Multichannel Extracellular Recordings Research Articles

Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity.

To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

Multichannel Extracellular Recording in Freely Moving Mice.

The protocol aims to uncover the properties of neuronal firing and network local field potentials (LFPs) in behaving mice carrying out specific tasks by correlating the electrophysiological signals with spontaneous and/or specific behavior. This technique represents a valuable tool in studying the neuronal network activity underlying these behaviors. The article provides a detailed and complete procedure for electrode implantation and consequent extracellular recording in free-moving conscious mice. The study includes a detailed method for implanting the microelectrode arrays, capturing the LFP and neuronal spiking signals in the motor cortex (MC) using a multichannel system, and the subsequent offline data analysis. The advantage of multichannel recording in conscious animals is that a greater number of spiking neurons and neuronal subtypes can be obtained and compared, which allows the evaluation of the relationship between a specific behavior and the associated electrophysiological signals. Notably, the multichannel extracellular recording technique and the data analysis procedure described in the present study can be applied to other brain areas when conducting experiments in behaving mice.

Seeing beyond the spikes: reconstructing the complete spatiotemporal membrane potential distribution from paired intra- and extracellular recordings.

Although electrophysiologists have been recording intracellular neural activity routinely ever since the ground-breaking work of Hodgkin and Huxley, and extracellular multichannel electrodes have also been used frequently and extensively, a practical experimental method to track changes in membrane potential along a complete single neuron is still lacking. Instead of obtaining multiple intracellular measurements on the same neuron, we propose an alternative method by combining single-channel somatic patch-clamp and multichannel extracellular potential recordings. In this work, we show that it is possible to reconstruct the complete spatiotemporal distribution of the membrane potential of a single neuron with the spatial resolution of an extracellular probe during action potential generation. Moreover, the reconstruction of the membrane potential allows us to distinguish between the two major but previously hidden components of the current source density (CSD) distribution: the resistive and the capacitive currents. This distinction provides a clue to the clear interpretation of the CSD analysis, because the resistive component corresponds to transmembrane ionic currents (all the synaptic, voltage-sensitive and passive currents), whereas capacitive currents are considered to be the main contributors of counter-currents. We validate our model-based reconstruction approach on simulations and demonstrate its application to experimental data obtained in vitro via paired extracellular and intracellular recordings from a single pyramidal cell of the rat hippocampus. In perspective, the estimation of the spatial distribution of resistive membrane currents makes it possible to distiguish between active and passive sinks and sources of the CSD map and the localization of the synaptic input currents, which make the neuron fire. KEY POINTS: A new computational method is introduced to calculate the unbiased current source density distribution on a single neuron with known morphology. The relationship between extracellular and intracellular electric potential is determined via mathematical formalism, and a new reconstruction method is applied to reveal the full spatiotemporal distribution of the membrane potential and the resistive and capacitive current components. The new reconstruction method was validated on simulations. Simultaneous and colocalized whole-cell patch-clamp and multichannel silicon probe recordings were performed from the same pyramidal neuron in the rat hippocampal CA1 region, in vitro. The method was applied in experimental measurements and returned precise and distinctive characteristics of various intracellular phenomena, such as action potential generation, signal back-propagation and the initial dendritic depolarization preceding the somatic action potential.

Binocular visual experience drives the maturation of response variability and reliability in the visual cortex

SummaryA fundamental challenge of neuroscience is to understand how a single neuron responds to multiple synaptic inputs effectively and reliably. In primary visual cortex, repeated stimuli to one eye elicit neuronal responses of inherent variability and reliability. However, it remains unclear how this monocular variability and reliability contribute to the establishment of effective and reliable binocular responses and what drives this development. In this study, using in vivo multichannel extracellular recordings, we demonstrate binocular responses in adult mouse visual cortex exhibit low variability and high reliability. This response characteristic is immature during the critical period of binocular vision development. In amblyopic mice, the maturation of binocular variability and reliability is disrupted, and this defect can be partially rescued by enhancing cortical plasticity via dark exposure. In conclusion, the development of cortical response variability and reliability depends on the normal binocular visual experience, which is further regulated by cortical plasticity.

Activity and Coupling to Hippocampal Oscillations of Median Raphe GABAergic Cells in Awake Mice.

Ascending serotonergic/glutamatergic projection from the median raphe region (MRR) to the hippocampal formation regulates both encoding and consolidation of memory and the oscillations associated with them. The firing of various types of MRR neurons exhibits rhythmic modulation coupled to hippocampal oscillatory activity. A possible intermediary between rhythm-generating forebrain regions and entrained ascending modulation may be the GABAergic circuit in the MRR, known to be targeted by a diverse array of top-down inputs. However, the activity of inhibitory MRR neurons in an awake animal is still largely unexplored. In this study, we utilized whole cell patch-clamp, single cell, and multichannel extracellular recordings of GABAergic and non-GABAergic MRR neurons in awake, head-fixed mice. First, we have demonstrated that glutamatergic and serotonergic neurons receive both transient, phasic, and sustained tonic inhibition. Then, we observed substantial heterogeneity of GABAergic firing patterns but a marked modulation of activity by brain states and fine timescale coupling of spiking to theta and ripple oscillations. We also uncovered a correlation between the preferred theta phase and the direction of activity change during ripples, suggesting the segregation of inhibitory neurons into functional groups. Finally, we could detect complementary alteration of non-GABAergic neurons’ ripple-coupled activity. Our findings support the assumption that the local inhibitory circuit in the MRR may synchronize ascending serotonergic/glutamatergic modulation with hippocampal activity on a subsecond timescale.

Differential Effect of Anesthesia on Visual Cortex Neurons with Diverse Population Coupling

Cortical neurons display diverse firing patterns and synchronization properties. How anesthesia alters the firing response of different neuron groups relevant for sensory information processing is unclear. Here we investigated the graded effect of anesthesia on spontaneous and visual flash-induced spike activity of different neuron groups classified based on their spike waveform, firing rate, and population coupling (the extent neurons conform to population spikes). Single-unit activity was measured from multichannel extracellular recordings in deep layers of primary visual cortex of freely moving rats in wakefulness and at three concentrations of desflurane. Anesthesia generally decreased firing rate and increased population coupling and burstiness of neurons. Population coupling and firing rate became more correlated and the pairwise correlation between neurons became more predictable by their population coupling in anesthesia. During wakefulness, visual stimulation increased firing rate; this effect was the largest and the most prolonged in neurons that exhibited high population coupling and high firing rate. During anesthesia, the early increase in firing rate (20–150 ms post-stimulus) of these neurons was suppressed, their spike timing was delayed and split into two peaks. The late response (200–400 ms post-stimulus) of all neurons was also suppressed. We conclude that anesthesia alters the visual response of primarily high-firing highly coupled neurons, which may interfere with visual sensory processing. The increased association of population coupling and firing rate during anesthesia suggests a decrease in sensory information content.

Representation of Haltere Oscillations and Integration with Visual Inputs in the Fly Central Complex.

The reduced hindwings of flies, known as halteres, are specialized mechanosensory organs that detect body rotations during flight. Primary afferents of the haltere encode its oscillation frequency linearly over a wide bandwidth and with precise phase-dependent spiking. However, it is not currently known whether information from haltere primary afferent neurons is sent to higher brain centers where sensory information about body position could be used in decision making, or whether precise spike timing is useful beyond the peripheral circuits that drive wing movements. We show that in cells in the central brain, the timing and rates of neural spiking can be modulated by sensory input from experimental haltere movements (driven by a servomotor). Using multichannel extracellular recording in restrained flesh flies (Sarcophaga bullata of both sexes), we examined responses of central complex cells to a range of haltere oscillation frequencies alone, and in combination with visual motion speeds and directions. Haltere-responsive units fell into multiple response classes, including those responding to any haltere motion and others with firing rates linearly related to the haltere frequency. Cells with multisensory responses showed higher firing rates than the sum of the unisensory responses at higher haltere frequencies. They also maintained visual properties, such as directional selectivity, while increasing response gain nonlinearly with haltere frequency. Although haltere inputs have been described extensively in the context of rapid locomotion control, we find haltere sensory information in a brain region known to be involved in slower, higher-order behaviors, such as navigation.SIGNIFICANCE STATEMENT Many animals use vision for navigation; however, these cues must be interpreted in the context of the body's position. In mammalian brains, hippocampal cells combine visual and vestibular information to encode head direction. A region of the arthropod brain, known as the central complex (CX), similarly encodes heading information, but it is unknown whether proprioceptive information is integrated here as well. We show that CX neurons respond to input from halteres, specialized proprioceptors in flies that detect body rotations. These neurons also respond to visual input, providing one of the few examples of multiple sensory modalities represented in individual CX cells. Haltere stimulation modifies neural responses to visual signals, providing a mechanism for integrating vision with proprioception.

Magnitude and behavior of cross-talk effects in multichannel electrophysiology experiments

Modern neurophysiological experiments frequently involve multiple channels separated by very small distances. A unique methodological concern for multiple-electrode experiments is that of capacitive coupling (cross-talk) between channels. Yet the nature of the cross-talk recording circuit is not well known in the field, and the extent to which it practically affects neurophysiology experiments has never been fully investigated. Here we describe a simple electrical circuit model of simultaneous recording and stimulation with two or more channels and experimentally verify the model using ex vivo brain slice and in vivo whole-brain preparations. In agreement with the model, we find that cross-talk amplitudes increase nearly linearly with the impedance of a recording electrode and are larger for higher frequencies. We demonstrate cross-talk contamination of action potential waveforms from intracellular to extracellular channels, which is observable in part because of the different orders of magnitude between the channels. This contamination is electrode impedance-dependent and matches predictions from the model. We use recently published parameters to simulate cross-talk in high-density multichannel extracellular recordings. Cross-talk effectively spatially smooths current source density (CSD) estimates in these recordings and induces artefactual phase shifts where underlying voltage gradients occur; however, these effects are modest. We show that the effects of cross-talk are unlikely to affect most conclusions inferred from neurophysiology experiments when both originating and receiving electrode record signals of similar magnitudes. We discuss other types of experiments and analyses that may be susceptible to cross-talk, techniques for detecting and experimentally reducing cross-talk, and implications for high-density probe design.NEW & NOTEWORTHY We develop and experimentally verify an electrical circuit model describing cross-talk that necessarily occurs between two channels. Recorded cross-talk increased with electrode impedance and signal frequency. We recorded cross-talk contamination of spike waveforms from intracellular to extracellular channels. We simulated high-density multichannel extracellular recordings and demonstrate spatial smoothing and phase shifts that cross-talk enacts on CSD measurements. However, when channels record similar-magnitude signals, effects are modest and unlikely to affect most conclusions.

Persistent Neuronal Activity in Anterior Cingulate Cortex Correlates with Sustained Attention in Rats Regardless of Sensory Modality

The anterior cingulate cortex (ACC) has long been thought to regulate conflict between an object of attention and distractors during goal-directed sustained attention. However, it is unclear whether ACC serves to sustained attention itself. Here, we developed a task in which the time course of sustained attention could be controlled in rats. Then, using pharmacological lesion experiments, we employed it to assess function of ACC in sustained attention. We then recorded neuronal activity in ACC using multichannel extracellular recording techniques and identified specific ACC neurons persistently activated during the period of attention. Further experiments showed that target modality had minimal influence on the neuronal activity, and distracting external sensory input during the attention period did not perturb persistent neuronal activity. Additionally, minimal trial-to-trial variability in neuronal activity observed during sustained attention supports a role for ACC neurons in that behavior. Therefore, we conclude that the ACC neuronal activity correlates with sustained attention.

Unsupervised neural spike sorting for high-density microelectrode arrays with convolutive independent component analysis

BackgroundUnsupervised identification of action potentials in multi-channel extracellular recordings, in particular from high-density microelectrode arrays with thousands of sensors, is an unresolved problem. While independent component analysis (ICA) achieves rapid unsupervised sorting, it ignores the convolutive structure of extracellular data, thus limiting the unmixing to a subset of neurons. New methodHere we present a spike sorting algorithm based on convolutive ICA (cICA) to retrieve a larger number of accurately sorted neurons than with instantaneous ICA while accounting for signal overlaps. Spike sorting was applied to datasets with varying signal-to-noise ratios (SNR: 3–12) and 27% spike overlaps, sampled at either 11.5 or 23kHz on 4365 electrodes. ResultsWe demonstrate how the instantaneity assumption in ICA-based algorithms has to be relaxed in order to improve the spike sorting performance for high-density microelectrode array recordings. Reformulating the convolutive mixture as an instantaneous mixture by modeling several delayed samples jointly is necessary to increase signal-to-noise ratio. Our results emphasize that different cICA algorithms are not equivalent. Comparison with existing methodsSpike sorting performance was assessed with ground-truth data generated from experimentally derived templates. The presented spike sorter was able to extract ≈90% of the true spike trains with an error rate below 2%. It was superior to two alternative (c)ICA methods (≈80% accurately sorted neurons) and comparable to a supervised sorting. ConclusionOur new algorithm represents a fast solution to overcome the current bottleneck in spike sorting of large datasets generated by simultaneous recording with thousands of electrodes.

Abstract WP279: Disruption of Cortico-hippocampal Functional Connectivity Underlies the Memory Impairment Following Experimental Stroke

Introduction: The cognitive consequences and the underlying mechanisms leading to cognitive impairments after cerebrovascular occlusive diseases are still unclear. Previously we have shown that distal middle cerebral artery occlusion (dMCAO) led to hippocampal hypofunction and spatial memory impairment in the absence of direct hippocampal injury. Hypothesis: In light of the importance of interactions between the cortex and hippocampus during memory processing, we hypothesize that cortical stroke disrupts afferent excitatory input from the lesioned cortical area to other remote brain regions such as the hippocampus, which can be mimicked by pharmacological inactivation of the cortex. Methods: Adult male rats were subjected to either dMCAO or cortical inactivation with AMPA receptor antagonist CNQX, compared to controls by sham-operation or injection with artificial CSF, respectively. Hippocampal function was determined by the social transmission of food preference (STFP) test, activity mapping by Fos imaging and in vivo electrophysiology by multi-channel extracellular recording. Results: dMCAO and cortical inactivation both induced impaired memory performance as measured in the STFP task and reduced hippocampal activation. The memory impairment was not attributed to change in olfaction by stroke or inactivation, since it was not detected in either experimental group. An increase in the bursts of sharp-wave associated ripples (SPW-Rs) was detected during reperfusion after stroke and after CNQX injection. Further, cortical inactivation also induced a shift of the theta phase, suggesting an alteration in the dynamics of hippocampal-cortical interactions. Conclusions: Given the crucial role of hippocampal theta and SPW-Rs in memory function, our results suggest that cortical stroke leads to memory impairment by disrupting the functional connectivity between the cortex and hippocampus, albeit without causing direct injury to the latter.

Antidepressants modulate glycine action in rat hippocampus.

Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current.

Sparse data analysis strategy for neural spike classification.

Many of the multichannel extracellular recordings of neural activity consist of attempting to sort spikes on the basis of shared characteristics with some feature detection techniques. Then spikes can be sorted into distinct clusters. There are in general two main statistical issues: firstly, spike sorting can result in well-sorted units, but by with no means one can be sure that one is dealing with single units due to the number of neurons adjacent to the recording electrode. Secondly, the waveform dimensionality is reduced in a small subset of discriminating features. This shortening dimension effort was introduced as an aid to visualization and manual clustering, but also to reduce the computational complexity in automatic classification. We introduce a metric based on common neighbourhood to introduce sparsity in the dataset and separate data into more homogeneous subgroups. The approach is particularly well suited for clustering when the individual clusters are elongated (that is nonspherical). In addition it does need not to select the number of clusters, it is very efficient to visualize clusters in a dataset, it is robust to noise, it can handle imbalanced data, and it is fully automatic and deterministic.

Encoding wide-field motion and direction in the central complex of the cockroach Blaberus discoidalis.

In the arthropod brain, the central complex (CX) receives various forms of sensory signals and is associated with motor functions, but its precise role in behavior is controversial. The optomotor response is a highly conserved turning behavior directed by visual motion. In tethered cockroaches, 20% procaine injected into the CX reversibly blocked this behavior. We then used multichannel extracellular recording to sample unit activity in the CX in response to wide-field visual motion stimuli, moving either horizontally or vertically at various temporal frequencies. For the 401 units we sampled, we identified five stereotyped response patterns: tonically inhibited or excited responses during motion, phasically inhibited or excited responses at the initiation of motion, and phasically excited responses at the termination of motion. Sixty-seven percent of the units responded to horizontal motion, while only 19% responded to vertical motion. Thirty-eight percent of responding units were directionally selective to horizontal motion. Response type and directional selectivity were sometimes conditional with other stimulus parameters, such as temporal frequency. For instance, 16% of the units that responded tonically to low temporal frequencies responded phasically to high temporal frequencies. In addition, we found that 26% of wide-field motion responding units showed a periodic response that was entrained to the temporal frequency of the stimulus. Our results show a diverse population of neurons within the CX that are variably tuned to wide-field motion parameters. Our behavioral data further suggest that such CX activity is required for effective optomotor responses.

Transcranial Alternating Current Stimulation Modulates Large-Scale Cortical Network Activity by Network Resonance

Transcranial direct current stimulation (tDCS) has emerged as a potentially safe and effective brain stimulation modality that alters cortical excitability by passing a small, constant electric current through the scalp. tDCS creates an electric field that weakly modulates the membrane voltage of a large number of cortical neurons. Recent human studies have suggested that sine-wave stimulation waveforms [transcranial alternating current stimulation (tACS)] represent a more targeted stimulation paradigm for the enhancement of cortical oscillations. Yet, the underlying mechanisms of how periodic, weak global perturbations alter the spatiotemporal dynamics of large-scale cortical network dynamics remain a matter of debate. Here, we simulated large-scale networks of spiking neuron models to address this question in endogenously rhythmic networks. We identified distinct roles of the depolarizing and hyperpolarizing phases of tACS in entrainment, which entailed moving network activity toward and away from a strong nonlinearity provided by the local excitatory coupling of pyramidal cells. Together, these mechanisms gave rise to resonance dynamics characterized by an Arnold tongue centered on the resonance frequency of the network. We then performed multichannel extracellular recordings of multiunit firing activity during tACS in anesthetized ferrets (Mustela putoris furo), a model species with a gyrencephalic brain, to verify that weak global perturbations can selectively enhance oscillations at the applied stimulation frequency. Together, these results provide a detailed mechanistic understanding of tACS at the level of large-scale network dynamics and support the future design of activity-dependent feedback tACS paradigms that dynamically tailor stimulation frequency to the spectral peak of ongoing brain activity.

Arginine vasopressin remolds the spontaneous discharges disturbed by amyloid β protein in hippocampal CA1 region of rats

Beta-amyloid peptide (Aβ) aggregated in the brain is the main pathological characteristic of Alzheimer's disease (AD), and a significant decrease in the concentration of arginine vasopressin (AVP) in the brain of AD patients has been reported. Our recent study shows that intracerebroventricular (i.c.v.) injection of AVP protects against Aβ-induced impairments of spatial learning and memory. However, it is still unclear whether the Aβ-induced cognitive deficit is involved in the alteration of central neuronal discharges, and further whether AVP can modulate the electrophysiological change induced by Aβ. The present study thus observed the effects of AVP, Aβ and AVP plus Aβ on the spontaneous discharges of hippocampal CA1 neurons in rats by using multi-channel extracellular recording technique. The results showed that: (1) the average frequency of spontaneous discharges was decreased by i.c.v. injection of 25nmol Aβ25–35; (2) 10nmol AVP induced an increase in spike discharge in the hippocampal CA1 neurons; (3) pretreatment with 10nmol AVP effectively reversed Aβ25–35 induced suppression of spontaneous discharges in hippocampal CA1 region. These in vivo electrophysiological results indicate that AVP, as a hormone and neurotransmitter, can remold the spontaneous discharges disturbed by Aβ and counteract the deleterious effect of Aβ25–35 on neural circuit, suggesting that the activation of central vasopressinergic system may play a beneficial role for the prevention and treatment of cognitive impairments in AD.

Thalamic Network Oscillations Synchronize Ontogenetic Columns in the Newborn Rat Barrel Cortex

Neocortical areas are organized in columns, which form the basic structural and functional modules of intracortical information processing. Using voltage-sensitive dye imaging and simultaneous multi-channel extracellular recordings in the barrel cortex of newborn rats in vivo, we found that spontaneously occurring and whisker stimulation-induced gamma bursts followed by longer lasting spindle bursts were topographically organized in functional cortical columns already at the day of birth. Gamma bursts synchronized a cortical network of 300-400 µm in diameter and were coherent with gamma activity recorded simultaneously in the thalamic ventral posterior medial (VPM) nucleus. Cortical gamma bursts could be elicited by focal electrical stimulation of the VPM. Whisker stimulation-induced spindle and gamma bursts and the majority of spontaneously occurring events were profoundly reduced by the local inactivation of the VPM, indicating that the thalamus is important to generate these activity patterns. Furthermore, inactivation of the barrel cortex with lidocaine reduced the gamma activity in the thalamus, suggesting that a cortico-thalamic feedback loop modulates this early thalamic network activity.

Automatic spike sorting for extracellular electrophysiological recording using unsupervised single linkage clustering based on grey relational analysis

Automatic spike sorting is a prerequisite for neuroscience research on multichannel extracellular recordings of neuronal activity. A novel spike sorting framework, combining efficient feature extraction and an unsupervised clustering method, is described here. Wavelet transform (WT) is adopted to extract features from each detected spike, and the Kolmogorov–Smirnov test (KS test) is utilized to select discriminative wavelet coefficients from the extracted features. Next, an unsupervised single linkage clustering method based on grey relational analysis (GSLC) is applied for spike clustering. The GSLC uses the grey relational grade as the similarity measure, instead of the Euclidean distance for distance calculation; the number of clusters is automatically determined by the elbow criterion in the threshold-cumulative distribution. Four simulated data sets with four noise levels and electrophysiological data recorded from the subthalamic nucleus of eight patients with Parkinson's disease during deep brain stimulation surgery are used to evaluate the performance of GSLC. Feature extraction results from the use of WT with the KS test indicate a reduced number of feature coefficients, as well as good noise rejection, despite similar spike waveforms. Accordingly, the use of GSLC for spike sorting achieves high classification accuracy in all simulated data sets. Moreover, J–measure results in the electrophysiological data indicating that the quality of spike sorting is adequate with the use of GSLC.

Detection and classification of sensory information from acute spinal cord recordings

One avenue of research for partial restoration of function following spinal cord injury is the use of neural prostheses, an example of which is functional electrical stimulation (FES) devices for motor functions. Neural prostheses may also be useful for the extraction of sensory information directly from the nervous system. We suggest the spinal cord as a possible site for the detection of peripheral sensory information from neural activity alone. Acute multichannel extracellular recordings were used to extract neural spike activity elicited from peripheral sensations from the spinal cords of rats. To test the recording method and classification potential, eight classes of sensory events were recorded consisting of electrical stimulation of seven locations on rat forepaws, and another class of data during which no stimulus was present. A dual-stage classification scheme using principal component analysis and k-Means clustering was devised to classify the sensory events during single trials. The eight tasks were correctly identified at a mean accuracy of 96%. Thus, we have shown the methodology to detect and classify peripheral sensory information from multichannel recordings of the spinal cord. These methods may be useful, for example, in a closed-loop FES for restoration of hand grasp.

The Effects of Tonic Locus Ceruleus Output on Sensory-Evoked Responses of Ventral Posterior Medial Thalamic and Barrel Field Cortical Neurons in the Awake Rat

In mammals, the pontine nucleus locus ceruleus (LC) is the sole source of norepinephrine (NE) projections to the forebrain. Increasing tonic discharge of LC neurons elevates extracellular levels of NE in the cortex and thalamus. Tonic LC discharge is linked to the level of wakefulness and behavioral performance, demonstrating an optimal firing rate during sustained attention tasks. Iontophoretic application of NE to target neurons in the forebrain has been shown to produce a diverse set of neuromodulatory actions, including augmentation of synaptically evoked discharge as well as suppression of spontaneous and stimulus-evoked firing patterns. Iontophoretic studies cataloged potential NE effects; however, the context in which such actions could occur in awake behaving animals remained controversial. To address this issue, the current study examined the effects of increasing tonic LC output on spontaneous and stimulus-evoked discharge of neurons within the ventroposterior medial (VPM) thalamus and barrel field (BF) somatosensory cortex of awake animals using multichannel extracellular recording strategies. The present findings indicate two primary outcomes that result from increasing frequencies of LC stimulation, either an inverted-U facilitating response profile or monotonic suppression of sensory-evoked neuronal responses. Increased tonic LC output generally decreased neuronal response latency measures for both BF cortical and VPM thalamic cells. LC-mediated effects on target VPM and BF cortical neuron sensory processing are consistent with previous demonstrations of NE modulatory actions on central neurons but indicate that such actions are cell specific. Moreover, clear differences were observed between the modulation of VPM and BF cortical cells. These data suggest that sensory signal processing is continually altered over the range of tonic LC discharge frequencies that occur in the waking animal. Such changes may account for LC-mediated shifts in sensory network performance across multiple stages of arousal and attention.