Extracellular Microelectrode Recordings Research Articles

Spiking Laguerre Volterra networks—predicting neuronal activity from local field potentials

Objective. Understanding the generative mechanism between local field potentials (LFP) and neuronal spiking activity is a crucial step for understanding information processing in the brain. Up to now, most approaches have relied on simply quantifying the coupling between LFP and spikes. However, very few have managed to predict the exact timing of spike occurrence based on LFP variations. Approach. Here, we fill this gap by proposing novel spiking Laguerre–Volterra network (sLVN) models to describe the dynamic LFP-spike relationship. Compared to conventional artificial neural networks, the sLVNs are interpretable models that provide explainable features of the underlying dynamics. Main results. The proposed networks were applied on extracellular microelectrode recordings of Parkinson’s Disease patients during deep brain stimulation (DBS) surgery. Based on the predictability of the LFP-spike pairs, we detected three neuronal populations with unique signal characteristics and sLVN model features. Significance. These clusters were indirectly associated with motor score improvement following DBS surgery, warranting further investigation into the potential of spiking activity predictability as an intraoperative biomarker for optimal DBS lead placement.

Multiformity of extracellular microelectrode recordings from Aδ neurons in the dorsal root ganglia: a computational modeling study.

Microelectrodes serve as a fundamental tool in electrophysiology research throughout the nervous system, providing a means of exploring neural function with a high resolution of neural firing information. We constructed a hybrid computational model using the finite element method and multicompartment cable models to explore factors that contribute to extracellular voltage waveforms that are produced by sensory pseudounipolar neurons, specifically smaller A-type neurons, and that are recorded by microelectrodes in dorsal root ganglia. The finite element method model included a dorsal root ganglion, surrounding tissues, and a planar microelectrode array. We built a multicompartment neuron model with multiple trajectories of the glomerular initial segment found in many A-type sensory neurons. Our model replicated both the somatic intracellular voltage profile of Aδ low-threshold mechanoreceptor neurons and the unique extracellular voltage waveform shapes that are observed in experimental settings. Results from this model indicated that tortuous glomerular initial segment geometries can introduce distinct multiphasic properties into a neuron's recorded waveform. Our model also demonstrated how recording location relative to specific microanatomical components of these neurons, and recording distance from these components, can contribute to additional changes in the multiphasic characteristics and peak-to-peak voltage amplitude of the waveform. This knowledge may provide context for research employing microelectrode recordings of pseudounipolar neurons in sensory ganglia, including functional mapping and closed-loop neuromodulation. Furthermore, our simulations gave insight into the neurophysiology of pseudounipolar neurons by demonstrating how the glomerular initial segment aids in increasing the resistance of the stem axon and mitigating rebounding somatic action potentials.NEW & NOTEWORTHY We built a computational model of sensory neurons in the dorsal root ganglia to investigate factors that influence the extracellular waveforms recorded by microelectrodes. Our model demonstrates how the unique structure of these neurons can lead to diverse and often multiphasic waveform profiles depending on the location of the recording contact relative to microanatomical neural components. Our model also provides insight into the neurophysiological function of axon glomeruli that are often present in these neurons.

The Mechanism of α2 adrenoreceptor-dependent Modulation of Neurotransmitter Release at the Neuromuscular Junctions.

α2-Adrenoreceptors (ARs) are main Gi-protein coupled autoreceptors in sympathetic nerve terminals and targets for dexmedetomidine (DEX), a widely used sedative. We hypothesize that α2-ARs are also potent regulators of neuromuscular transmission via G protein-gated inwardly rectifying potassium (GIRK) channels. Using extracellular microelectrode recording of postsynaptic potentials, we found DEX-induced inhibition of spontaneous and evoked neurotransmitter release as well as desynchronization of evoked exocytotic events in the mouse diaphragm neuromuscular junction. These effects were suppressed by SKF-86,466, a selective α2-AR antagonist. An activator of GIRK channels ML297 had the same effects on neurotransmitter release as DEX. By contrast, inhibition of GIRK channels with tertiapin-Q prevented the action of DEX on evoked neurotransmitter release, but not on spontaneous exocytosis. The synaptic vesicle exocytosis is strongly dependent on Ca2+ influx through voltage-gated Ca2+ channels (VGCCs), which can be negatively regulated via α2-AR - GIRK channel axis. Indeed, inhibition of P/Q-, L-, N- or R-type VGCCs prevented the inhibitory action of DEX on evoked neurotransmitter release; antagonists of P/Q- and N-type channels also suppressed the DEX-mediated desynchronization of evoked exocytotic events. Furthermore, inhibition of P/Q-, L- or N-type VGCCs precluded the frequency decrease of spontaneous exocytosis upon DEX application. Thus, α2-ARs acting via GIRK channels and VGCCs (mainly, P/Q- and N-types) exert inhibitory effect on the neuromuscular communication by attenuating and desynchronizing evoked exocytosis. In addition, α2-ARs can suppress spontaneous exocytosis through GIRK channel-independent, but VGCC-dependent pathway.

Metrics of high cofluctuation and entropy to describe control of cardiac function in the stellate ganglion.

Stellate ganglia within the intrathoracic cardiac control system receive and integrate central, peripheral, and cardiopulmonary information to produce postganglionic cardiac sympathetic inputs. Pathological anatomical and structural remodeling occurs within the neurons of the stellate ganglion (SG) in the setting of heart failure (HF). A large proportion of SG neurons function as interneurons whose networking capabilities are largely unknown. Current therapies are limited to targeting sympathetic activity at the cardiac level or surgical interventions such as stellectomy, to treat HF. Future therapies that target the SG will require understanding of their networking capabilities to modify any pathological remodeling. We observe SG networking by examining cofluctuation and specificity of SG networked activity to cardiac cycle phases. We investigate network processing of cardiopulmonary transduction by SG neuronal populations in porcine with chronic pacing-induced HF and control subjects during extended in-vivo extracellular microelectrode recordings. We find that information processing and cardiac control in chronic HF by the SG, relative to controls, exhibits: (i) more frequent, short-lived, high magnitude cofluctuations, (ii) greater variation in neural specificity to cardiac cycles, and (iii) neural network activity and cardiac control linkage that depends on disease state and cofluctuation magnitude.

Impaired visceral pain-related functions of the midbrain periaqueductal gray in rats with colitis

The midbrain periaqueductal gray (PAG) is a key structure involved in the supraspinal modulation of pain. Previous studies have reported the association of gut inflammation-triggered chronic abdominal pain with structural and neuronal alterations within the PAG. However, whether PAG-executed visceral nociception processing and descending modulation are altered in gut pathology is not known. We used c-Fos immunohistochemistry and extracellular microelectrode recording in urethane-anesthetized male Wistar rats to evaluate the colitis-induced changes in visceral pain-related neuronal properties of the PAG and its descending outflow to visceral nociceptive neurons of the caudal ventrolateral medulla (CVLM). Analysis of c-Fos protein expression in inflamed animals has shown diminished activation of the lateral and ventrolateral PAG columns by noxious colorectal distension (CRD), although the nonstimulated c-Fos labeling in these PAG subdivisions was enhanced compared with that in controls. Microelectrode recording in the ventrolateral PAG revealed a colitis-elicited decrease in the proportion of CRD-excited neurons accompanied by an increase in the number of unresponsive cells and weakened reactions to the stimulation of CRD-inhibited PAG units. Colonic inflammation has also been found to cause a shift in the effects of ventrolateral PAG electrostimulation on CRD-excited CVLM neurons from being mostly inhibitory under normal conditions to excitatory in colitis. These findings identify impaired PAG functioning in ascending and descending visceral nociception control that may contribute to gut injury-associated visceral hyperalgesia. The data obtained can benefit a better understanding of the supraspinal mechanisms involved in the pathogenesis of postinflammatory chronic abdominal pain.

5‐HT1A Receptor Activation by Buspirone Facilitates Post‐Inflammatory Intestinal Hypersensitivity in a Rat Model

Intestinal hypersensitivity is the most common symptom and cause of pain in patients with post-inflammatory irritable bowel syndrome (PI-IBS). Several lines of evidence suggest that central serotonin (5-HT) and its receptors significantly contribute to the phenomenon and therefore may be prospective therapeutic targets for relieving abdominal pain and discomfort in PI-IBS. We demonstrated previously that buspirone, a partial agonist of the 5-HT1A receptors, dose-dependently inhibited visceromotor reactions and medullary neuronal responses to noxious colorectal distension in healthy awake dogs and anesthetized rats, indicating the drug's antinociceptive properties in normal conditions. However, whether the 5-HT1A agonist can be beneficial for post-inflammatory intestinal hypersensitivity and hyperalgesia, which are thought to be associated with altered central 5-HT signaling, is still unknown. In the presented study, the effect of systemic buspirone (Sigma-Aldrich, USA) on intestinal hypersensitivity and its underlying neuronal mechanisms were evaluated in Wistar rats recovered from trinitrobenzene sulfonic acid (TNBS)-induced colitis. To assess gut sensitivity, the electromyography recordings of visceromotor reaction to colorectal distension (CRD) and extracellular microelectrode recordings of CRD-evoked caudal medulla neuronal responses were performed in conscious and urethane-anesthetized animals respectively. The results showed that in intestinal hypersensitive rats the visceromotor reaction and medullary neuronal responses to CRD in 40-60 days after TNBS treatment, despite the absence of obvious gut damage by this time, were increased compared with those in norm. Subcutaneous injection of buspirone (2 mg/kg), which exerted antinociceptive effect in healthy control group, further enhanced visceromotor reaction to CRD in post-colitis animals. In neurophysiological experiments on intestinal hypersensitivity rats, activation of the 5-HT1A receptors by intravenously administered buspirone (2 and 4 mg/kg) resulted in a dose-dependent increase of the CRD-evoked activity in the majority of the caudal medullary neurons, suggesting that the pro-algesic effect of the drug can at least partially be mediated by its excitatory action at the supraspinal level. These data demonstrate that the 5-HT1A agonist buspirone loses its antinociceptive properties in post-colitis conditions and thus may not be useful for reliving visceral hypersensitivity and hyperalgesia in PI-IBS.

If not now, when? Enhancing cardiologists’ psychological well-being as a COVID-19 gain

<h3>Abstract</h3> Stellate ganglia within the intrathoracic cardiac control system receive and integrate central, peripheral, and cardiopulmonary information to produce postganglionic cardiac sympathetic inputs. Pathological anatomical and structural remodeling occurs within...

P.164 Automatic detection of neuronal activity in baseline and seizure-evoked conditions by extracellular microelectrode recording and computer processing in rats

P.164 Automatic detection of neuronal activity in baseline and seizure-evoked conditions by extracellular microelectrode recording and computer processing in rats

Identification of Microrecording Artifacts with Wavelet Analysis and Convolutional Neural Network: An Image Recognition Approach

Abstract Deep brain stimulation (DBS) is an internationally accepted form of treatment option for selected patients with Parkinson’s disease and dystonia. Intraoperative extracellular microelectrode recordings (MER) are considered as the standard electrophysiological method for the precise positioning of the DBS electrode into the target brain structure. Pre-processing of MERs is a key phase in clinical analysis, with intraoperative microelectrode recordings being prone to several artifact groups (up to 25 %). The aim of this methodological article is to provide a convolutional neural network (CNN) processing pipeline for the detection of artifacts in an MER. We applied continuous wavelet transform (CWT) to generate an over-complete time–frequency representation. We demonstrated that when attempting to find artifacts in an MER, the new CNN + CWT provides a high level of accuracy (ACC = 88.1 %), identifies individual classes of artifacts (ACC = 75.3 %) and also offers artifact time onset detail, which can lead to a reduction in false positives/negatives. In summary, the presented methodology is capable of identifying and removing various artifacts in a comprehensive database of MER and represents a substantial improvement over the existing methodology. We believe that this approach will assist in the proposal of interesting clinical hypotheses and will have neurologically relevant effects.

Microelectrode Neuronal Activity of the Internal Globus Pallidus in Dystonia Correlates with Postoperative Neuromodulation Effects and Placement of the Stimulation Electrode

BackgroundDeep brain stimulation (DBS) is emerging as a viable treatment option for selected patients with dystonia. Intraoperative extracellular microelectrode recordings (MER) are considered as the standard electrophysiological method for the precise positioning of the DBS electrode into the target brain structure. Accurate targeting of the permanent stimulation electrode into the Globus Pallidus internus (GPi) is key to positive long-term effects. The suitability of the location is peroperatively assessed by microelectrodes that register single-unit neuronal activity. The aim of this article is to analyse electrophysiological recordings of patient's neuronal activity with a focus on the identification of markers relevant to the patient's clinical state. MethodsIn this study, 13 patients chronically treated with double-sided DBS GPi were examined with a microrecording. The signal (24 kHz) processing, included bandpass filtering (0.5–5 kHz), automated detection of artefacts and feature extraction. Pre-processed signals were analysed by means of statistical learning. ResultsThe results show that the GPi was distinguished from its vicinity with p < 0.001 and 3 machine learning models AUCs had an accuracy of higher than 0.87. The observed biomarker, Hjort mobility, additionally correlated with the long-term neuromodulation effect (rho = −0.4; p < 0.05). Furthermore, we revealed a change of neural activity associated with the active distal DBS contact localization along the medio-lateral direction. ConclusionThis paper demonstrates the quantitative relationship between electrophysiological findings and the clinical effects of pallidal stimulation in dystonia and suggested objectification predictors of the effectiveness of this therapy.

Downregulation of Purkinje Cell Activity by Modulators of Small Conductance Calcium-Activated Potassium Channels In Rat Cerebellum

Small-conductance calcium-activated potassium channels (SK channels) are widely expressed in CNS tissues. Their functions, however, have not been well studied. Participation of SK channels in Purkinje cell (PC) pacemaker activity has been studied predominantly in vitro. Here we studied for the first time the effects of SK channel activation by NS309 or CyPPA on the PC simple spike frequency in vivo in adult (3 - 6 months) and aged (22 - 28 months) rats using extracellular microelectrode recordings. Both pharmacological agents caused a statistically significant decrease in the PC simple spike frequency. The maximum value of the decrease in the simple spike frequency did not depend on age, whereas a statistically significant inhibition of the spike frequency was achieved faster in aged animals than in adult ones. In experiments on cultured neurons PCs were identified by the expression of calbindin as the PC-specific marker. Registration of transmembrane currents in cerebellar neurons revealed the direct action of NS309 and CyPPA on the SK channels of PC consisted in the enhancement of outward potassium currents and action potential after-hyperpolarization. Thus, SK channel activators can compensate for age-related changes of the autorhythmic functions of the cerebellum.

Response inhibition rapidly increases single-neuron responses in the subthalamic nucleus of patients with Parkinson's disease

The subthalamic nucleus (STN) plays a critical role during action inhibition, perhaps by acting like a fast brake on the motor system when inappropriate responses have to be rapidly suppressed. However, the mechanisms involving the STN during motor inhibition are still unclear, particularly because of a relative lack of single-cell responses reported in this structure in humans. In this study, we used extracellular microelectrode recordings during deep brain stimulation surgery in patients with Parkinson's disease (PD) to study STN neurophysiological correlates of inhibitory control during a stop signal task. We found two neuronal subpopulations responding either during motor execution (GO units) or during motor inhibition (STOP units). GO units fired selectively before patients' motor responses whereas STOP units fired selectively when patients successfully withheld their move at a latency preceding the duration of the inhibition process. These results provide electrophysiological evidence for the hypothesized role of the STN in current models of response inhibition.

Supervised segmentation of microelectrode recording artifacts using power spectral density.

Appropriate detection of clean signal segments in extracellular microelectrode recordings (MER) is vital for maintaining high signal-to-noise ratio in MER studies. Existing alternatives to manual signal inspection are based on unsupervised change-point detection. We present a method of supervised MER artifact classification, based on power spectral density (PSD) and evaluate its performance on a database of 95 labelled MER signals. The proposed method yielded test-set accuracy of 90%, which was close to the accuracy of annotation (94%). The unsupervised methods achieved accuracy of about 77% on both training and testing data.

Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop.

Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

Extracellular Signal-Regulated Kinase (ERK) Activity During Sleep Consolidates Cortical Plasticity In Vivo

Ocular dominance plasticity (ODP) in the cat primary visual cortex (V1) is induced during waking by monocular deprivation (MD) and consolidated during subsequent sleep. The mechanisms underlying this process are incompletely understood. Extracellular signal-regulated kinase (ERK) is activated in V1 during sleep after MD, but it is unknown whether ERK activation during sleep is necessary for ODP consolidation. We investigated the role of ERK in sleep-dependent ODP consolidation by inhibiting the ERK-activating enzyme MEK in V1 (via U0126) during post-MD sleep. ODP consolidation was then measured with extracellular microelectrode recordings. Western blot analysis was used to confirm the efficacy of U0126 and to examine proteins downstream of ERK. U0126 abolished ODP consolidation and reduced both phosphorylation of eukaryotic initiation factor 4E (eIF4E) and levels of the synaptic marker PSD-95. Furthermore, interfering with ERK-mediated translation by inhibiting MAP kinase-interacting kinase 1 (Mnk1) with CGP57380 mimicked the effects of U0126. These results demonstrate that ODP consolidation requires sleep-dependent activation of the ERK-Mnk1 pathway.

Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats

Epidemiological investigations have indicated that aluminum (Al), as an important environmental neurotoxicant, could cause damage to the cognitive function which was closely related with neurodegenerative diseases. Long-term potentiation (LTP) is one form of synaptic plasticity in association with cognitive function. Previous studies have demonstrated that Al impaired early phase long-term potentiation (E-LTP) in vivo and in vitro. However, Al-induced damage to late phase long-term potentiation (L-LTP) has poorly been studied. The present study was designed to observe the effects of subchronic Al exposure on the spatial memory, hippocampus ultrastructure and L-LTP in rats. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation from parturition to weaning for 3 weeks and then fed with the distilled water containing 0, 0.2%, 0.4% and 0.6% aluminum chloride (AlCl3) respectively from weaning to postnatal 3 months. The levels of Al in blood and hippocampus were quantitated by atomic absorption spectrophotometer. Morris water maze test was performed to study spatial memory. The induction and maintenance of L-LTP in area of Schaffer collateral- CA1 synapse was recorded by extracellular microelectrode recording technology in hippocampus of experimental rats. Hippocampus was collected for transmission electron microscopy observation. The results showed that the Al concentrations in blood and hippocampus of Al-exposed rats were higher than those of the control rats. Al could impair spatial memory ability of rats. Neuronal and synaptic ultrastructure from Al-exposed rats presented pathological changes; the incidence of L-LTP has a decrease trend while population spike (PS) amplitude was much smaller significantly stimulated by high-frequency stimulation (HFS) in Al-exposed rats. Our findings showed that Al exposure caused spatial memory damage, under which the neuronal and synaptic ultrastructure changes maybe were their morphological basis and the impaired L-LTP of hippocampus could be their electrophysiological basis.

Simulating extracellular microelectrode recordings on cardiac tissue preparations in a bidomain model

Simulating extracellular microelectrode recordings on cardiac tissue preparations in a bidomain model

Theoretical analysis of intracortical microelectrode recordings

Advanced fabrication techniques have now made it possible to produce microelectrode arrays for recording the electrical activity of a large number of neurons in the intact brain for both clinical and basic science applications. However, the long-term recording performance desired for these applications is hindered by a number of factors that lead to device failure or a poor signal-to-noise ratio (SNR). The goal of this study was to identify factors that can affect recording quality using theoretical analysis of intracortical microelectrode recordings of single-unit activity. Extracellular microelectrode recordings were simulated with a detailed multi-compartment cable model of a pyramidal neuron coupled to a finite-element volume conductor head model containing an implanted recording microelectrode. Recording noise sources were also incorporated into the overall modeling infrastructure. The analyses of this study would be very difficult to perform experimentally; however, our model-based approach enabled a systematic investigation of the effects of a large number of variables on recording quality. Our results demonstrate that recording amplitude and noise are relatively independent of microelectrode size, but instead are primarily affected by the selected recording bandwidth, impedance of the electrode–tissue interface and the density and firing rates of neurons surrounding the recording electrode. This study provides the theoretical groundwork that allows for the design of the microelectrode and recording electronics such that the SNR is maximized. Such advances could help enable the long-term functionality required for chronic neural recording applications.

Neuronal code of spatial visual information in the caudate nucleus

Earlier reports described huge overlapping visual receptive fields and the absence of retinotopic organization in the dorsolateral, caudal part of the caudate nucleus. In the present study we suggest a possible alternative mechanism for the coding of spatial visual information. Extracellular microelectrode recordings were carried out in halothane-anesthetized, immobilized, artificially ventilated cats. In order to investigate the responsiveness of the single neurons to visual information arriving from different sites of the receptive field, we divided the visual fields to 20 parts of equal size and stimulated the individual parts one-by-one. We found that each single visual caudate nucleus (CN) neuron can carry information about stimulus locations throughout the whole physically approachable visual field of the investigated eye. A large majority (85%) of these neurons exhibited significantly different responses to stimuli appearing in different regions of their huge receptive field. Thus these neurons appear to have the ability to provide information on the site of the stimulus via their discharge rate. The huge receptive fields in combination with the spatial selectivity suggest that these caudate nucleus neurons may serve as panoramic localizers. On the population level, the sites of maximal responsiveness of the visual neurons are distributed over the whole extent of the receptive fields. We argue that groups of these panoramic localizer neurons with different locations of maximal stimulus preference should have the ability to accurately code the locations of visual stimuli. We propose this distributed population code of visual information as an alternative information processing mechanism.

Methods for predicting cortical UP and DOWN states from the phase of deep layer local field potentials

During anesthesia, slow-wave sleep and quiet wakefulness, neuronal membrane potentials collectively switch between de- and hyperpolarized levels, the cortical UP and DOWN states. Previous studies have shown that these cortical UP/DOWN states affect the excitability of individual neurons in response to sensory stimuli, indicating that a significant amount of the trial-to-trial variability in neuronal responses can be attributed to ongoing fluctuations in network activity. However, as intracellular recordings are frequently not available, it is important to be able to estimate their occurrence purely from extracellular data. Here, we combine in vivo whole cell recordings from single neurons with multi-site extracellular microelectrode recordings, to quantify the performance of various approaches to predicting UP/DOWN states from the deep-layer local field potential (LFP). We find that UP/DOWN states in deep cortical layers of rat primary auditory cortex (A1) are predictable from the phase of LFP at low frequencies (< 4Hz), and that the likelihood of a given state varies sinusoidally with the phase of LFP at these frequencies. We introduce a novel method of detecting cortical state by combining information concerning the phase of the LFP and ongoing multi-unit activity.