Single Action Potentials Research Articles

Tracking individual action potentials throughout mammalian axonal arbors.

Axons are neuronal processes specialized for conduction of action potentials (APs). The timing and temporal precision of APs when they reach each of the synapses are fundamentally important for information processing in the brain. Due to small diameters of axons, direct recording of single AP transmission is challenging. Consequently, most knowledge about axonal conductance derives from modeling studies or indirect measurements. We demonstrate a method to noninvasively and directly record individual APs propagating along millimeter-length axonal arbors in cortical cultures with hundreds of microelectrodes at microsecond temporal resolution. We find that cortical axons conduct single APs with high temporal precision (~100 µs arrival time jitter per mm length) and reliability: in more than 8,000,000 recorded APs, we did not observe any conduction or branch-point failures. Upon high-frequency stimulation at 100 Hz, successive became slower, and their arrival time precision decreased by 20% and 12% for the 100th AP, respectively.

Quantal Fluctuations in Central Mammalian Synapses: Functional Role of Vesicular Docking Sites.

Quantal fluctuations are an integral part of synaptic signaling. At the frog neuromuscular junction, Bernard Katz proposed that quantal fluctuations originate at "reactive sites" where specific structures of the presynaptic membrane interact with synaptic vesicles. However, the physical nature of reactive sites has remained unclear, both at the frog neuromuscular junction and at central synapses. Many central synapses, called simple synapses, are small structures containing a single presynaptic active zone and a single postsynaptic density of receptors. Several lines of evidence indicate that simple synapses may release several synaptic vesicles in response to a single action potential. However, in some synapses at least, each release event activates a significant fraction of the postsynaptic receptors, giving rise to a sublinear relation between vesicular release and postsynaptic current. Partial receptor saturation as well as synaptic jitter gives to simple synapse signaling the appearance of a binary process. Recent investigations of simple synapses indicate that the number of released vesicles follows binomial statistics, with a maximum reflecting the number of docking sites present in the active zone. These results suggest that at central synapses, vesicular docking sites represent the reactive sites proposed by Katz. The macromolecular architecture and molecular composition of docking sites are presently investigated with novel combinations of techniques. It is proposed that variations in docking site numbers are central in defining intersynaptic variability and that docking site occupancy is a key parameter regulating short-term synaptic plasticity.

P 157 Detection radius of EMG for fasciculations: combined ultrasonographic-electromyographic analysis

Background Fasciculations are caused by spontaneous discharges of single motor units. In electromyography (EMG), they are characterized by single motor unit action potentials. Muscle ultrasonography is increasingly applied as a non-invasive screening tool for the examination of fasciculations. In the context of motor neuron disease, the sensitivity of muscle ultrasonography to detect fasciculations was superior to EMG. Limited detection radius of concentric needle EMG may explain this discrepancy, but a direct EMG-ultrasonography-correlation of single fasciculations has not been reported so far. In the current study, we aimed to define an “EMG detection radius” of fasciculations by simultaneous recording of EMG and muscle ultrasonography. Methods Parallel to concentric needle EMG, we recorded in-plane high-resolution videos of muscle ultrasonography showing the needle tip within the transverse section of the muscle. A total of 200 fasciculations were acquired during 50 recordings of 10 patients with motor neuron disease. Amplitude and duration of EMG fasciculation potentials were subsequently correlated to the corresponding ultrasonographic muscle displacement and the distance from the EMG needle tip. Results The onset of ultrasonographic muscle displacement was concurrent to its EMG fasciculation potential whereas the plateau phase and the backward movement occurred when the EMG had already returned to baseline. About 40% of fasciculations observed on ultrasonography were not detected in EMG and this included fasciculations located close to the needle tip. The amplitude of EMG-positive fasciculations was negatively correlated to their distance from the needle tip. However, the correlation differed significantly between different patients and between different muscles. Discussion Analysis of fasciculations on simultaneous EMG and ultrasonography recordings improves the understanding of the “EMG-detection radius” of fasciculations. A relevant portion of ultrasonographic fasciculations was not detected on EMG which may in part explain the superior sensitivity of ultrasonography. Different localization of neuromuscular endplates and of myofibrils along the longitudinal axis of the analyzed muscles might explain the occurrence of “EMG-negative” fasciculations. Alternatively, muscle remodeling or changes of axon terminals due to neurodegeneration may alter the sensitivity of EMG. Further studies are needed to classify fasciculations of other entities with this method.

Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells.

Neural computation is performed by transforming input signals into sequences of action potentials (APs), which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na+ entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na+ entry efficiency of somatic AP. Activating inward Ca2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca2+-activated outward K+ current in dendrites, however, decreases Na+ entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na+ influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption.

Effects of a combination of 3,4-methylenedioxymeth amphetamine and caffeine on real time stimulated dopamine release in the rat striatum: Studies using fast cyclic voltammetry

It is well documented that caffeine exacerbates the hyperthermia associated with acute exposure to 3,4-methylenedioxymethamphetamine (MDMA) in rats. Previous reports have also indicated that MDMA-related enhancement of dopamine release is exacerbated in the presence of caffeine. In the present study we have examined whether the effects of MDMA on real-time stimulated dopamine release, in the absence of uptake inhibition, are accentuated in the presence of caffeine. Isolated striatal slices from adult male Wistar rats were treated acutely with MDMA, caffeine, or a combination, and their effects on single and 5pulse stimulated dopamine release monitored using the technique of fast cyclic voltammetry. Caffeine at 10 or 100μM had no significant effect on single pulse stimulated dopamine release. However 100μM caffeine caused a significant peak increase in 5pulse stimulated dopamine release. Both 1 and 30μM MDMA gave rise to a significant increase in both single and 5-pulse dopamine release and reuptake. A combination of 100μM caffeine and 1 or 30μM MDMA did not significantly enhance the effects of MDMA on single or 5pulse dopamine release and reuptake when compared to that applied alone. Utilizing single action potential dependent dopamine release, these results do not demonstrate a caffeine-enhanced MDMA-induced dopamine release.

P340 The MUNE method as a complementary test to routine EMG in amyotrophic lateral sclerosis

Electromyographic (EMG) abnormalities that reveal denervation and reinnervation caused by lower motor neuron degeneration do not reflect the number of motor units that determines muscle strength. Consequently, motor unit activity potential (MUAP) parameters do not reflect muscle dysfunction. Objectives The aim of the study was to compare the value of motor unit number estimation (MUNE) and MUAP parameters as indicators of clinical muscle dysfunction in patients with amyotrophic lateral sclerosis (ALS), and to analyze the role of MUNE as a supplement to the EMG criteria for the diagnosis of ALS. Methods In 25 patients with ALS, MUNE by the multipoint incremental method in the abductor digiti minimi (ADM) and quantitative EMG in the first dorsal interosseous (FDI) were obtained. The Medical Research Council (MRC) scale was used to evaluate clinical muscle dysfunction. Results A strong correlation between the number of motor units evaluated by MUNE and ADM clinical function by the MRC scale was found ( P 0.001 ). An increased value of surface-detected single motor action potential was associated with a decreased MRC score for ADM ( P 0.1 ). No relation was found between MUAP parameters in FDIand MRC scores. Conclusion and Significance Our data support the value of the MUNE method for the detection of motor unit loss in ALS, and it could be postulated that MUNE studies may be considered complementary tests for ALS in a future revision of ALS criteria.

S68 SFAP to MUAP: Temporal and spatial characteristics of MU

Motor unit action potential (MUAP) represents the summated activity of single fiber action potentials (SFAP) coming from individual muscle fibers those reside in the pick-up territory of recording needle. Calculated features of MUAP give reliable information concerning the architecture of motor unit under investigation but they also depend on the recording site and technique. In this presentation, features of SFAP will be discussed first as a measure of individual muscle fiber conductivity. Then, how MUAP features are changed by moving the needle near to tendon is questioned. Measuring the bioelectrical activity of motor unit across its territory by scanning EMG will be revisited. SFAP represents the moving quadrupole in near field recordings. The faster the quardupole moves, the quicker the phases of SFAP change and lead to shorter “spike duration” in turn. The distribution of “spike duration” shows less central tendency in myopathic muscle, which can be related to increased variability among the muscle fibers. Furthermore, moving the recording site near to tendon exaggerates this conduction difference and leads to more spiky and temporally dispersed MUAP, a finding that is especially detected in simulation studies. Scanning the electrical activity of motor unit from side to side informs the examiner about the motor unit structure. New algorithms and methods were developed for extracting features from scanning EMG signals. The recorded activity of motor unit during voluntary drive changes by the placement of needle electrode. As it changes, it teaches us a lot!

S67 Special phenomena in the motor unit during voluntary and electrical activation

Different information is obtained about the motor unit (MU) from various EMG methods. Single Fiber EMG (SFEMG) explores individual muscle fibers and endplates, conventional EMG a larger part of the MU and Macro EMG represents the entire MU. The presentation will first discuss consequences for routine EMG of the temporal and spatial variation in the activation of MUs that may lead to misinterpretation of some EMG features. It will also highlight some physiological parameters of conduction along a muscle fiber based on SFEMG. The muscle fiber velocity shows a short-term facilitation by previous activity, which gives rise to variation in arrival time to the recording electrode, seen both at voluntary and electrical stimulation. During long term activity on the other hand, the velocity decreases, seen and heard as change in frequency spectrum of the EMG signals. A special phenomenon is the decrease in action potential amplitude in some myotonic disorders. A surface recorded amplitude drop at repetitive stimulation seen in these cases not sign of neuromuscular junction disturbance, but reflects amplitude changes of individual fiber action potentials. Amplitude of single fiber action potentials also varies in relationship to just previous activity, with lower amplitude for short intervals, also seen in conventional EMG. Different types of reflexes involving just one or a few neurons can be studied with SFEMG. Different single cell phenomena can be studied in situ in man, and many of these details can be seen in routine EMG, once we are aware of them.

Simultaneous monitoring of single cell and of micro-organ activity by PEDOT:PSS covered multi-electrode arrays

Continuous and long-term monitoring of cellular and micro-organ activity is required for new insights into physiology and novel technologies such as Organs-on-Chip. Moreover, recent advances in stem cell technology and especially in the field of diabetes call for non-invasive approaches in quality testing of the large quantities of surrogate pancreatic islets to be generated. Electrical activity of such a micro-organ results in single cell action potentials (APs) of high frequency and in low frequency changes in local field potentials (slow potentials or SPs), reflecting coupled cell activity and overall organ physiology. Each of them is indicative of different physiological stages in islet activation. Action potentials in islets are of small amplitude and very difficult to detect. The use of PEDOT:PSS to coat metal electrodes is expected to reduce noise and results in a frequency-dependent change in impedance, as shown here. Whereas detection of high-frequency APs improves, low frequency SPs are less well detected which is, however, an acceptable trade off in view of the strong amplitude of SPs. Using a dedicated software, recorded APs and SPs can be automatically diagnosed and analyzed. Concomitant capture of the two signals will considerably increase the diagnostic power of monitoring islets and islet surrogates in fundamental research as well as drug screening or the use of islets as biosensors.

Time-Resolved Fast Mammalian Behavior Reveals the Complexity of Protective Pain Responses

Potentially harmful stimuli are detected at the skin by nociceptor sensory neurons that drive rapid protective withdrawal reflexes and pain. We set out to define, at a millisecond timescale, the relationship between the activity of these sensory neurons and the resultant behavioral output. Brief optogenetic activation of cutaneous nociceptors was found to activate only a single action potential in each fiber. This minimal input was used to determine high-speed behavioral responses in freely behaving mice. The localized stimulus generated widespread dynamic repositioning and alerting sub-second behaviors whose nature and timing depended on the context of the animal and its position, activity, and alertness. Our findings show that the primary response to injurious stimuli is not limited, fixed, or localized, but is dynamic, and that it involves recruitment and gating of multiple circuits distributed throughout the central nervous system at a sub-second timescale to effectively both alert to the presence of danger and minimize risk of harm.

Differential Contribution of Ca2+-Dependent Mechanisms to Hyperexcitability in Layer V Neurons of the Medial Entorhinal Cortex

Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of GABAA receptor antagonists, stimulation of afferent fibers, terminating both at proximal and distal dendritic locations, initiated hyperexcitable bursts in layer V medial entorhinal neurons. We investigated the differential contribution of Ca2+-dependent mechanisms to the plateaus underlying these bursts at proximal and distal synapses. We found that the NMDA glutamatergic antagonist D,L-2-amino-5-phosphonovaleric acid (APV; 50 μM) reduced both the area and duration of the bursts at both proximal and distal synapses by about half. The L-type Ca2+ channel blocker nimodipine (10 μM) and the R- and T-type Ca2+ channel blocker NiCl2 (200 μM) decreased the area of the bursts to a lesser extent; none of these effects appeared to be location-dependent. Remarkably, the perfusion of flufenamic acid (FFA; 100 μM), to block Ca2+-activated non-selective cation currents (ICAN) mediated by transient receptor potential (TRP) channels, had a location-dependent effect, by abolishing burst firing and switching the suprathreshold response to a single action potential (AP) for proximal stimulation, but only minimally affecting the bursts evoked by distal stimulation. A similar outcome was found when FFA was pressure-applied locally around the proximal dendrite of the recorded neurons and in the presence of a selective blocker of melastatin TRP (TRPM) channels, 9-phenanthrol (100 μM), whereas a selective blocker of canonical TRP (TRPC) channels, SKF 96365, did not affect the bursts. These results indicate that different mechanisms might contribute to the initiation of hyperexcitability in layer V neurons at proximal and distal synapses and could shed light on the initiation of epileptiform activity in the entorhinal cortex.

Fast calcium transients translate the distribution and conduction of neural activity in different regions of a single sensory neuron.

In the present study, cytosolic calcium concentration changes were recorded in response to various forms of excitations, using the fluorescent calcium indicator dye OG-BAPTA1 together with the current or voltage clamp methods in stretch receptor neurons of crayfish. A single action potential evoked a rise in the resting calcium level in the axon and axonal hillock, whereas an impulse train or a large saturating current injection would be required to evoke an equivalent response in the dendrite region. Under voltage clamp conditions, amplitude differences between axon and dendrite responses vanished completely. The fast activation time and the modulation of the response by extracellular calcium concentration changes indicated that the evoked calcium transients might be mediated by calcium entry into the cytosol through a voltage-gated calcium channel. The decay of the responses was slow and sensitive to extracellular sodium and calcium concentrations as well as exposure to 1-10mM NiCl2 and 10-500µM lanthanum. Thus, a sodium calcium exchanger and a calcium ATPase might be responsible for calcium extrusion from the cytosol. Present results indicate that the calcium indicator OG-BAPTA1 might be an efficient but indirect way of monitoring regional membrane potential differences in a single neuron.

Ion Channels of Pituitary Gonadotrophs and Their Roles in Signaling and Secretion.

Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM). These cells also express the hyperpolarization-activated and cyclic nucleotide-gated cation channels at the PM, as well as GABAA, nicotinic, and purinergic P2X channels gated by γ-aminobutyric acid (GABA), acetylcholine (ACh), and ATP, respectively. Activation of these channels leads to initiation or amplification of the pacemaking activity, facilitation of calcium influx, and activation of the exocytic pathway. Gonadotrophs also express calcium-conducting channels at the endoplasmic reticulum membranes gated by inositol trisphosphate and intracellular calcium. These channels are activated potently by hypothalamic gonadotropin-releasing hormone (GnRH) and less potently by several paracrine calcium-mobilizing agonists, including pituitary adenylate cyclase-activating peptides, endothelins, ACh, vasopressin, and oxytocin. Activation of these channels causes oscillatory calcium release and a rapid gonadotropin release, accompanied with a shift from tonic firing of single APs to periodic bursting type of electrical activity, which accounts for a sustained calcium signaling and gonadotropin secretion. This review summarizes our current understanding of ion channels as signaling molecules in gonadotrophs, the role of GnRH and paracrine agonists in their gating, and the cross talk among channels.

Ion channel mechanisms underlying frequency-firing patterns of the avian nucleus magnocellularis: A computational model

ABSTRACTWe have previously shown that late-developing avian nucleus magnocellularis (NM) neurons (embryonic [E] days 19–21) fire action potentials (APs) that resembles a band-pass filter in response to sinusoidal current injections of varying frequencies. NM neurons located in the mid- to high-frequency regions of the nucleus fire preferentially at 75 Hz, but only fire a single onset AP to frequency inputs greater than 200 Hz. Surprisingly, NM neurons do not fire APs to sinusoidal inputs less than 20 Hz regardless of the strength of the current injection. In the present study we evaluated intrinsic mechanisms that prevent AP generation to low frequency inputs. We constructed a computational model to simulate the frequency-firing patterns of NM neurons based on experimental data at both room and near physiologic temperatures. The results from our model confirm that the interaction among low- and high-voltage activated potassium channels (KLVA and KHVA, respectively) and voltage dependent sodium channels (NaV) give rise to the frequency-firing patterns observed in vitro. In particular, we evaluated the regulatory role of KLVA during low frequency sinusoidal stimulation. The model shows that, in response to low frequency stimuli, activation of large KLVA current counterbalances the slow-depolarizing current injection, likely permitting NaV closed-state inactivation and preventing the generation of APs. When the KLVA current density was reduced, the model neuron fired multiple APs per sinusoidal cycle, indicating that KLVA channels regulate low frequency AP firing of NM neurons. This intrinsic property of NM neurons may assist in optimizing response to different rates of synaptic inputs.

Functional imaging of neuronal activity of auditory cortex by using Cal-520 in anesthetized and awake mice.

The organization in the primary auditory cortex (Au1) is critical to the basic function of auditory information processing and integration. However, recent mapping experiments using in vivo two-photon imaging with different Ca2+ indicators have reached controversial conclusions on this topic, possibly because of the different sensitivities and properties of the indicators used. Therefore, it is essential to identify a reliable Ca2+ indicator for use in in vivo functional imaging of the Au1, to understand its functional organization. Here, we demonstrate that a previously reported indicator, Cal-520, performs well in both anesthetized and awake conditions. Cal-520 shows a sufficient sensitivity for the detection of single action potentials, and a high signal-to-noise ratio. Cal-520 reliably reported on both spontaneous and sound-evoked neuronal activity in anesthetized and awake mice. After testing with pure tones at a range of frequencies, we confirmed the local heterogeneity of the functional organization of the mouse Au1. Therefore, Cal-520 is a reliable and useful Ca2+ indicator for in vivo functional imaging of the Au1.

Neuronal excitation and permeabilization by 200-ns pulsed electric field: An optical membrane potential study with FluoVolt dye

Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca2+ signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within <1ms. The OMP recovery started rapidly (τ=8–12ms) but gradually slowed down (to τ>10s), so cells remained above the resting OMP level for at least 20–30s. Activation of voltage-gated sodium channels (VGSC) enhanced the depolarizing effect of electroporation, resulting in an additional tetrodotoxin-sensitive OMP peak in 4–5ms after nsPEF. Omitting Ca2+ in the extracellular solution did not reduce the depolarization, suggesting no contribution of voltage-gated calcium channels (VGCC). In 40% of neurons, nsPEF triggered a single action potential (AP), with the median threshold of 3kV/cm (range: 1.9–4kV/cm); no APs could be evoked by stimuli below the electroporation threshold (1.5–1.9kV/cm). VGSC opening could already be detected in 0.5ms after nsPEF, which is too fast to be mediated by the depolarizing effect of electroporation. The overlap of electroporation and AP thresholds does not necessarily reflect the causal relation, but suggests a low potency of nsPEF, as compared to conventional electrostimulation, for VGSC activation and AP induction.

Label-Free Vibrational Spectroscopic Imaging of Neuronal Membrane Potential.

Detecting membrane potentials is critical for understanding how neuronal networks process information. We report a vibrational spectroscopic signature of neuronal membrane potentials identified through hyperspectral stimulated Raman scattering (SRS) imaging of patched primary neurons. High-speed SRS imaging allowed direct visualization of puff-induced depolarization of multiple neurons in mouse brain slices, confirmed by simultaneous calcium imaging. The observed signature, partially dependent on sodium ion influx, is interpreted as ion interactions on the CH3 Fermi resonance peak in proteins. By implementing a dual-SRS balanced detection scheme, we detected single action potentials in electrically stimulated neurons. These results collectively demonstrate the potential of sensing neuronal activities at multiple sites with a label-free vibrational microscope.

MP26-12 MOTOR UNIT NUMBER ESTIMATION OF THE PUBORECTALIS MUSCLE

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2017MP26-12 MOTOR UNIT NUMBER ESTIMATION OF THE PUBORECTALIS MUSCLE Nicholas Dias, Yun Peng, Jinbao He, Charles Popeney, and Yingchun Zhang Nicholas DiasNicholas Dias More articles by this author , Yun PengYun Peng More articles by this author , Jinbao HeJinbao He More articles by this author , Charles PopeneyCharles Popeney More articles by this author , and Yingchun ZhangYingchun Zhang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.783AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Motor unit number estimation (MUNE) techniques estimate the number of functioning motor units (MUs) in a muscle, and serve as a biomarker for neuromuscular and muscular atrophy. Application of current MUNE techniques to the pelvic floor is impractical because of the need for either multiple stimulations or invasive needle electrodes. The objective is to propose a novel MUNE technique applicable to pelvic floor muscles, by combining a high-density surface EMG (HD-sEMG) decomposition approach with pudendal nerve stimulation, negating the need for invasive needles or multiple stimulations. METHODS All procedures were approved by UH IRB. The pudendal nerve was stimulated transrectally with a St. Mark′s electrode mounted on the operator′s glove. HD-sEMG recordings were acquired from the puborectalis muscle with a vaginal EMG probe (Figure 1b) during supramaximal stimulation and three maximal voluntary contractions of pelvic floor muscles. Firstly, single motor unit action potentials (SMUPs) were decomposed from EMG recordings during muscle contraction using our recently developed K-Means Clustering Convolution Kernel Compensation (KmCKC) Algorithm. All SMUPs were grouped into left or right side by visually checking their innervation zone locations following an established procedure. Next, mean SMUPs were derived for both sides by averaging all HD-sEMG profiles of grouped SMUPs. Last, MUNE was calculated as the weighted average of compound muscle action potential (CMAP) size to mean SMUP size ratios for both sides. RESULTS Left and right branches of the pudendal nerve were simulated. Four SMUPs were decomposed from HD-sEMG signals (left: 3 and right: 1). MUNE for the left and right sides were 22.8 and 27.0, respectively. CONCLUSIONS This pilot study proves the feasibility of a novel MUNE technique for muscles in the pelvic floor region. The KmCKC algorithm enables a non-invasive collection of SMUPs, negating the need for repeated electrical stimulation or invasive needle electrodes. Results from more subjects will be available from our ongoing subject recruitment. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e324 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Nicholas Dias More articles by this author Yun Peng More articles by this author Jinbao He More articles by this author Charles Popeney More articles by this author Yingchun Zhang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Optimizing the design of bipolar nerve cuff electrodes for improved recording of peripheral nerve activity

Objective. Differential measurement of efferent and afferent peripheral nerve activity offers a promising means of improving the clinical utility of implantable neuroprostheses. The tripolar nerve cuff electrode has historically served as the gold standard for achieving high signal-to-noise ratios (SNRs) of the recordings. However, the symmetrical geometry of this electrode array (i.e. electrically-shorted side contacts) precludes it from measuring electrical signals that can be used to obtain directional information. In this study, we investigated the feasibility of using a bipolar nerve cuff electrode to achieve high-SNR of peripheral nerve activity. Approach. A finite element model was implemented to investigate the effects of electrode design parameters—electrode length, electrode edge length (EEL), and a conductive shielding layer (CSL)—on simulated single fiber action potentials (SFAP) and also artifact noise signals (ANS). Main results. Our model revealed that the EEL was particularly effective in increasing the peak-to-peak amplitude of the SFAP (319%) and reducing the common mode ANS (67%) of the bipolar cuff electrode. By adding a CSL to the bipolar cuff electrode, the SNR was found to be 65.2% greater than that of a conventional tripolar cuff electrode. In vivo experiments in anesthetized rats confirmed that a bipolar cuff electrode can achieve a SNR that is 38% greater than that achieved by a conventional tripolar cuff electrode (p < 0.05). Significance. The current study showed that bipolar nerve cuff electrodes can be designed to achieve SNR levels that are comparable to that of tripolar configuration. Further work is needed to confirm that these bipolar design parameters can be used to record bi-directional neural activity in a physiological setting.

Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex.