Unit Spike Research Articles

Spatial and Temporal Stochastic Interaction in Neuronal Assemblies

The observation of various types of spatio-temporal correlations in spike-patterns of multiple cortical neurons has shifted attention from rate coding paradigms to computational processes based on the precise timing of spikes in neuronal ensembles. In the present work we develop the notion of “spatial” and “temporal interaction” which provides measures for statistical dependences in coupled stochastic processes like multiple unit spike trains. We show that the classical Willshaw network and Abeles’ synfire chain model both reveal a moderate spatial interaction, but only the synfire chain model reveals a positive temporal interaction, too. Systems that maximize temporal interaction are shown to be almost deterministic globally, but posses almost unpredictable firing behavior on the single unit level.

Influence of dopamine on ventrolateral thalamic inputs in cat motor cortex

Neuronal activity in several brain regions is modulated by dopaminergic inputs. When single neuronal activity/20 trials of single-pulse ventrolateral thalamic (VL) stimulation was extracellularly recorded in the in vivo, anesthetized cat motor cortex, iontophoretic application of dopamine (DA) elicited either suppression or, in a fewer instances, facilitation of evoked unitary responses. The predominant inhibition exerted by DA appeared to be consistent for successive trials, and a D 1, D 2, and D 1/D 2 receptor antagonist restored the effect, thereby reflecting a possible coexistence of two DA receptors. By contrast, only a fewer neurons’ response to DA displayed facilitation, which was not attenuated by DA antagonists. Moreover, subsequent trials with receptor agonist and antagonists induced inconsistent effects. Except for the jitters, single unit spikes showed invariant latency, which was constant during all recording parameters, and the mean latency remained unchanged. The modulatory effects mediated by DA did not reveal any substantial difference between short- and long-latency responses. Both pyramidal tract neurons and non-pyramidal tract neurons, determined on the basis of antidromic potentials from the pyramidal tract, responded to DA essentially in a similar manner. It appears that DA overall inhibits cat motor cortical neuronal activity in response to VL inputs. We propose that such DAergic inhibition of thalamocortical excitation in the motor cortex could be critical for ongoing sensorimotor transformation.

Statistical test for peri-stimulus time histograms in assessing motor neuron activity.

The peri-stimulus time histogram is a valuable tool for evaluating neural connections in humans. To detect the degree to which a conditioning stimulus to a sensory nerve modulates motor neuron activity, a histogram of motor unit spike intervals after a conditioning stimulus is measured. This histogram allows the effect of the conditioning stimulus to be visualised. By comparison with a reference histogram of motor unit spike intervals after a sham stimulus, the noise caused by spontaneous firing sway can be removed. However, no valid statistical test has yet been developed to separate the physiological effect from the spontaneous sway and statistical noise. A computational method has been proposed to detect modulation caused by a conditioning stimulus. To clarify the effect of a conditioning stimulus, this new method used reference histograms to calculate a confidence interval. A simulated experiment demonstrated that about 2000 re-samplings were sufficient to estimate a confidence interval for a histogram with 1 ms bin width constructed from 300 triggers. Testing of the experimental data, measured from the tibialis anterior muscles during the elicitation of the excitatory spinal reflex, confirmed that significant peaks were produced at 30, 34, 35 and 38ms after the conditioning stimulus. These correspond appropriately to the delay of the spinal reflex.

Synaptically driven spikes and long-term potentiation in neocortical layer 2/3

Recently, variation upon a well-established hippocampal model has given rise to a new paradigm in which the strength of synaptic inputs to neocortical layer 2/3 is estimated in vitro by recording synaptically driven extracellular potentials elicited there by electrical stimulation applied to underlying layer 4. The analysis of these potentials is commonly based upon an assumption that postsynaptic spiking has played no significant role in their generation. Here, we have tested this assumption by quantifying in rats (using data obtained by cell-attached recording) the rate at which unit spikes are elicited in layer 2/3 under commonly used conditions of stimulation and recording. We found that spike responses were regularly elicited at the same latencies as field potential peaks and the rising phases of intracellularly recorded synaptic currents, and the incidence of such spiking (the fractional rate of cells spiking versus cells sampled) was sufficient to give this higher-order activity a major role in determining response amplitudes. We then analyzed layer 2/3 waveform characteristics before and after inducing long-term potentiation (LTP) by theta-burst stimulation (TBS) and found that the induction of LTP succeeded only when the initial response included a strong spike component. We further observed that LTP expression was always accompanied by a pronounced enhancement of such components. Our data suggest that, unlike in hippocampal CA1, LTP elicited by TBS in this neocortical paradigm depends upon modification of synaptically driven spike activity, through either enhanced synchronization of unitary responses, the recruitment of additional responding units, or both. This potentiation of the spike response could arise (as previously proposed) through an increase in the efficacy of synapses mediating projection from layer 4 to 2/3, but other mechanisms may also contribute, such as modification of short-range recurrent connections within layer 2/3, which are likely to play an important role in defining local-network cell ensembles.

Spike sorting: a novel shift and amplitude invariant technique

This paper deals with the spike classification problem encountered in multi-unit recordings of neural activity in the brain. We recently developed a new methodology for estimating and classifying multi-units recorded by means of multichannel silicon probes from the observed spike trains (Proceedings of the ICASSP’01, May 2001, pp. 2813–2816; Proceedings of the IEEE 35th Asilomar Conference on Signals, Systems and Computers, Pacific Grove, CA, November 2001). In this work, we demonstrate the robustness of the technique to single unit spike amplitude variation often encountered in burst activity or long term chronic recordings. In low signal-to-noise ratio scenarios where variability in spike threshold crossings during classical detection is always a problem, we show that the technique is extremely robust to shifts in spike event times. Results showing the efficiency of the algorithm from simulated and experimental data are presented.

A role for non-neuronal cells in synchronization of intracellular calcium oscillations in primate LHRH neurons

A study using multiunit activity recording from the medial basal hypothalamus indicates that pulsatile luteinizing hormone-releasing hormone (LHRH) release is a consequence of synchronized activity of individual LHRH neurons. An increase in single unit spike components extracted from the multiunit “LHRH pulse-generator” activity by cluster analysis occurs as a simultaneous increase in the firing rate of many individual hypothalamic neurons rather than the recruitment of new bursting neurons. The mechanism underlying LHRH synchronization is currently unknown. This is because, unlike oxytocin and vasopressin neurons, LHRH neurons do not form a nucleus in the hypothalamus and there is little evidence for physical contact between LHRH neurons—such as synapses or syncytium formation—that allow the synchronization of LHRH neurons. The perikarya of LHRH neurons are covered by glial sheaths and LHRH neuroterminals are intimately associated with glial end feet. The chapter also explains synchronization of [Ca 2 +] i oscillations and LHRH neurosecretion.

Synchronization of single motor units during voluntary contractions in the upper and lower extremities

Objective: To investigate motor unit synchronization in the time and frequency domains and compare the amount and nature of this synchronization between upper and lower extremity muscles in human subjects.Methods: A total of 120 motor unit pairs from biceps brachii (BB), first dorsal interosseous (1DI), vastus medialis (VM), and tibialis anterior (TA) on the dominant side were analyzed and compared. Pairs of motor unit spike trains were recorded from two concentric needle electrodes inserted within these muscles in healthy volunteers. Subjects were instructed to maintain a weak isometric contraction of these muscles so that an individual motor unit recorded from each concentric needle discharged at a steady rate of approximately 10 impulses/s. Pairs of motor unit spike trains were cross-correlated in the time domain, and coherence analysis in the frequency domain was performed on the same spike train data.Results: Synchronization was seen in all the muscles studied. Strength of motor unit synchronization, expressed as synchronization index (SI), was greater in 1DI muscles compared to other muscles (P<0.01). Coherence analysis revealed significant association between motor unit firings in the 1-5 and 25–30 Hz frequency ranges in all the muscles studied. The incidence of 25–30 Hz coherence peaks were found to be greater for 1DI muscles compared to other muscles.Conclusion: The above results suggest a possible role for corticospinal projections in producing pre-synaptic inputs responsible for synchronization of motor unit firings and 25–30 Hz coherence peaks.

SLOW OSCILLATIONS OF THE PURKINJE CELL FIRING RATE INDUCED BY ELECTRICAL STIMULATION OF THE LOCUS COERULEUS IN RATS

In anesthetized Wistar rats, we studied the effect of electrical stimulation of the locus coeruleus (LC) on the firing rates of Purkinje cells using spectral analysis. The frequency of extracellularly recorded activity of Purkinje cells was measured before and during the 1st, 5th, 6th, and 11th min after cessation of 10-sec-long LC stimulations. Spectral analysis of the Purkinje cell firing rates (imp./bin, the bin duration was 2-8 sec) for 60- to 120-sec-long intervals was performed using fast Fourier transformation after digital conversion of unitary spikes. Mean power spectra of the Purkinje cell firing rates (derived from 8-sec-long consecutive epochs at a sampling rate of 256 sec-1) showed an increase in the slow frequency range (0.1-1.0 Hz) after LC stimulation, particularly due to the slowest components (below 0.5 Hz). This effect lasted more than 1 min and usually less than 6 min after cessation of LC stimulation and could be interpreted as the development of slow oscillations in the Purkinje cell firing. Our results suggest that slow oscillations of the firing rate of cerebellar output neurons, induced by LC stimulation, reflect a specific coordination of the cerebellar neuronal activities (important for a central norepinephrine influence) in regulation of different pathological states.

Cross-correlation measures of unresolved multi-neuron recordings

An increasing number of laboratories are studying population properties of the nervous system using data where the spike activity of more than one neuron is recorded on each electrode and where, accidentally or deliberately, these activities are not resolved into single unit spike trains. We have previously examined the consequences for measurement of cross-correlation between two such electrodes in the limited case where all individual distant (between electrode) correlations are the same and all individual close (on a single electrode) correlations are the same [Bedenbaugh, P.H., and Gerstein, G.L. (1997). Multiunit normalized cross correlation differs from the average single-unit normalized correlation. Neural Computation 9, 1265–1275]. Here, we lift these unrealistic restrictions to allow all values of individual correlation, and examine explicitly the cases of two or three unresolved neurons on each electrode. In these situations, the cross-correlation coefficient measured between the electrodes is a linear sum of the distant correlations, divided by a non-linear function of the close correlations. We then examine in detail the case of a single direct distant correlation and take account of all relevant indirect correlations. The measured interelectrode correlation shows a reduction of this actual distant correlation by a non-linear function of the close correlations on each electrode over most of their possible values. Finally, we examine the consequences of poor waveform sorting for correlation measures; here a supposedly isolated spike train is contaminated by some fraction of the activity of another train, a situation that unfortunately is all too common in experiments. All these distortions become far more serious in the more realistic situation of dynamic firing rates and correlations. This paper is intended as a cautionary note for those who want to draw inferences about neuronal organization and/or coding or representation by using cross-correlation analysis of unresolved recordings.

Trial-to-Trial Variability and State-Dependent Modulation of Auditory-Evoked Responses in Cortex

Recent experimental work has provided evidence that trial-to-trial variability of sensory-evoked responses in cortex can be explained as a linear superposition of random ongoing background activity and a stationary response. While studying single trial variability and state-dependent modulation of evoked responses in auditory cortex of ketamine/xylazine-anesthetized rats, we have observed an apparent violation of this model. Local field potential and unit spike trains were recorded and analyzed during different anesthesia depths-deep, medium, and light-which were defined by the pattern of ongoing cortical activity. Estimation of single trial evoked response was achieved by considering whole waveforms, rather than just one or two peak values from each wave. Principal components analysis was used to quantitatively classify waveforms on the basis of their time courses (i.e., shapes). We found that not only average response but also response variability is modulated by depth of anesthesia. Trial-to-trial variability is highest under medium levels of anesthesia, during which ongoing cortical activity exhibits rhythmic population bursting activity. By triggering the occurrence of stimuli from the spontaneously occurring burst events, we show that the observed variability can be accounted for by the background activity. In particular, the ongoing activity was found to modulate both amplitude and shape (including latency) of evoked local field potentials and evoked unit activity in a manner not predicted by linear superposition of background activity and a stereotyped evoked response. This breakdown of the linear model is likely attributable to rapid transitions between different levels of thalamocortical excitability (e.g., spike-wave discharges), although brain "state" is relatively fixed.

Detecting symmetric patterns in EEG data: a new method of analysis.

Theoretical models of higher cognitive function predict that cortical activity will exhibit families of spatial-temporal patterns of activity whose individual members are related to each other by specific symmetry transformations. In the trion model, it is suggested that these inherent symmetries play a vital role in how we think and reason. We have developed a method of analysis (SYMMETRIC analysis), which detects families of patterns in EEG data, and characterizes the symmetry relationships between members of those pattern families. Using this analysis, significant symmetry families have been found in EEG and single unit spike train data. If symmetry is a crucial aspect of brain function, it is possible that different pathologies are associated with specific types of symmetry relationships in brain activity that could be detected in EEG data by a SYMMETRIC analysis.

Dynamical cell assemblies in the rat auditory cortex in a reaction-time task

Simultaneous single unit spike trains were recorded in the auditory cortex of freely moving rats performing a complex cognitive task. The experimental paradigm is based on a two-choice task (Go/Nogo) with a two-component (pitch and location) auditory stimulus lasting 500 ms. We report evidence that firstly functional interactions, measured by cross-correlation analysis, between single units in the auditory cortex are dynamically modified in the period preceding the onset of the auditory stimulation, referred to as the ‘waiting period’. We secondly observed that spatio-temporal firing patterns both within, and across cell spike trains also tended to appear in the waiting period, several seconds before the actual stimulus delivery. These patterns indicate a very precise repetition of spike discharges separated by long intervals (up to several hundreds of milliseconds). No consistent changes in mean rate were observed. These results suggest that network activity in the auditory cortex is selectively modified in rate independent ways before the actual sensory stimulation. These modifications may reflect participation of recurrent neuronal networks in processes anticipating the expected sensory input.

Identifying factors that determine kernel number in wheat

Understanding variation in kernel number per unit area (KNO) is of major importance in understanding yield and in identifying opportunities to increase yield potential. Factors that determine KNO should therefore be identified considering wide ranges in both crop and environmental conditions. Several field experiments with various spring wheat cultivars were conducted over three years in Mexico. Wide ranges in crop and environmental conditions were obtained by varying N application rates and timing and by different planting dates and locations. Crop development from emergence (DC10) to physiological maturity (DC90) was divided in three phases, with the intermediate phase II ranging approximately from early booting (DC40) to final anthesis (DC70). A photothermal quotient (PTQ) during phase II failed to explain the variation in KNO. Biomass at anthesis explained 72% of the variance, but could not explain some deviant situations and the relation was strongly cultivar specific. Biomass accumulation during phase II more accurately (80%) explained the deviant situations, except one particular location, and cultivar differences became even more pronounced. At this location KNO was also well explained by non-grain spike weight at a week from anthesis, with a constant number of kernels per unit spike dry matter, while differences among cultivars tended to disappear. Factors that are identified to determine KNO are discussed.

Control of ICP and the cerebrovascular bed by the cholinergic basal forebrain.

The involvement of the cholinergic basal forebrain in the control of ICP and the cerebrovascular bed was investigated by simultaneous measurement of CBF, BP, ICP and ETCO2 in rats and cats. Single unit spikes were also continuously recorded during ICP changes in the dorsomedial hypothalamic nucleus (DMH) of cats. Glutamate or acetylcholine (Ach) microinjection into the magnocellular basal nucleus (nucleus basalis Meynert: NBM, substantia innominata: SI) of rats or the DMH of cats caused persistent increases in ICP associated with slightly decreased BP. Microinjection of Ach into the NBM or the DMH also induced consistent increases in CBF in the cerebral cortex. Spike activities in DMH neurons increased before and during spontaneous ICP elevation. The firing rate of the DMH neurons increased in phase with the plateau wave-like ICP variations elicited by microinjection of Ach into the cholinoceptive pontine area or the contralateral DMH. Glutamate- or Ach-induced increases in ICP resulted from an increased CBV in response to a reduced cerebral vasoconstrictor tone. Activity within the cholinergic basal forebrain, as well as the central noradrenergic system, contribute to ICP changes and may be the intrinsic neuronal origin of the plateau waves occurring in some pathological conditions.

Representation of behaviorally relevant sound frequencies by auditory receptors in the cricket teleogryllus oceanicus

Teleogryllus oceanicus is particularly sensitive to two ranges of sound frequency, one corresponding to intraspecific acoustical signals (4-5 kHz) and the other to the echolocation cries of bats (25-50 kHz). We recorded summed responses of the auditory nerve to stimuli in these two ranges. Nerve responses consist of trains of compound action potentials (CAPs), each produced by the summed activity of a number of receptor neurons. The amplitude of the CAP is up to four times larger for stimuli at 4.5 kHz than for stimuli at 30 kHz, suggesting either that the extracellular spikes produced by receptors that respond to 4.5 kHz are larger than those that respond to 30 kHz, or that receptors fire more synchronously in response to stimulation at 4.5 kHz, or that more receptors respond to stimulation at 4.5 kHz. Neither unit spike amplitude nor conduction velocity (which is expected to vary with spike amplitude) differs for the two frequencies, and the responses to 4.5 kHz are not produced by more tightly synchronized receptor populations, as judged by CAP breadth. We conclude that more receptors respond to 4. 5 kHz than to 30 kHz.

Responses of constantly firing motor units to afferent stimulation.

Constantly firing motor units of the short abductor muscles of the first finger in the human hand and the abdominal wall muscle in immobilized rats responded to afferent stimulation of the median and sciatic nerves respectively with changes in the nature of spike activity. In the first 250 msec of the post-stimulus period, the frequency of motor unit spike activity became unstable and peri-stimulus histograms were individually quite distinct. This was followed by relative stabilization of motor unit discharge frequencies, and the subsequently (750 msec) determined motor unit spike frequency depended on most cases on the background spike frequency.

Multiunit normalized cross correlation differs from the average single-unit normalized correlation.

As the technology for simultaneously recording from many brain locations becomes more available, more and more laboratories are measuring the cross-correlation between single-neuron spike trains, and between composite spike trains derived from several undiscriminated cells recorded on a single electrode (multiunit clusters). The relationship between single-unit correlations and multiunit cluster correlations has not yet been fully explored. We calculated the normalized cross-correlation (NCC) between single-unit spike trains and between small clusters of units recorded in the rat somatosensory cortex. The NCC between small clusters of units was larger than the NCC between single units. To understand this result, we investigated the scaling of the NCC with the number of units in a cluster. Multiunit cross-correlation can be a more sensitive detector of neuronal relationship than single-unit cross-correlation. However, changes in multiunit cross-correlation are difficult to interpret uniquely because they depend on the number of cells recorded on each electrode and because they can arise from changes in the correlation between cells recorded on a single electrode or from changes in the correlation between cells recorded on two electrodes.

Signals and signs in the nervous system: the dynamic anatomy of electrical activity is probably information-rich.

The dichotomy between two groups of workers on neuroelectrical activity is retarding progress. To study the interrelations between neuronal unit spike activity and compound field potentials of cell populations is both unfashionable and technically challenging. Neither of the mutual disparagements is justified: that spikes are to higher functions as the alphabet is to Shakespeare and that slow field potentials are irrelevant epiphenomena. Spikes are not the basis of the neural code but of multiple codes that coexist with nonspike codes. Field potentials are mainly information-rich signs of underlying processes, but sometimes they are also signals for neighboring cells, that is, they exert influence. This paper concerns opportunities for new research with many channels of wide-band (spike and slow wave) recording. A wealth of structure in time and three-dimensional space is different at each scale-micro-, meso-, and macroactivity. The depth of our ignorance is emphasized to underline the opportunities for uncovering new principles. We cannot currently estimate the relative importance of spikes and synaptic communication vs. extrasynaptic graded signals. In spite of a preponderance of literature on the former, we must consider the latter as probably important. We are in a primitive stage of looking at the time series of wide-band voltages in the compound, local field, potentials and of choosing descriptors that discriminate appropriately among brain loci, states (functions), stages (ontogeny, senescence), and taxa (evolution). This is not surprising, since the brains in higher species are surely the most complex systems known. They must be the greatest reservoir of new discoveries in nature. The complexity should not deter us, but a dose of humility can stimulate the flow of imaginative juices.

Synchronization of neurons during local field potential oscillations in sensorimotor cortex of awake monkeys.

1. The neural activity associated with 20- to 40-Hz oscillations in sensorimotor cortex of awake monkeys was investigated by recording action potentials of single and multiple units. At a given site, activity of many units became synchronized with local field potential (LFP) oscillations. Cycle-triggered histograms (CTHs) of unit spikes aligned on cycles of LFP oscillations indicated that about two thirds of the recorded units (n = 268) were entrained with LFP oscillations. On average, units had the highest probability of spiking 2.7 ms before peak LFP negativity, corresponding to a -27.6 degrees phase shift relative to the negative peak of the LFP. 2. The average relative modulation amplitude (RMA), defined as the ratio of amplitude of oscillatory component of CTH and the baseline multiplied by 100, was 45 +/- 27% (mean +/- SD). The RMAs of single units did not differ significantly from those of multiple units. 3. Phase shifts and RMAs did not vary systematically with the cortical depth of recorded units. 4. Autocorrelation histograms (ACHs) of entrained units exhibited clear 20- to 40-Hz periodicity if they were compiled with spikes that occurred during oscillatory episodes in LFPs. ACHs of spikes outside oscillatory episodes usually did not show periodicity. Global ACHs of all spikes typically showed weak or no evidence of periodic activity. 5. Cross-correlation histograms (CCHs) between pairs of units complied with all spikes, whether they occurred during or outside LFP oscillations, seldom revealed significant features (19 of 134 pairs or 14%). However, CCHs compiled with spikes that occurred during oscillatory episodes (OS-CCHs) had significant features in 67 of 134 pairs recorded ipsilaterally; in these 67 cases, units at both sites showed modulation in CTHs. 6. The latencies of the OS-CCH peaks (taking the medial unit as reference) were normally distributed about a mean of -0.5 +/- 13 ms. Normalized peak height of CCHs (peak/baseline x 100) was, on average, 14.3 +/- 11.2%. Peak latency and normalized peak amplitude did not change significantly with horizontal separation of recorded precentral pairs up to 14 mm. 7. Units in the left and right hemispheres could become synchronized during oscillations. Significant features in OS-CCH were detected in 22 of 42 pairs of units recorded bilaterally. The average peak latency was 0.2 +/- 8.0 ms and the average normalized peak amplitude was 10 +/- 8%. These parameters did not differ significantly from those for ipsilateral OS-CCHs. 8. Oscillations tended to affect both the temporal structure and net rate of unit firing. For each unit, the firing rate was clamped to a narrow range of frequencies during oscillatory episodes. The coefficient of variation (SD/mean) of firing rates was significantly reduced during oscillatory episodes compared with prior rates (P < 0.001, paired t-test). However, the overall mean firing rate of each unit during all oscillatory episodes did not differ from its average rate immediately before the episodes. Thus oscillatory episodes tended to clamp mean firing rates to the cells' average rates outside episodes. 9. The strength of synchronization between units during oscillatory episodes was unrelated to their involvement in the task. For pairs of precentral units recorded ipsilaterally, the probability of occurrence of significant features in the OS-CCH was slightly larger when both units of the pair were task related (33 of 56 pairs or 59%) than when only one unit was task related (20 of 39 pairs or 51%) or neither unit was task related (7 of 16 or 44%). However, these differences were not statistically significant. The magnitude of the correlation peak and the latency to peak were also not significantly different for the three cases. 10. These results suggest that units across wide regions can become transiently synchronized specifically during LFP oscillations, even if their spikes are uncorrelated during nonoscillatory periods.

ADAPTATIONS IN MOTOR UNIT FIRING RATES AND CONTRACTILE PROPERTIES AFTER RESISTANCE TRAINING 1220

The purpose of this study was to determine if motor unit firing rates change in parallel with the contractile properties of vastus lateralis following eight weeks of isometric resistance training. The firing rates from more than 400 motor units of vastus lateralis were obtained during voluntary isometric contractions of 50% MVC, before and after training in male subjects(N=10) and their untrained controls (N=10). Single motor unit spike trains were recorded with tungsten microelectrodes. Training resulted in a 36%(p<0.05) increase in MVC. We also found significant increases (p<0.05) in maximal twitch amplitude (+17%), time to peak tension (+9%) and the maximal rate of contraction (+20%) in the trained leg of the experimental group. Neither the maximal integrated EMG nor the rate of increase of integrated EMG was different after training. There were no significant changes in any of these measures from the untrained leg or the control group. Average firing rates were not different after training despite the increase in twitch contractile speed. These findings suggest that the control properties of muscular contraction are not altered despite sizable changes in the contractile properties following eight weeks of resistance training.