Mean Spike Research Articles

The effect of serotonin on penicillin-induced epileptiform activity

Objective: This study was aimed at examining the epileptiform activity of the 5-HT2 serotonin receptor agonist and antagonist, and 5-hydroxytryptophan (5-HTP) in penicillin-induced epilepsy in albino Wistar rats.Methods: For this purpose, 90 albino male Wistar rats were used in this study. Epileptiform activity was induced by an injection of penicillin, an agonist of GABAA receptor, (500 IU, i.c.) into the somatomotor cortex. Thirty minutes after the injection of penicillin, 2,5-dimethoxy-4-iodoamphetamine (DOI, an agonist of 5-HT2 receptor) (0.5, 1, 2 and 4 mg/kg, i.p.), methysergide, an antagonist of 5-HT2 receptor, (1, 10, 20, 50 and 100 µM, i.c.v.) and 5-HTP, precursor of 5-HT, (25, 50, 75 and 100 mg/kg, i.p.) were administered, respectively.Results: DOI, at the doses of 1 and 2 mg/kg, significantly decreased penicillin-induced epileptiform activity (p < 0.05). Methysergide, at the doses of 20, 50 and 100 µM, significantly increased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The doses of 50, 75 and 100 mg/kg of 5-HTP decreased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The mean of amplitude of penicillin-induced epileptiform activity did not significantly change in any of the groups (p > 0.05).Conclusion: The electrophysiological data from the present study suggest that serotonin 5-HT2 receptors have an important role in controlling penicillin-induced epileptiform activity in the rat.

Intracochlear near infrared stimulation: Feasibility of optoacoustic stimulation in vivo

Intracochlear optical stimulation has been suggested as an alternative approach to hearing prosthetics in recent years. This study investigated the properties of a near infrared laser (NIR) induced optoacoustic effect. Pressure recordings were performed at the external meatus of anaesthetized guinea pigs during intracochlear NIR stimulation. The sound pressure and power spectra were determined. The results were compared to multi unit responses in the inferior colliculus (IC). Additionally, the responses to NIR stimulation were compared to IC responses induced by intracochlear electric stimulation at the same cochlear position to investigate a potentially confounding contribution of direct neural NIR stimulation. The power spectra of the sound recorded at the external meatus (n = 7) had most power at frequencies below 10 kHz and showed little variation for different stimulation sites. The mean spike rates of IC units responding to intracochlear NIR stimulation (n = 222) of 17 animals were significantly correlated with the power of the externally recorded signal at frequencies corresponding to the best frequencies of the IC units. The response strength as well as the sound pressure at the external meatus depended on the pulse peak power of the optical stimulus. The sound pressure recorded at the external meatus reached levels above 70 dB SPL peak equivalent. In hearing animals a cochlear activation apical to the location of the fiber was found. The absence of any NIR responses after pharmacologically deafening and the comparison to electric stimulation at the NIR stimulation site revealed no indication of a confounding direct neural NIR stimulation. Intracochlear optoacoustic stimulation might become useful in combined electro-acoustic stimulation devices in the future.

A novel mutual information estimator to measure spike train correlations in a model thalamocortical network.

The impact of thalamic state on information transmission to the cortex remains poorly understood. This limitation exists due to the rich dynamics displayed by thalamocortical networks and because of inadequate tools to characterize those dynamics. Here, we introduce a novel estimator of mutual information and use it to determine the impact of a computational model of thalamic state on information transmission. Using several criteria, this novel estimator, which uses an adaptive partition, is shown to be superior to other mutual information estimators with uniform partitions when used to analyze simulated spike train data with different mean spike rates, as well as electrophysiological data from simultaneously recorded neurons. When applied to a thalamocortical model, the estimator revealed that thalamocortical cell T-type calcium current conductance influences mutual information between the input and output from this network. In particular, a T-type calcium current conductance of ~40 nS appears to produce maximal mutual information between the input to this network (conceptualized as afferent input to the thalamocortical cell) and the output of the network at the level of a layer 4 cortical neuron. Furthermore, at particular combinations of inputs to thalamocortical and thalamic reticular nucleus cells, thalamic cell bursting correlated strongly with recovery of mutual information between thalamic afferents and layer 4 neurons. These studies suggest that the novel mutual information estimator has advantages over previous estimators and that thalamic reticular nucleus activity can enhance mutual information between thalamic afferents and thalamorecipient cells in the cortex. NEW & NOTEWORTHY In this study, a novel mutual information estimator was developed to analyze information flow in a model thalamocortical network. Our findings suggest that this estimator is a suitable tool for signal transmission analysis, particularly in neural circuits with disparate firing rates, and that the thalamic reticular nucleus can potentiate ascending sensory signals, while thalamic recipient cells in the cortex can recover mutual information in ascending sensory signals that is lost due to thalamic bursting.

The effects of TGN-020 on penicillin induced epileptiform activity in rats

Objective: Aquaporin-4 (AQP-4) is a water channel protein which is the most abundant aquaporin isoform in the brain. Recent studies indicate the relationship between AQP-4 with epileptogenesis . Therefore, w e examined the potential effect of the AQP-4 inhibitor TGN-020 on penicillin-induced epileptiform activity in rats. Material and Method: Epileptiform activity was induced by intracortical (i.c.) administration of penicillin (200 IU, 1 μl). TGN-020, at doses of 25 µg, 50 µg, 100 µg and 200 µg, was administered by intracerebroventricular (i.c.v.) 30 minutes after penicillin injection. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. Twenty four hours later, animals are decapitated for the collection of blood samples and brain tissue. Results: The dose of 100 µg TGN-020 decreased the mean spike frequency of epileptiform activity in the 30 min after the injection without changing the amplitude (p < 0.05). Serum neuropeptide Y level was up-regulated by 25 µg TGN-020 in comparison with the other groups (p<0.001). Plasma levels of calcineurin in the 50 µ g dose of TGN-020 were lower than 25 µg and 200 µg doses of TGN-020 ( p<0.01) . E nzymatic ativity of glutathione peroxidase (GP x -1) in brain tissue was higher in the penicillin and 25 µg TGN-020 group compared with the sham group (p < 0.05). Conclusion: Given all these data, the anticonvulsant effect of TGN-020 which is aquaporin-4 water channel inhibitor in the brain has been studied extensively for the first time in an experimental model of epilepsy. Inhibition of AQP-4 might be useful in the treatment of epilepsy in future.

Phase-sensitive excitability of a limit cycle

The classical notion of excitability refers to an equilibrium state that shows under the influence of perturbations a nonlinear threshold-like behavior. Here, we extend this concept by demonstrating how periodic orbits can exhibit a specific form of excitable behavior where the nonlinear threshold-like response appears only after perturbations applied within a certain part of the periodic orbit, i.e., the excitability happens to be phase-sensitive. As a paradigmatic example of this concept, we employ the classical FitzHugh-Nagumo system. The relaxation oscillations, appearing in the oscillatory regime of this system, turn out to exhibit a phase-sensitive nonlinear threshold-like response to perturbations, which can be explained by the nonlinear behavior in the vicinity of the canard trajectory. Triggering the phase-sensitive excitability of the relaxation oscillations by noise, we find a characteristic non-monotone dependence of the mean spiking rate of the relaxation oscillation on the noise level. We explain this non-monotone dependence as a result of an interplay of two competing effects of the increasing noise: the growing efficiency of the excitation and the degradation of the nonlinear response.

Human iPSC-derived neuronal models for in vitro neurotoxicity assessment

Neurotoxicity testing still relies on ethically debated, expensive and time consuming in vivo experiments, which are unsuitable for high-throughput toxicity screening. There is thus a clear need for a rapid in vitro screening strategy that is preferably based on human-derived neurons to circumvent interspecies translation. Recent availability of commercially obtainable human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes holds great promise in assisting the transition from the current standard of rat primary cortical cultures to an animal-free alternative.We therefore composed several hiPSC-derived neuronal models with different ratios of excitatory and inhibitory neurons in the presence or absence of astrocytes. Using immunofluorescent stainings and multi-well micro-electrode array (mwMEA) recordings we demonstrate that these models form functional neuronal networks that become spontaneously active. The differences in development of spontaneous neuronal activity and bursting behavior as well as spiking patterns between our models confirm the importance of the presence of astrocytes. Preliminary neurotoxicity assessment demonstrates that these cultures can be modulated with known seizurogenic compounds, such as picrotoxin (PTX) and endosulfan, and the neurotoxicant methylmercury (MeHg). However, the chemical-induced effects on different parameters for neuronal activity, such as mean spike rate (MSR) and mean burst rate (MBR), may depend on the ratio of inhibitory and excitatory neurons. Our results thus indicate that hiPSC-derived neuronal models must be carefully designed and characterized prior to large-scale use in neurotoxicity screening.

All-Optical Electrophysiology for High-Throughput Functional Characterization of a Human iPSC-Derived Motor Neuron Model of ALS.

SummaryHuman induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, “Optopatch,” pipeline for high-throughput functional characterization of human iPSC-derived neuronal cultures. We demonstrate the method in a human iPSC-derived motor neuron (iPSC-MN) model of amyotrophic lateral sclerosis (ALS). In a comparison of iPSC-MNs with an ALS-causing mutation (SOD1 A4V) with their genome-corrected controls, the mutants showed elevated spike rates under weak or no stimulus and greater likelihood of entering depolarization block under strong optogenetic stimulus. We compared these results with numerical simulations of simple conductance-based neuronal models and with literature results in this and other iPSC-based models of ALS. Our data and simulations suggest that deficits in slowly activating potassium channels may underlie the changes in electrophysiology in the SOD1 A4V mutation.

Overexpression of cypin alters dendrite morphology, single neuron activity, and network properties via distinct mechanisms

Objective. This study investigates the effect that overexpression of cytosolic PSD-95 interactor (cypin), a regulator of synaptic PSD-95 protein localization and a core regulator of dendrite branching, exerts on the electrical activity of rat hippocampal neurons and networks. Approach. We cultured rat hippocampal neurons and used lipid-mediated transfection and lentiviral gene transfer to achieve high levels of cypin or cypin mutant (cypinΔPDZ; PSD-95 non-binding) expression cellularly and network-wide, respectively. Main results. Our analysis revealed that although overexpression of cypin and cypinΔPDZ increase dendrite numbers and decrease spine density, cypin and cypinΔPDZ distinctly regulate neuronal activity. At the single cell level, cypin promotes decreases in bursting activity while cypinΔPDZ reduces sEPSC frequency and further decreases bursting compared to cypin. At the network level, by using the Fano factor as a measure of spike count variability, cypin overexpression results in an increase in variability of spike count, and this effect is abolished when cypin cannot bind PSD-95. This variability is also dependent on baseline activity levels and on mean spike rate over time. Finally, our spike sorting data show that overexpression of cypin results in a more complex distribution of spike waveforms and that binding to PSD-95 is essential for this complexity. Significance. Our data suggest that dendrite morphology does not play a major role in cypin action on electrical activity.

Effect of a novel TRPV1 antagonist on capsaicin nociceptors

Effect of a novel TRPV1 antagonist on capsaicin nociceptors

Differential cholinergic and serotonergic neuromodulation of network activity in the mouse medial prefrontal cortex

Differential cholinergic and serotonergic neuromodulation of network activity in the mouse medial prefrontal cortex

Synchrony changes on different time-scales during in vitro neuronal network development

Synchrony changes on different time-scales during in vitro neuronal network development

In vivo characterization of the electrophysiological and astrocytic responses to a silicon neuroprobe implanted in the mouse neocortex

Silicon neuroprobes hold great potential for studies of large-scale neural activity and brain computer interfaces, but data on brain response in chronic implants is limited. Here we explored with in vivo cellular imaging the response to multisite silicon probes for neural recordings. We tested a chronic implant for mice consisting of a CMOS-compatible silicon probe rigidly implanted in the cortex under a cranial imaging window. Multiunit recordings of cortical neurons with the implant showed no degradation of electrophysiological signals weeks after implantation (mean spike and noise amplitudes of 186 ± 42 µVpp and 16 ± 3.2 µVrms, respectively, n = 5 mice). Two-photon imaging through the cranial window allowed longitudinal monitoring of fluorescently-labeled astrocytes from the second week post implantation for 8 weeks (n = 3 mice). The imaging showed a local increase in astrocyte-related fluorescence that remained stable from the second to the tenth week post implantation. These results demonstrate that, in a standard electrophysiology protocol in mice, rigidly implanted silicon probes can provide good short to medium term chronic recording performance with a limited astrocyte inflammatory response. The precise factors influencing the response to silicon probe implants remain to be elucidated.

Spike Timing Matters in Novel Neuronal Code Involved in Vibrotactile Frequency Perception

Skin vibrations sensed by tactile receptors contribute significantly to the perception of object properties during tactile exploration [1-4] and to sensorimotor control during object manipulation [5]. Sustained low-frequency skin vibration (<60Hz) evokes a distinct tactile sensation referred to as flutter whose frequency can be clearly perceived [6]. How afferent spiking activity translates into the perception of frequency is still unknown. Measures based on mean spike rates of neurons in the primary somatosensory cortex are sufficient to explain performance in some frequency discrimination tasks [7-11]; however, thereis emerging evidence that stimuli can be distinguished based also on temporal features of neural activity [12, 13]. Our study's advance is to demonstrate that temporal features are fundamental for vibrotactile frequency perception. Pulsatile mechanical stimuli were used to elicit specified temporal spike train patterns in tactile afferents, and subsequently psychophysical methods were employed to characterize human frequency perception. Remarkably, the most salient temporal feature determining vibrotactile frequency was not the underlying periodicity but, rather, the duration of the silent gap between successive bursts of neural activity. This burst gap code for frequency represents a previously unknown form ofneural coding in the tactile sensory system, whichparallels auditory pitch perception mechanisms based on purely temporal information where longer inter-pulse intervals receive higher perceptual weights than short intervals [14]. Our study also demonstrates that human perception of stimuli can be determined exclusively by temporal features of spike trains independent of the mean spike rate and without contribution from population response factors.

Magnetoencephalography with temporal spread imaging to visualize propagation of epileptic activity.

We describe temporal spread imaging (TSI) that can identify the spatiotemporal pattern of epileptic activity using Magnetoencephalography (MEG). A three-dimensional grid of voxels covering the brain is created. The array-gain minimum-variance spatial filter is applied to an interictal spike to estimate the magnitude of the source and the time (Ta) when the magnitude exceeds a predefined threshold at each voxel. This calculation is performed through all spikes. Each voxel has the mean Ta (<Ta>) and spike number (Nsp), which is the number of spikes whose source exceeds the threshold. Then, a random resampling method is used to determine the cutoff value of Nsp for the statistically reproducible pattern of the activity. Finally, all the voxels where the source exceeds the threshold reproducibly shown on the MRI with a color scale representing <Ta>. Four patients with intractable mesial temporal lobe epilepsy (MTLE) were analyzed. In three patients, the common pattern of the overlap between the propagation and the hypometabolism shown by fluorodeoxyglucose-positron emission tomography (FDG-PET) was identified. TSI can visualize statistically reproducible patterns of the temporal and spatial spread of epileptic activity. TSI can assess the statistical significance of the spatiotemporal pattern based on its reproducibility.

Acute effects of aceclofenac, COX-2 inhibitor, on penicillin-induced epileptiform activity.

The effects of COX-2 inhibitors on seizure activity are controversial. The aim of the current study was to determine the post-treatment effect of aceclofenac on penicillin-induced experimental epilepsy. Male Wistar rats were used in all experiments (n=18). The seizure activity was triggered by penicillin (i.c.). Aceclofenac was injected intraperitoneally at doses of 10mg/kg and 20mg/kg. Intraperitoneal administration of 10 and 20mg/kg aceclofenac doses, exhibited proconvulsant properties on seizure activity on rats. The mean spike frequency and amplitude of aceclofenac 10mg/kg were 41.89±2.12 spike/min and 0.619±0.094mV, respectively. The mean spike frequency and amplitude of aceclofenac 20mg/kg were 35.26±2.72 spike/min and 0.843±0.089mV, respectively. The results indicated that not all of the COX-2 inhibitors may have anticonvulsant or proconvulsant features on patients with epilepsy susceptibility and must be used with great care. It was also suggested that not only cyclooxygenase metabolic pathway but also lipoxygenase pathway should be considered together in further detailed studies.

Instability Resistance Training Improves Neuromuscular Outcome in Parkinson's Disease.

This study compared the effects of resistance training (RT) and RT with instability (RTI) on neuromuscular and total training volume (TTV) outcomes obtained as part of the Instability Resistance Training Trial in Parkinson's disease. It also used a linear multiple regression (forward stepwise method) to identify the contribution of neuromuscular outcomes to previously published improvements in the timed-up-and-go test and the Unified Parkinson's Disease Rating Scale, motor subscale score. Thirty-nine patients with moderate to severe Parkinson's disease were randomly assigned to three groups: control (C), RT, and RTI. RT and RTI groups performed resistance exercises twice a week for 12 wk, and only the RTI group used unstable devices to perform resistance exercises. The following neuromuscular outcomes were assessed: quadriceps muscle cross-sectional area, root mean square and mean spike frequency of electromyographic signal, peak torque, rate of torque development, and half relaxation time of the knee extensors and plantarflexors during maximum ballistic voluntary isometric contractions. TTV was calculated for lower limb exercises. From pre- to posttraining, RTI improved all of the neuromuscular outcomes (P < 0.05) except half relaxation time of the knee extensors (P = 0.068), despite the lower TTV than RT (P < 0.05). RTI was more effective than RT in increasing the root mean square values of vastus medialis, mean spike frequency of gastrocnemius medialis, and rate of torque development of plantarflexors (P < 0.05). Stepwise regression identified the changes in mean spike frequency of gastrocnemius medialis as the best predictor of improvements in timed-up-and-go test (R = 0.58, P = 0.002) and on-medication Unified Parkinson's Disease Rating Scale, motor subscale scores (R = 0.40, P = 0.020). RTI optimizes neuromuscular adaptations, which partially explains mobility and motor sign improvements in patients with Parkinson's disease.

Validation of the Intrinsic Hepcidin IDxTM Test, an LDT for Clinical Hepcidin Assessment

▪Introduction: Hepcidin is the principal regulator of iron absorption and iron recycling, and is required to provide iron for erythropoiesis. Hepcidin is a peptide hormone that binds to the sole iron channel ferroportin (Fpn), and blocks iron efflux by degrading Fpn, trapping iron stored in the cell. Dysregulation of hepcidin by genetic mutations affecting hepcidin expression in hepatocytes is responsible for hereditary hemochromatosis where too little hepcidin leads to iron-overload disease, and iron refractory iron deficiency anemia (IRIDA) where hepcidin expression is inappropriately high leading to anemia. Hepcidin itself is regulated by iron and the inflammatory cytokine IL-6. Thus, hepcidin is dysregulated in most inflammatory diseases and chronic infections. Interest in developing diagnostic applications for hepcidin in iron disorders is high.Objective: We developed a high-affinity monoclonal antibody (mAb) to hepcidin and used it to produce a competitive ELISA (C-ELISA) similar to our first RUO test (Ganz et al. 2008). We determined the performance characteristics using CLIA analytical method validation guidelines. The Intrinsic Hepcidin IDx Test is used for serum and Li-Heparin plasma. We determined the reference range in adult first time blood donors (n=292) and studied an iron deficient (ID) sub-set of the donors.Methods: We developed mouse anti-human hepcidin monoclonal antibodies and coated, blocked, and dried the plates in a temperature and humidity controlled incubator. We used highly purified synthetic hepcidin as reference standard and a biotinylated hepcidin analog as the competitive tracer for the C-ELISA (Peptides International, Louisville, KY). The Intrinsic Hepcidin IDx Test is fully automated on the Biomek FX platform. Serum from first time blood donors (n=292) was obtained, and ferritin, transferrin, plasma iron, CRP, and hepcidin were measured. The reference range for hepcidin was determined and the normal iron status range determined by eliminating iron deficient (ID) donors or those shown to be iron overloaded. Receiver operator characteristic curves (ROC) were plotted to determine the utility of hepcidin and to identify optimal cutoffs of hepcidin as a test of iron deficiency.Results: The mAb used in the Intrinsic Hepcidin IDx Test is specific for human hepcidin. The analytical measurement range (AMR) is 4 - 200 ng/ml. The intra-assay precision CVs range between 7% (at 12 ng/ml) and 4% (at 99 ng/ml). The between-day precision CVs range between 7% (12 ng/ml) and 9% (100 ng/ml). The mean spike recovery across the AMR is 3%. Hepcidin was stable at 4oC for up to 7 days and if specimens are stored at -20oC, for at least 6 months. Hepcidin concentrations determined in blood donors were highly correlated with those measured using our polyclonal RUO C-ELISA (r = 0.95, p<0.001). The reference range is 4.4-54.1 ng/ml for women and 6.1-91.2 ng/ml for men. Clear gender differences were observed: hepcidin was higher in men (median 28.5 ng/ml, n = 143) than in women (median 13.1 ng/ml, n = 149). In addition, the ID group had lower hepcidin (median 6.7 ng/ml) than the normal iron status group (median 21.4 ng/ml, p<0.0001). The area under the ROC curve for hepcidin compared with various ferritin concentrations was greater than 0.90. An optimal hepcidin cutoff less than 10 ng/ml was determined to predict ID with a correct classification rate of greater than 86%.Conclusion: We developed and validated a sensitive, accurate and reproducible C-ELISA, the Intrinsic Hepcidin IDx test, using CLIA validation guidelines. We determined the hepcidin reference ranges by analyzing first-time blood donor serum. We found a significant difference in median hepcidin values between genders. Also, our data show that hepcidin was lower in donors with ID compared to iron replete, healthy donors. DisclosuresGutschow:Intrinsic LifeSciences: Employment, Equity Ownership. Westerman:Intrinsic LifeSciences: Employment. Han:Intrinsic Lifesciences.: Employment, Equity Ownership. Ostland:Intrinsic LifeScienc s: Employment, Equity Ownership. Olbina:Intrinsic LifeSciences: Employment, Equity Ownership. Westerman:Intrinsic LifeSciences: Employment, Equity Ownership.

Chronic 14-day exposure to insecticides or methylmercury modulates neuronal activity in primary rat cortical cultures

There is an increasing demand for in vitro test systems to detect neurotoxicity for use in chemical risk assessment. In this study, we evaluated the applicability of rat primary cortical cultures grown on multi-well micro-electrode arrays (mwMEAs) to detect effects of chronic 14-day exposure to structurally different insecticides or methylmercury on neuronal activity (mean spike rate; MSR).Effects of chronic exposure to α-cypermethrin, endosulfan, carbaryl, chlorpyrifos(-oxon), methylmercury or solvent control [14days exposure, initiated after baseline recording at day in vitro (DIV)7] were studied in five successive recordings between DIV10 and DIV21. The results were compared to effects of acute exposure to these same compounds (activity recorded immediately after the start of exposure after baseline recording at DIV10-11).Chronic 14-day exposure to methylmercury, chlorpyrifos and α-cypermethrin inhibited MSR, all with a lowest-observed effect concentration (LOEC) of 0.1μM, while exposure to endosulfan increased MSR [LOEC: 1μM]. No significant effects were observed for chlorpyrifos-oxon and carbaryl. Similar to the observations in the chronic 14-day exposure studies, MSR was inhibited by acute 30-min exposure to methylmercury, chlorpyrifos, and α-cypermethrin [LOECs: 1μM, 10μM, and 1μM, respectively], whereas endosulfan increased MSR [LOEC: 0.3μM]. While not observed in the chronic 14-day exposure study, acute exposure to chlorpyrifos-oxon and carbaryl resulted in inhibition of MSR [LOECs: 10μM, and100 μM, respectively]. Effects on median interspike intervals (mISI; a measure for neuronal firing pattern) were not detected following chronic 14-day or acute 30-min exposure, except for increased mISI at acute chlorpyrifos and α-cypermethrin exposures at concentrations that also inhibited MSR.These data indicate that the effects of chronic 14-day exposures to methylmercury and insecticides at low concentrations on spontaneous neuronal activity in vitro can be predicted in rapid acute screening studies using mwMEAs.

Visual Stimulus Detection Correlates with the Consistency of Temporal Sequences within Stereotyped Events of V1 Neuronal Population Activity.

Sensory information about the world is translated into rate codes, such that modulations in mean spiking activity of neurons relate to differences in stimulus features. More recently, it has been proposed that also temporal properties of activity, such as assembly formation and sequential population activation, are important for understanding the relation between neuronal activity and behavioral output. These phenomena appear to be robust properties of neural circuits, but their relevance for perceptual judgments, such as the behavioral detection of stimuli, remains to be tested. Studying neuronal activity with two-photon calcium imaging in primary visual cortex of mice performing a go/no-go visual detection task, we found that assemblies (i.e., configurations of neuronal group activity) reliably recur, as defined using Ward-method clustering. However, population activation events with a recurring configuration of core neurons did not appear to serve a particular function in the coding of orientation or the detection of stimuli. Instead, we found that, regardless of whether the population event showed a recurring or nonrecurring configuration of neurons, the sequence of cluster activation was correlated with the detection of stimuli. Moreover, each neuron showed a preferred temporal position of activation within population events, which was robust despite varying neuronal participation. Furthermore, the timing of neuronal activity within such a sequence was more consistent when a stimulus was detected (hits) than when it remained unreported (misses). Our data indicate that neural processing of information related to visual detection behavior depends on the temporal positioning of individual and group-wise cell activity. Temporally coactive neurons have been hypothesized to form functional assemblies that might subserve different functions in the brain, but many of these proposed functions have not yet been experimentally tested. We used two-photon calcium imaging in V1 of mice performing a stimulus detection task to study the relation of assembly activity to the behavioral detection of visual stimuli. We found that the presence of recurring assemblies per se was not correlated with behavior, and these assemblies did not appear to serve a function in the coding of stimulus orientation. Instead, we found that activity in V1 is characterized by population events of varying membership, within which the consistency of the temporal sequence of neuronal activation is correlated with stimulus detection.

Quantitating Changes in Jitter and Spike Number Using Concentric Needle Electrodes in Amyotrophic Lateral Sclerosis Patients.

Background:Single-fiber electromyography (SFEMG) has been suggested as a quantitative method for supporting chronic partial denervation in amyotrophic lateral sclerosis (ALS) by the revised EI Escorial criteria. Although concentric needle (CN) electrodes have been used to assess jitter in myasthenia gravis patients and healthy controls, there are few reports using CN electrodes to assess motor unit instability and denervation in neurogenic diseases. The aim of this study was to determine whether quantitative changes in jitter and spike number using CN electrodes could be used for ALS studies.Methods:Twenty-seven healthy controls and 23 ALS patients were studied using both CN and single-fiber needle (SFN) electrodes on the extensor digitorum communis muscle with an SFEMG program. The SFN-jitter and SFN-fiber density data were measured using SFN electrodes. The CN-jitter and spike number were measured using CN electrodes.Results:The mean CN-jitter was significantly increased in ALS patients (47.3 ± 17.0 μs) than in healthy controls (27.4 ± 3.3 μs) (P < 0.001). Besides, the mean spike number was significantly increased in ALS patients (2.5 ± 0.5) than in healthy controls (1.7 ± 0.3) (P < 0.001). The sensitivity and specificity in the diagnosis of ALS were 82.6% and 92.6% for CN-jitter (cut-off value: 32 μs), and 91.3% and 96.3% for the spike number (cut-off value: 2.0), respectively. There was no significant difference between the SFN-jitter and CN-jitter in ALS patients; meanwhile, there was no significant difference between the SFN-jitter and CN-jitter in healthy controls.Conclusion:CN-jitter and spike number could be used to quantitatively evaluate changes due to denervation-reinnervation in ALS.