglycemia in transient receptor potential cation channel subfamily V member 1 (TRPV1) cell depleted mice. The decoding algorithm uses neural signals as input and reconstructs blood glucose levels. Results:Our algorithm was able to reconstruct the blood glucose levels with high accuracy (median error 18.6?mg/dl). Hyperglycemia did not induce robust vagus nerve responses, and deletion of TRPV1 nociceptors attenuated the hypoglycemia-dependent vagus nerve signals. Conclusion:These results provide insight to the sensory vagal signaling that encodes hypoglycemic states and suggest a method to measure blood glucose levels by decoding nerve signals. Trial registration:Not applicable.
| S-EPMC7098244 | biostudies-literature
Project description:BackgroundIndividuals with communication disorders, such as aphasia, exhibit weak auditory cortex responses to speech sounds and language impairments. Previous studies have demonstrated that pairing vagus nerve stimulation (VNS) with tones or tone trains can enhance both the spectral and temporal processing of sounds in auditory cortex, and can be used to reverse pathological primary auditory cortex (A1) plasticity in a rodent model of chronic tinnitus.Objective/hypothesisWe predicted that pairing VNS with speech sounds would strengthen the A1 response to the paired speech sounds.MethodsThe speech sounds 'rad' and 'lad' were paired with VNS three hundred times per day for twenty days. A1 responses to both paired and novel speech sounds were recorded 24 h after the last VNS pairing session in anesthetized rats. Response strength, latency and neurometric decoding were compared between VNS speech paired and control rats.ResultsOur results show that VNS paired with speech sounds strengthened the auditory cortex response to the paired sounds, but did not strengthen the amplitude of the response to novel speech sounds. Responses to the paired sounds were faster and less variable in VNS speech paired rats compared to control rats. Neural plasticity that was specific to the frequency, intensity, and temporal characteristics of the paired speech sounds resulted in enhanced neural detection.ConclusionVNS speech sound pairing provides a novel method to enhance speech sound processing in the central auditory system. Delivery of VNS during speech therapy could improve outcomes in individuals with receptive language deficits.
| S-EPMC4461522 | biostudies-literature
Project description:The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1? and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1? and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1? in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1? and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1?-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1?, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve.
| S-EPMC6003492 | biostudies-literature
Project description:To find inflammatory signatures in post mortem vagus nerves of COVID-19 patients in comparisin to non-infected controls.
2023-08-21 | GSE233732 | GEO
Project description:We report the fabrication and characterization of microwell-based individually addressable microelectrode arrays (MEAs) and their application to spatially and temporally resolved detection of neurotransmitter release across a single pheochromocytoma (PC12) cell. The microwell-based MEAs consist of 16 4-?m-width square ultramicroelectrodes, 25 3-?m-width square ultramicroelectrodes, or 36 2-?m-width square ultramicroelectrodes, all inside a 40 × 40 ?m square SU-8 microwell. MEAs were fabricated on glass substrates by photolithography, thin film deposition, and reactive ion etching. The ultramicroelectrodes in each MEA are tightly defined in a 30 × 30 ?m square area, which is further encased inside the SU-8 microwell. With this method, we demonstrate that these microelectrodes are stable, reproducible, and demonstrate good electrochemical properties using cyclic voltammetry. Effective targeting and culture of a single cell is achieved by combining cell-sized microwell trapping and cell-picking micropipet techniques. The surface of the microelectrodes in the MEA was coated with collagen IV to promote cell adhesion and further single-cell culture, as good adhesion between the cell membrane and the electrode surface is critical for the quality of the measurements. Imaging the spatial distribution of exocytosis at the surface of a single PC12 cell has also been demonstrated with this system. Exocytotic signals have been successfully recorded from eight independent 2-?m-wide ultramicroelectrodes from a single PC12 cell showing that the subcellular heterogeneity in single-cell exocytosis can be precisely analyzed with these microwell-based MEAs.
| S-EPMC4014142 | biostudies-literature
Project description:The efferent dorsal motor nucleus of the vagal nuclei complex may degenerate early in the course of Parkinson's disease (PD), while efferent nucleus ambiguous, the principal source of parasympathetic vagal neurons innervating the heart, and afferent somatosensory nuclei remain intact.To obtain neurophysiological evidence related to this pattern, we tested processing of afferent sensory information transmitted via the auricular branch of the vagus nerve (ABVN) which is known to be connected to autonomic regulation of cardiac rhythm.In this cross-sectional observational study, we recorded (i) somatosensory evoked potentials (ABVN-SEP) and (ii) cutaneo-cardioautonomic response elicited by stimulation of the ABVN (modulation of heart-rate variability (HRV index; low frequency power, ln(LF), high frequency power, ln(HF); ln(LF/HF) ratio)) in 50 PD patients and 50 age and sex matched healthy controls. Additionally, auditory evoked potentials and trigeminal nerve SEP were assessed.Neither ABVN-SEP nor any of the other functional brainstem parameters differed between patients and controls. Although HRV index was decreased in PD patients, modulation of ln(LF/HF) by ABVN-stimulation, likely indicating cardiac parasympathetic activation, did not differ between both groups.Findings do not point to prominent dysfunction of processing afferent information from ABVN and its connected parasympathetic cardiac pathway in PD. They are consistent with the known pattern of degeneration of the vagal nuclei complex of the brainstem.
| S-EPMC4388709 | biostudies-literature