Firing Patterns Of Single Neurons Research Articles

Machine learning decoding of single neurons in the thalamus for speech brain-machine interfaces

Objective. Our goal is to decode firing patterns of single neurons in the left ventralis intermediate nucleus (Vim) of the thalamus, related to speech production, perception, and imagery. For realistic speech brain-machine interfaces (BMIs), we aim to characterize the amount of thalamic neurons necessary for high accuracy decoding. Approach. We intraoperatively recorded single neuron activity in the left Vim of eight neurosurgical patients undergoing implantation of deep brain stimulator or RF lesioning during production, perception and imagery of the five monophthongal vowel sounds. We utilized the Spade decoder, a machine learning algorithm that dynamically learns specific features of firing patterns and is based on sparse decomposition of the high dimensional feature space. Main results. Spade outperformed all algorithms compared with, for all three aspects of speech: production, perception and imagery, and obtained accuracies of 100%, 96%, and 92%, respectively (chance level: 20%) based on pooling together neurons across all patients. The accuracy was logarithmic in the amount of neurons for all three aspects of speech. Regardless of the amount of units employed, production gained highest accuracies, whereas perception and imagery equated with each other. Significance. Our research renders single neuron activity in the left Vim a promising source of inputs to BMIs for restoration of speech faculties for locked-in patients or patients with anarthria or dysarthria to allow them to communicate again. Our characterization of how many neurons are necessary to achieve a certain decoding accuracy is of utmost importance for planning BMI implantation.

Optogenetically Controlled Activity Pattern Determines Survival Rate of Developing Neocortical Neurons.

A substantial proportion of neurons undergoes programmed cell death (apoptosis) during early development. This process is attenuated by increased levels of neuronal activity and enhanced by suppression of activity. To uncover whether the mere level of activity or also the temporal structure of electrical activity affects neuronal death rates, we optogenetically controlled spontaneous activity of synaptically-isolated neurons in developing cortical cultures. Our results demonstrate that action potential firing of primary cortical neurons promotes neuronal survival throughout development. Chronic patterned optogenetic stimulation allowed to effectively modulate the firing pattern of single neurons in the absence of synaptic inputs while maintaining stable overall activity levels. Replacing the burst firing pattern with a non-physiological, single pulse pattern significantly increased cell death rates as compared to physiological burst stimulation. Furthermore, physiological burst stimulation led to an elevated peak in intracellular calcium and an increase in the expression level of classical activity-dependent targets but also decreased Bax/BCL-2 expression ratio and reduced caspase 3/7 activity. In summary, these results demonstrate at the single-cell level that the temporal pattern of action potentials is critical for neuronal survival versus cell death fate during cortical development, besides the pro-survival effect of action potential firing per se.

Contribution of AMPA and NMDA receptors in the spontaneous firing patterns of single neurons in autaptic culture

Single neurons in an autaptic culture exhibit various types of firing pattern with different firing durations and rhythms. However, a neuron with autapses has often been modeled as an oscillator providing a monotonic firing pattern with a constant periodicity because of the lack of a mathematical model. In the work described in this study, we use computational simulation and whole-cell patch-clamp recording to elucidate and model the mechanism by which such neurons generate various firing pattens. In the computational simulation, three types of spontaneous firing pattern, i.e., short, long-lasting, and periodic burst firing patterns are realized by changing the combination ratio of N-methyl-d-aspartate (NMDA) to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) conductance. These three types of firing patterns are also observed in the experiments where neurons are cultured in isolation on micropatterned substrates. Using the AMPA and NMDA current models, we discuss that, in principle, autapses can regulate rhythmicity and information selection in neuronal networks.

Neural representations of time-linked memory.

Many cognitive processes, such as episodic memory and decision making, rely on the ability to form associations between two events that occur separately in time. The formation of such temporal associations depends on neural representations of three types of information: what has been presented (trace holding), what will follow (temporal expectation), and when the following event will occur (explicit timing). The present review seeks to link these representations with firing patterns of single neurons recorded while rodents and non-human primates associate stimuli, outcomes, and motor responses over time intervals. Across these studies, two distinct firing patterns were observed in the hippocampus, neocortex, and striatum: some neurons change firing rates during or shortly after the stimulus presentation and sustain the firing rate stably or sidlingly during the subsequent intervals (tonic firings). Other neurons transiently change firing rates during a specific moment within the time intervals (phasic firings), and as a group, they form a sequential firing pattern that covers the entire interval. Clever task designs used in some of these studies collectively provide evidence that both tonic and phasic firing responses represent trace holding, temporal expectation, and explicit timing. Subsequently, we applied machine-learning based classification approaches to the two firing patterns within the same dataset collected from rat medial prefrontal cortex during trace eyeblink conditioning. This quantitative analysis revealed that phasic-firing patterns showed greater selectivity for stimulus identity and temporal position than tonic-firing patterns. Our summary illuminates distributed neural representations of temporal association in the forebrain and generates several ideas for future investigations.

Effects of single neuron firing patterns on network dynamics

The interaction of activities at multiple levels, ranging from molecular to cellular to network level, is a fundamental aspect of information processing in the brain. In vitro studies show that the firing patterns of neurons in response to an input current are highly diverse. Recent experimental data suggest that parvalbumin and somatostatin expressing interneurons, differing in their connectivity and firing patterns, influence the orientation selectivity of pyramidal neurons differently. However, under which conditions low-level neuron properties like spiking patterns affect the network activity dynamics remains to be understood. Therefore, we studied the dynamics of spiking neuronal networks (SNN) by systematically varying the firing pattern of inhibitory interneurons from fast spiking to bursting, keeping the excitatory population as regular spiking. In an SNN with sparse and homogeneous connectivity, global network properties such as population synchrony and mean firing rates did not show significant differences with variations in the type of inhibitory neurons. Interestingly, local properties such as burstiness of the individual neurons were determined by the global network state for instance in the asynchronous activity state both fast spiking neurons and bursting neurons exhibited similar spiking patterns. Thus, the global network state, instead of the neurons' intrinsic properties, determined the spiking pattern of the neurons. Because the effect of neuronal spike patterns could be obscured by the random and homogeneous connectivity, we considered two specific deviations: First we introduced hubs into the network by allowing the fast spiking and bursting neurons to form up to eight times more connections. The overall out degree in such a network with hubs was kept the same as in the random homogeneous networks. Such topology did not affect the network dynamics qualitatively. Next, we separated the inhibitory population into two sub-populations, connected in feedforward (FF) and feedback (FB) manner. With this connectivity scheme, we initially found that neuronal spike patterns can affect the oscillation frequency of the population activity if the fast spiking inhibitory neurons were present as the FB population and FF population was altered between the various ratios of fast spiking and bursting neurons. However, the differences in the oscillations frequency could be attributed to the different gain of the two types of neurons. That is, it was an effect of differences in the degree of recurrent inhibition and not that of spiking activity patterns. In summary, our results suggest that for random homogeneous and the two types of inhomogeneous recurrent SNNs, the individual neuronal patterns do not affect the global dynamics. Any differences in global dynamics with change in single neuron firing patterns is due to the ensuing difference in the firing rate of the neuron types. On the other hand, the global activity state influenced the local parameters like burstiness.

Voltage-sensitive dye imaging reveals shifting spatiotemporal spread of whisker-induced activity in rat barrel cortex

In rats, navigating through an environment requires continuous information about objects near the head. Sensory information such as object location and surface texture are encoded by spike firing patterns of single neurons within rat barrel cortex. Although there are many studies using single-unit electrophysiology, much less is known regarding the spatiotemporal pattern of activity of populations of neurons in barrel cortex in response to whisker stimulation. To examine cortical response at the population level, we used voltage-sensitive dye (VSD) imaging to examine ensemble spatiotemporal dynamics of barrel cortex in response to stimulation of single or two adjacent whiskers in urethane-anesthetized rats. Single whisker stimulation produced a poststimulus fluorescence response peak within 12-16 ms in the barrel corresponding to the stimulated whisker (principal whisker). This fluorescence subsequently propagated throughout the barrel field, spreading anisotropically preferentially along a barrel row. After paired whisker stimulation, the VSD signal showed sublinear summation (less than the sum of 2 single whisker stimulations), consistent with previous electrophysiological and imaging studies. Surprisingly, we observed a spatial shift in the center of activation occurring over a 10- to 20-ms period with shift magnitudes of 1-2 barrels. This shift occurred predominantly in the posteromedial direction within the barrel field. Our data thus reveal previously unreported spatiotemporal patterns of barrel cortex activation. We suggest that this nontopographical shift is consistent with known functional and anatomic asymmetries in barrel cortex and that it may provide an important insight for understanding barrel field activation during whisking behavior.

26. In vivo study of the impact of amygdala kindling on the firing pattern of single neurons in the thalamus in a genetic absence epilepsy rat model

26. In vivo study of the impact of amygdala kindling on the firing pattern of single neurons in the thalamus in a genetic absence epilepsy rat model

Delay Activity in Rodent Frontal Cortex During a Simple Reaction Time Task

To understand how different parts of the frontal cortex control the timing of action, we characterized the firing patterns of single neurons in two areas of rodent frontal cortex-dorsomedial prefrontal cortex (dmPFC) and motor cortex-during a simple reaction time task. Principal component analysis was used to identify major patterns of delay-related activity in frontal cortex: ramping activity and sustained delay activity. These patterns were similar in dmPFC and motor cortex and did not change as animals learned to respond at novel delays. Many neurons in both areas were modulated early in the delay period. Other neurons were modulated in a persistent manner over the duration of the delay period. Delay-related modulations started earlier in motor cortex than in dmPFC and terminated around different task events (at the time of release in dmPFC, just before release of the lever in motor cortex). A subpopulation of neurons was found in dmPFC, but not motor cortex, that fired in response to the trigger stimulus. These results suggest that populations of neurons in rodent frontal cortex are coordinated during delay periods to enable proactive inhibitory control of action.

The use of neural networks for the determination of the signal modulation frequency from the firing activity pattern in the auditory neurons of the frog

A two-layer backward propagation neural network was used for the determination of the modulation frequency of tonal signals from the firing patterns of single neurons located in the cochlear nuclei and the torus semicircularis of the grass frog (Rana t. temporaria). As an input of the neural network, a sum of several single responses of a neuron to an amplitude-modulated stimulus was used. The number of inputs corresponded to the number of the time readouts of the summarized response (usually 60), and the number of output elements corresponded to the number of modulation frequencies to be distinguished (from 3 to 15). In the case of a good synchronization of the input firing activity with the signal envelope, the classification was successful even if the training and classification were performed with the use of individual responses. An increase in the number of summed responses to 10–20 lead to a simplification of the training procedure. The results of the study were discussed in the context of the problem of the formation of periodicity detectors at the upper levels of the auditory pathway in vertebrates.

Medullary pacemaker neurons are essential for both eupnea and gasping in mammals vs. medullary pacemaker neurons are essential for gasping, but not eupnea, in mammals

The following letters are in response to the Point:Counterpoint “Medullary pacemaker neurons are essential for both eupnea and gasping in mammals vs. medullary pacemaker neurons are essential for gasping, but not eupnea, in mammals” that appears in this issue. To the Editor : Eupnea is

A note on minimum-variance theory and beyond

We revisit the minimum-variance theory proposed by Harris and Wolpert (1998 Nature 394 780–4), discuss the implications of the theory on modelling the firing patterns of single neurons and analytically find the optimal control signals, trajectories and velocities. Under the rate coding assumption, input control signals employed in the minimum-variance theory should be Fitts processes rather than Poisson processes. Only if information is coded by interspike intervals, Poisson processes are in agreement with the inputs employed in the minimum-variance theory. For the integrate-and-fire model with Fitts process inputs, interspike intervals of efferent spike trains are very irregular. We introduce diffusion approximations to approximate neural models with renewal process inputs and present theoretical results on calculating moments of interspike intervals of the integrate-and-fire model. Results in Feng, et al (2002 J. Phys. A: Math. Gen. 35 7287–304) are generalized. In conclusion, we present a complete picture on the minimum-variance theory ranging from input control signals, to model outputs, and to its implications on modelling firing patterns of single neurons.

A Reciprocal Relationship between Reliability and Responsiveness in Developing Visual Cortical Neurons

As the visual cortex matures, developmental modifications change the visually evoked firing patterns of single neurons. To explore the relationship between these developmental changes and the fidelity with which neurons transmit information, we measured the reliability of neuronal responses during postnatal development. Infant neurons have lower variability and higher dependence of transmitted information on firing rate than adult cells. Fewer spikes are needed by the infant cortex to convey the same amount of information. The increase in firing rates that occurs during development is largely offset, therefore, by a decrease in the reliability of responses. We propose that these changes are a consequence of the increasing ability of cortical cells to encode rapid changes in the visual environment.

Synchronization of noise-induced bursts in noncoupled sensory neurons.

We report experimental observation of phase synchronization in an array of nonidentical noncoupled noisy neuronal oscillators, due to stimulation with external noise. The synchronization derives from a noise-induced qualitative change in the firing pattern of single neurons, which changes from a quasiperiodic to a bursting mode. We show that at a certain noise intensity the onsets of bursts in different neurons become synchronized, even though the number of spikes inside the bursts may vary for different neurons. We demonstrate this effect both experimentally for the electroreceptor afferents of paddlefish, and numerically for a canonical phase model, and characterize it in terms of stochastic synchronization.

Neural Correlates of Olfactory Recognition Memory in the Rat Orbitofrontal Cortex

The orbitofrontal cortex (OF) is strongly and reciprocally connected with the perirhinal (PR) and entorhinal areas of the medial temporal lobe and plays an important role in odor recognition memory. This study characterized firing patterns of single neurons in the OF of rats performing a continuous odor-guided delayed nonmatch to sample (DNMS) task. Most OF neurons fired in association with one or more task events, including the initiation of trials, the sampling of odor stimuli, and the consumption of rewards. OF neurons also exhibited sustained odor-selective activity during the memory delay, and a large proportion of OF cells had odor-specific enhanced or suppressed responses on stimulus repetition. Most OF neurons were activated during several task events, or associated with complex behavioral states. The incidence of cells that fired in association with the critical match/non-match judgement was increased as the DNMS rule was learned, and was higher in OF than in perirhinal and entorhinal cortex. Furthermore, the classification of match and nonmatch trials was correlated with accuracy in performance of that judgement. These findings are consistent with the view that OF is a high order association cortex that plays a role both in the memory representations for specific stimuli and in the acquisition and application of task rules.

A joint interspike interval difference stochastic spike train analysis: detecting local trends in the temporal firing patterns of single neurons.

We introduce a stochastic spike train analysis method called joint interspike interval difference (JISID) analysis. By design, this method detects changes in firing interspike intervals (ISIs), called local trends, within a 4-spike pattern in a spike train. This analysis classifies 4-spike patterns that have similar incremental changes. It characterizes the higher-order serial dependence in spike firing relative to changes in the firing history. Mathematically, this spike train analysis describes the statistical joint distribution of consecutive changes in ISIs, from which the serial dependence of the changes in higher-order intervals can be determined. It is similar to the joint interspike interval (JISI) analysis, except that the joint distribution of consecutive ISI differences (ISIDs) is quantified. The graphical location of points in the JISID scatter plot reveals the local trends in firing (i.e., monotonically increasing, monotonically decreasing, or transitional firing). The trajectory of these points in the serial-JISID plot traces the time evolution of these trends represented by a 5-spike pattern, while points in the JISID scatter plot represent trends of a 4-spike pattern. We provide complete theoretical interpretations of the JISID analysis. We also demonstrate that this method indeed identifies firing trends in both simulated spike trains and spike trains recorded from cultured neurons.

Effects of small concentrations of volatile anesthetics on action potential firing of neocortical neurons in vitro.

Volatile general anesthetics depress neuronal activity in the mammalian central nervous system and enhance inhibitory Cl- currents flowing across the gamma-aminobutyric acid A (GABA(A)) receptor-ion channel complex. The extent to which an increase in GABA(A)-mediated synaptic inhibition contributes to the decrease in neuronal firing must be determined, because many further effects of these agents have been reported on the molecular level. The actions of halothane, isoflurane, and enflurane on the firing patterns of single neurons were investigated by extracellular recordings in organotypic slice cultures derived from the rat neocortex. Volatile anesthetics depressed spontaneous action potential firing of neocortical neurons in a concentration-dependent manner. The estimated median effective concentration (EC50) values were about one half the EC50 values for general anesthesia. In the presence of the GABA(A) antagonist bicuculline (20 microM), the effectiveness of halothane, isoflurane, and enflurane in reducing the discharge rates were diminished by 48-65%, indicating that these drugs act via the GABA(A) receptor. Together with recent investigations, our results provide evidence that halothane, isoflurane, and enflurane reduced spontaneous action potential firing of neocortical neurons in cultured brain slices mainly by increasing GABA(A)-mediated synaptic inhibition. At concentrations, approximately one half the EC50 for general anesthesia, volatile anesthetics increased overall GABA(A)-mediated synaptic inhibition about twofold, thus decreasing spontaneous action potential firing by half.

Information coding in the rodent prefrontal cortex. II. Ensemble activity in orbitofrontal cortex.

1. Neural activity was recorded from the orbitofrontal cortex (OF) of rats performing an eight-odor discrimination task that included predictable associations between particular odor pairs. A modified linear discriminant analysis was employed to characterize the population response in each trial of the task as a point in an N-dimensional activity space with the firing rate of each cell in the population represented on one of the N dimensions. The ability of the ensemble to discriminate among conditions of a variable was reflected in the tendency of population responses to cluster together in this activity space for repetitions of a given condition. We assessed coding of several variables describing the period of odor sampling, focusing on aspects of current, past, and future events reflected in single-neuron firing patterns, in ensembles composed of 22-138 cells active during the period when the rats sampled the discriminative stimulus in each trial. 2. OF ensembles performed well at discriminating variables with relevance to task demands represented in single-neuron firing patterns, specifically the physical attributes and assigned reward contingency of the current odor as well as the expectation of reward in the following trial that could be inferred from the predictable associations between particular pairs of odors. OF ensembles were able to correctly identify the identity and assigned reward contingency of the current odor in up to 52% (chance = 12.5%) and 99% (chance = 50%) of all trials, respectively, such that the observed behavioral performance required a population of 5,364 odor-responsive cells in the case of odor identity and only 40 cells in the case of valence. Expectations regarding upcoming rewards based on both assigned response contingency and associations between particular pairs of odors were correctly classified in up to 67% (chance = 20%) of all trials such that the observed level of behavioral performance required a population of 3,169 cells. 3. Other information represented in the single-neuron firing patterns, such as the identity and reward contingency of the preceding odor and specific odor-odor associations, was poorly encoded by OF ensembles. Thus neural ensembles in OF may represent only some of the information reflected in single-neuron activity. Stable coding of only the most useful and relevant information by the ensemble might emerge from the tuning properties of single neurons under the influence of the task at hand, producing in the well-trained animal the observed pattern of broad and diverse coding by single neurons and selective, task-relevant coding by neural ensembles in OF.

Modulation of spike frequencies by varying the ambient magnetic field and magnetite candidates in bees ( Tapis mellifera)

1. 1. Spontaneous activity was recorded from neurons in the second abdominal ganglion of bees. 2. 2. Thirty per cent intensity modulations of the horizontal component of the background magnetic field provoked changes in the firing pattern of single neurons. 3. 3. Two classes of neurons were distinguished and confirmed by statistical analysis. 4. 4. Electron dense material in hairs and in or near the cutex may be single domain (SD) and superparamagnetic (SPM) magnetite. 5. 5. A hypothesis is proposed for magnetoreception. Magnetite would act as an amplifier of the external magnetic induction changes. 6. 6. The amplified magnetic field would influence neuronal elements only in restricted regions near the magnetite.

Operant conditioning of single unit activity in parietal cortex

Two rhesus monkeys were trained to control firing patterns of single neurons in parietal cortex (areas 1, 2, 3, 5, 7) using an operant task previously applied to the study of precental units. Twenty-four of 56 (43%) postcentral cells were controlled in contrast to 71 of 136 (52%) precentral units from these and 4 other rhesus monkeys. In addition, monkeys were able to drive precentral units to more sustained tonic firing rates than they could parietal units. An analysis of interspike interval (ISI) distributions showed that, in contrast to precentral units with modal ISIs of 25–50 ms, 50% of parietal units have modal ISIs of 2 ms. Such short ISIs may account for fewer postcentral units reaching control criteria for this particular operant task. Other factors that may contribute to the reduced control of postcentral cells are discussed, particularly the more complex afferent connections to parietal units when compared to precentral pyramidal tract neurons. The data indirectly support conclusions from previous studies that imply that operant control of cortical units is peripherally mediated and does not primarily involve a ‘central’ or ‘open loop’ system.

Response of cat cochlear nucleus neurons to frequency and amplitude modulated tones

Summary Extracellular recordings have been made from cochlear nucleus neurons; during stimulation with (1) static tone bursts of various frequencies and amplitudes, (2) frequency-modulated tones, and (3) amplitude-modulated tones. (1) Neurons have been classified according to the way their latencies and firing patterns depend on tone burst frequency and intensity. In most cases, the effects of frequency change can be mimicked by stimulus amplitude changes. Thus, the firing pattern of single neurons may not uniquely determine both stimulus frequency and intensity. (2) Neurons respond in various ways to amplitude-modulated tonal stimuli. These response characteristics could be correlated with firing patterns of these neurons in response to other stimuli. (3) Spike response patterns to frequency-modulated tonal stimuli fall into three symmetry classes 3 . The translation symmetry response class is shown to be the limiting case for certain stimulus parameters. Spike responses pattern envelopes are invariant as a function of stimulus frequency modulation rate and depth. Both stimulus manipulations result in trivial time scale changes of the response pattern. (4) The experimental data is interpreted in terms of transmissions and detections of properties of the auditory stimulus. The only possible stimulus properly detected by these neurons seems to be the sign of df/dt. Remaining stimulus information is variously available to higher auditory centers. It is suggested that unique determination of stimulus parameters involves at least two or three distinct populations of neurons.