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"Action Potentials"
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Novel electrode technologies for neural recordings
Neural recording electrode technologies have contributed considerably to neuroscience by enabling the extracellular detection of low-frequency local field potential oscillations and high-frequency action potentials of single units. Nevertheless, several long-standing limitations exist, including low multiplexity, deleterious chronic immune responses and long-term recording instability. Driven by initiatives encouraging the generation of novel neurotechnologies and the maturation of technologies to fabricate high-density electronics, novel electrode technologies are emerging. Here, we provide an overview of recently developed neural recording electrode technologies with high spatial integration, long-term stability and multiple functionalities. We describe how these emergent neurotechnologies can approach the ultimate goal of illuminating chronic brain activity with minimal disruption of the neural environment, thereby providing unprecedented opportunities for neuroscience research in the future.Here, Hong and Lieber review recent developments in electrode technologies for the recording of single-unit spiking activity. They focus on advances in electrodes with high spatial integration, long-term stability and multifunctional capacities.
Journal Article
Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy
BackgroundFew interventions reduce patellar tendinopathy (PT) pain in the short term. Eccentric exercises are painful and have limited effectiveness during the competitive season. Isometric and isotonic muscle contractions may have an immediate effect on PT pain.MethodsThis single-blinded, randomised cross-over study compared immediate and 45 min effects following a bout of isometric and isotonic muscle contractions. Outcome measures were PT pain during the single-leg decline squat (SLDS, 0–10), quadriceps strength on maximal voluntary isometric contraction (MVIC), and measures of corticospinal excitability and inhibition. Data were analysed using a split-plot in time-repeated measures analysis of variance (ANOVA).Results6 volleyball players with PT participated. Condition effects were detected with greater pain relief immediately from isometric contractions: isometric contractions reduced SLDS (mean±SD) from 7.0±2.04 to 0.17±0.41, and isotonic contractions reduced SLDS (mean±SD) from 6.33±2.80 to 3.75±3.28 (p<0.001). Isometric contractions released cortical inhibition (ratio mean±SD) from 27.53%±8.30 to 54.95%±5.47, but isotonic contractions had no significant effect on inhibition (pre 30.26±3.89, post 31.92±4.67; p=0.004). Condition by time analysis showed pain reduction was sustained at 45 min postisometric but not isotonic condition (p<0.001). The mean reduction in pain scores postisometric was 6.8/10 compared with 2.6/10 postisotonic. MVIC increased significantly following the isometric condition by 18.7±7.8%, and was significantly higher than baseline (p<0.001) and isotonic condition (p<0.001), and at 45 min (p<0.001).ConclusionsA single resistance training bout of isometric contractions reduced tendon pain immediately for at least 45 min postintervention and increased MVIC. The reduction in pain was paralleled by a reduction in cortical inhibition, providing insight into potential mechanisms. Isometric contractions can be completed without pain for people with PT. The clinical implications are that isometric muscle contractions may be used to reduce pain in people with PT without a reduction in muscle strength.
Journal Article
Relative contributions of different neural sources to the EEG
•Action potentials account for approximately 20% of the EEG signal generator.•L5 PCs are the dominant contributor to the EEG.•Action potentials are sufficient to generate physiological oscillations in the EEG.
Dogma dictates that the EEG signal is generated by postsynaptic currents (PSCs) because there are an enormous number of synapses in the brain, and PSCs have relatively long durations. However, PSCs are not the only potential source of electric fields in the brain. Action potentials, afterpolarizations, and presynaptic activity can also generate electric fields. Experimentally it is exceedingly difficult to delineate the contributions of different sources because they are casually linked. However, using computational modeling, we can interrogate the relative contributions of different neural elements to the EEG. We used a library of neuron models with morphologically realistic axonal arbors to quantify the relative contributions of PSCs, action potentials, and presynaptic activity to the EEG signal. Consistent with prior assertions, PSCs were the largest contributor to the EEG, but action potentials and afterpolarizations can also make appreciable contributions. For a population of neurons generating simultaneous PSCs and action potentials, we found that the action potentials accounted for up to 20% of the source strength while PSCs accounted for the other 80% and presynaptic activity negligibly contributed. Additionally, L5 PCs generated the largest PSC and action potential signals indicating that they the dominant EEG signal generator. Further, action potentials and afterpolarizations were sufficient to generate physiological oscillations, indicating that they are valid source contributors to the EEG. The EEG emerges from a combination of multiple different source, and, while PSCs are the largest contributor, other sources are non-negligible and should be included in modeling, analysis and interpretation of the EEG.
Journal Article
Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps
Abstract
Background and Aims
Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans.
Methods
A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode.
Key Results
Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested.
Conclusions
Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia.
Journal Article
SpikeInterface, a unified framework for spike sorting
Much development has been directed toward improving the performance and automation of spike sorting. This continuous development, while essential, has contributed to an over-saturation of new, incompatible tools that hinders rigorous benchmarking and complicates reproducible analysis. To address these limitations, we developed SpikeInterface, a Python framework designed to unify preexisting spike sorting technologies into a single codebase and to facilitate straightforward comparison and adoption of different approaches. With a few lines of code, researchers can reproducibly run, compare, and benchmark most modern spike sorting algorithms; pre-process, post-process, and visualize extracellular datasets; validate, curate, and export sorting outputs; and more. In this paper, we provide an overview of SpikeInterface and, with applications to real and simulated datasets, demonstrate how it can be utilized to reduce the burden of manual curation and to more comprehensively benchmark automated spike sorters.
Journal Article
Regulation of developing myelin sheath elongation by oligodendrocyte calcium transients in vivo
How action potentials regulate myelination by oligodendrocytes is uncertain. We show that neuronal activity raises [Ca2+]i in developing oligodendrocytes in vivo and that myelin sheath elongation is promoted by a high frequency of [Ca2+]i transients and prevented by [Ca2+]i buffering. Sheath elongation occurs ~1 h after [Ca2+]i elevation. Sheath shortening is associated with a low frequency of [Ca2+]i transients but with longer duration [Ca2+]i bursts. Thus, [Ca2+]i controls myelin sheath development.
Journal Article
The claustrum coordinates cortical slow-wave activity
During sleep and awake rest, the neocortex generates large-scale slow-wave (SW) activity. Here, we report that the claustrum coordinates neocortical SW generation. We established a transgenic mouse line that enabled the genetic interrogation of a subpopulation of claustral glutamatergic neurons. These neurons received inputs from and sent outputs to widespread neocortical areas. The claustral neuronal firings mostly correlated with cortical SW activity. In vitro optogenetic stimulation of the claustrum induced excitatory postsynaptic responses in most neocortical neurons, but elicited action potentials primarily in inhibitory interneurons. In vivo optogenetic stimulation induced a synchronized down-state featuring prolonged silencing of neural activity in all layers of many cortical areas, followed by a down-to-up state transition. In contrast, genetic ablation of claustral neurons attenuated SW activity in the frontal cortex. These results demonstrate a crucial role of claustral neurons in synchronizing inhibitory interneurons across wide cortical areas for the spatiotemporal coordination of SW activity.The authors establish the claustrum-Cre transgenic mouse line and demonstrate that the claustrum orchestrates cortical slow-wave activity by synchronously driving the inhibitory interneurons in widespread cortical areas.
Journal Article
Neurophysiological outcomes that sustained clinically significant improvements over 3 years of physiologic ECAP-controlled closed-loop spinal cord stimulation for the treatment of chronic pain
IntroductionA novel, spinal cord stimulation (SCS) system with a physiologic closed-loop (CL) feedback mechanism controlled by evoked compound action potentials (ECAPs) enables the optimization of physiologic neural dose and the accuracy of the stimulation, not possible with any other commercially available SCS systems. The report of objective spinal cord measurements is essential to increase the transparency and reproducibility of SCS therapy. Here, we report a cohort of the EVOKE double-blind randomized controlled trial treated with CL-SCS for 36 months to evaluate the ECAP dose and accuracy that sustained the durability of clinical improvements.Methods41 patients randomized to CL-SCS remained in their treatment allocation and were followed up through 36 months. Objective neurophysiological data, including measures of spinal cord activation, were analyzed. Pain relief was assessed by determining the proportion of patients with ≥50% and ≥80% reduction in overall back and leg pain.ResultsThe performance of the feedback loop resulted in high-dose accuracy by keeping the elicited ECAP within 4µV of the target ECAP set on the system across all timepoints. Percent time stimulating above the ECAP threshold was >98%, and the ECAP dose was ≥19.3µV. Most patients obtained ≥50% reduction (83%) and ≥80% reduction (59%) in overall back and leg pain with a sustained response observed in the rates between 3-month and 36-month follow-up (p=0.083 and p=0.405, respectively).ConclusionThe results suggest that a physiological adherence to supra-ECAP threshold therapy that generates pain inhibition provided by ECAP-controlled CL-SCS leads to durable improvements in pain intensity with no evidence of loss of therapeutic effect through 36-month follow-up.
Journal Article
Thermal constraints on in vivo optogenetic manipulations
A key assumption of optogenetics is that light only affects opsin-expressing neurons. However, illumination invariably heats tissue, and many physiological processes are temperature-sensitive. Commonly used illumination protocols increased the temperature by 0.2–2 °C and suppressed spiking in multiple brain regions. In the striatum, light delivery activated an inwardly rectifying potassium conductance and biased rotational behavior. Thus, careful consideration of light-delivery parameters is required, as even modest intracranial heating can confound interpretation of optogenetic experiments.
Journal Article