Peristimulus Time Histograms Research Articles

Identifying the Source of Radial Nerve Afferents that Inhibit Biceps Brachii

Electrical stimulation of the brachioradialis branch of the radial nerve inhibits the discharge of motor units in biceps brachii. Because the distal portion of brachialis is also innervated by a branch of the radial nerve, however, there is uncertainty over the origin of the inhibitory projection to the motor units in biceps brachii. PURPOSE: To determine the extent to which inhibition of the biceps brachii motor neuron pool with radial nerve stimulation is mediated by afferent projections from the brachioradialis or brachialis. METHODS: Stimulating electrode location was optimized for both the brachioradialis and brachialis branches of the radial nerve by observing the electrically evoked motor responses from the interference electromyogram of both muscles. Six male subjects produced low elbow flexion forces (2.8 ± 1.6 %MVC) to maintain the discharge of a biceps brachii motor unit at 11.1 ±0.8 pps. Stimulation was applied every 2 – 3 s with a 30-ms delay after the discharge of the motor unit. Stimulus intensity was 0.9x motor threshold (MT). Pre- and post-stimulus time histograms were constructed from the 108 ±12 stimuli that occurred during the discharge of the motor units. The influence of the two stimulus locations was assessed on the same biceps brachii motor unit. Inhibition was quantified as the percent change from the pre- to post-stimulus interspike intervals. RESULTS: Seven motor units were recorded for each stimulation location. To determine the selectivity of stimulation, motor thresholds were identified for both muscles at each stimulation site. There was a limited capacity to selectively stimulate either nerve branch; the stimulus intensity (0.9x MT) for each muscle corresponded to ∼0.73x MT for the other muscle. Despite this limited selectivity, the magnitude of inhibition on biceps brachii motor units was significantly less (P <0.05) when stimulation was optimized for the brachialis branch of the radial nerve (3.4 %) than the brachioradialis branch (6.5 %). CONCLUSION: These data suggest that either there are fewer inhibitory afferent projections from radial nerve-innervated brachialis than from brachioradialis or that brachialis afferents do not inhibit biceps brachii motor units and the observed inhibition was due to activation of brachioradialis afferents at a lower stimulus intensity. Inhibition of biceps brachii motor units with radial nerve stimulation appears to be primarily mediated by afferents from the brachioradialis muscle. Supported by NINDS R01 NS43275.

Mediation of late excitation from human hand muscles via parallel group II spinal and group I transcortical pathways

This study addresses the question of the origin of the long-latency responses evoked in flexors in the forearm by afferents from human hand muscles. The effects of electrical stimuli to the ulnar nerve at wrist level were assessed in healthy subjects using post-stimulus time histograms for flexor digitorum superficialis and flexor carpi radialis (FCR) single motor units (eight subjects) and the modulation of the ongoing rectified FCR EMG (19 subjects). Ulnar stimulation evoked four successive peaks of heteronymous excitation that were not produced by purely cutaneous stimuli: a monosynaptic Ia excitation, a second group I excitation attributable to a propriospinally mediated effect, and two late peaks. The first long-latency excitation occurred 8-13 ms after monosynaptic latency and had a high-threshold (1.2-1.5 x motor threshold). When the conditioning stimulation was applied at a more distal site and when the ulnar nerve was cooled, the latency of this late excitation increased more than the latency of monosynaptic Ia excitation. This late response was not evoked in the contralateral FCR of one patient with bilateral corticospinal projections to FCR motoneurones. Finally, oral tizanidine suppressed the long-latency high-threshold excitation but not the early low-threshold group I responses. These results suggest that the late high-threshold response is mediated through a spinal pathway fed by muscle spindle group II afferents. The second long-latency excitation, less frequently observed (but probably underestimated), occurred 16-18 ms after monosynaptic latency, had a low threshold indicating a group I effect, and was not suppressed by tizanidine. It is suggested that this latest excitation involves a transcortical pathway.

Perinatal anoxia degrades auditory system function in rats.

Little is known about the neural bases of the reduced auditory and cortical processing speeds that have been recorded in language-impaired, autistic, schizophrenic, and other disabled human populations. Although there is strong evidence for genetic contributions to etiologies, epigenetic factors such as perinatal anoxia (PA) have been argued to be contributors, or causal, in a significant proportion of cases. In this article, we explored the consequences of PA on this elementary aspect of auditory behavior and on auditory system function in rats that were briefly perinatally anoxic. PA rats had increased acoustic thresholds and reduced processing efficiencies recorded in an auditory behavioral task. These rats had modestly increased interpeak intervals in their auditory brainstem responses, and substantially longer latencies in poststimulus time histogram responses recorded in the primary auditory cortex. The latter were associated with degraded primary auditory cortex receptive fields and a disrupted tonotopy. These processing deficits are consistent with the parallel behavioral and physiological deficits recorded in children and adults with a history of language-learning impairment and autism.

Pinealectomy Reduces Optic Nerve But Not Intergeniculate Leaflet Input to the Suprachiasmatic Nucleus at Night

The suprachiasmatic nucleus (SCN) of the hypothalamus regulates circadian rhythms in mammals. It receives, among others, direct inputs from the retina and from the thalamic intergeniculate leaflet (IGL). The former sends photic signals to the SCN, whereas the latter probably integrates photic and nonphotic information. To characterise these inputs in vivo, extracellular single-unit recordings were made from the SCN of rats under urethane anaesthesia during electrical stimulation of the optic nerve (OptN) or the IGL region. Cell responses were evaluated by creating peri-stimulus time histograms. Because humoral signals such as melatonin might modulate the activity of the SCN in addition to neural inputs, recordings were also made using pinealectomised (Px) rats to test for a possible role of this hormone in regulating inputs to the SCN. A significantly greater number of cells responded to IGL (60 of 90, 67%) than to OptN (35 of 75, 47%) stimulation in intact animals (chi(2) = 5.905, P = 0.015). The same was true when Px animals were tested (IGL, 82 of 131, 63%; OptN, 31 of 111, 28%; chi(2) = 27.637, P < 0.001). In intact animals, the proportion of cells responsive to IGL stimulation during the day and during the night was not significantly different from the proportion responsive in Px animals. The same was true for OptN stimulation during the day. However, during the night, the proportion of cells responsive to OptN stimulation in intact animals was significantly greater than the proportion responsive in Px animals (chi(2) = 7.127, P = 0.008). Our findings suggest that a lack of melatonin modulates OptN but not IGL inputs to the SCN.

Response properties of an integrate-and-fire model that receives subthreshold inputs.

A computational technique is described for calculation of the interspike interval and poststimulus time histograms for the responses of an integrate-and-fire model to arbitrary inputs. The effects of the model parameters on the response statistics were studied systematically. Specifically, the probability distribution of the membrane potential was calculated as a function of time, and the mean interspike interval and PST histogram were calculated for arbitrary inputs. For stationary inputs, the regularity of the output was studied in detail for various model parameters. For nonstationary inputs, the effects of the model parameters on the output synchronization index were explored. The results show that enhanced synchronization in response to low-frequency stimuli required a large number (n > 25) of weak inputs. Irregular responses and a linear input-output rate relationship required strong (but subthreshold) inputs with a small time constant. A model cell with mixed-amplitude synaptic inputs can respond to stationary inputs irregularly and have enhanced synchronization to nonstationary inputs that are phase-locked to low-frequency inputs. Both of these response properties have been reported for some cells in the ventral cochlear nucleus in the auditory brainstem.

A Functional Point-Neuron Model Simulating Cochlear Nucleus Ideal Onset Responses

Cochlear nucleus neurons revealing ideal onset (OI)-type peri-stimulus time histograms (PSTH) encode temporal features of acoustic stimuli with very high precision. These neurons are therefore assumed to be involved in the recognition of natural sounds with temporally varying envelopes such as speech. A functional point-neuron model is presented here for the simulation of OI-unit responses found in cochlear nucleus octopus cells. The model assumes a biphasic response of the membrane potential to a current impulse, the membrane impulse response, and a dynamic spike-blocking mechanism. The predicted responses to pure tones at low and high frequencies, injected current steps, and amplitude modulated tones are compared to recordings from the literature. The model accounts for the main response properties in the data using the same small set of parameters for all experimental conditions. The assumed biphasic shape of the membrane impulse response, reflecting a higher sensitivity to stimulus transients and fast changes relative to sustained stimulus portions, allows for a description of OI-unit responses that cannot be accounted for by a coincidence detector model with an integrate-to-threshold dynamic. The presented functional model may be useful as a processing module in more complex models of auditory signal processing and perception.

Statistical Assessment of Time-Varying Dependency Between Two Neurons

The joint peristimulus time histogram (JPSTH) provides a visual representation of the dynamics of correlated activity for a pair of neurons. There are many ways to adjust the JPSTH for the time-varying firing-rate modulation of each neuron, and then to define a suitable measure of time-varying correlated activity. Our approach is to introduce a statistical model for the time-varying joint spiking activity so that the joint firing rate can be estimated more efficiently. We have applied an adaptive smoothing method, which has been shown to be effective in capturing sudden changes in firing rate, to the ratio of joint firing probability to the probability of firing predicted by independence. A bootstrap procedure, applicable to both Poisson and non-Poisson data, was used to define a statistical significance test of whether a large ratio could be attributable to chance alone. A numerical simulation showed that the bootstrap-based significance test has very nearly the correct rejection probability, and can have markedly better power to detect departures from independence than does an approach based on testing contiguous bins in the JPSTH. In a companion paper, we show how this formulation can accommodate latency and time-varying excitability effects, which can confound spike timing effects.

Trial-to-Trial Variability and Its Effect on Time-Varying Dependency Between Two Neurons

The joint peristimulus time histogram (JPSTH) and cross-correlogram provide a visual representation of correlated activity for a pair of neurons, and the way this activity may increase or decrease over time. In a companion paper we showed how a Bootstrap evaluation of the peaks in the smoothed diagonals of the JPSTH may be used to establish the likely validity of apparent time-varying correlation. As noted in earlier studies by Brody and Ben-Shaul et al., trial-to-trial variation can confound correlation and synchrony effects. In this paper we elaborate on that observation, and present a method of estimating the time-dependent trial-to-trial variation in spike trains that may exceed the natural variation displayed by Poisson and non-Poisson point processes. The statistical problem is somewhat subtle because relatively few spikes per trial are available for estimating a firing-rate function that fluctuates over time. The method developed here decomposes the spike-train variability into a stimulus-related component and a trial-specific component, allowing many degrees of freedom to characterize the former while assuming a small number suffices to characterize the latter. The Bootstrap significance test of the companion paper is then modified to accommodate these general excitability effects. This methodology allows an investigator to assess whether excitability effects are constant or time-varying, and whether they are shared by two neurons. In data from two V1 neurons we find that highly statistically significant evidence of dependency disappears after adjustment for time-varying trial-to-trial variation.

The disynaptic group I inhibition between wrist flexor and extensor muscles revisited in humans

The present studies are designed to further characterise the interneuronal pathway mediating the disynaptic reciprocal group I inhibition between flexors and extensors at the wrist and the elbow levels in humans. In the first series of experiments, we compared the electrical threshold of the reciprocal group I inhibition at the wrist and the elbow level after a prolonged vibration aimed at raising the electrical threshold of the antagonistic activated Ia afferents. Prolonged vibration to the 'conditioning' tendon, which raised significantly the electrical threshold of the inhibition at the elbow level, did not alter it at the wrist level. These results suggest that the dominant input to the relevant interneurones is Ia in origin at the elbow level but Ib in origin at the wrist level. In the second series of experiments, using the spatial facilitation method, we compared the effects on the post-stimulus time histograms of single voluntarily activated motor units of two volleys delivered both separately and together to group I afferents in the nerves supplying the homonymous and antagonistic muscles. At the wrist, but not at the elbow level, the peak of homonymous monosynaptic group I excitation was reduced on combined stimulation, although the antagonistic IPSP was just at the threshold. Because the suppression did not involve the initial bins of the peak, it is argued that the suppression is not due to presynaptic inhibition of Ia terminals, but probably reflects convergence between the homonymous and antagonistic volleys onto the interneurones mediating the disynaptic inhibition. Taken together with the previously reported effects of recurrent inhibition on reciprocal inhibition, these results suggest that inhibition between flexors and extensors is differently organised at the elbow (reciprocal Ia inhibition) and the wrist (non-reciprocal group I inhibition) levels. It is argued that the particular connectivity at the wrist level might correspond to some functional requirements at this ball joint.

A microelectrode array (MEA) integrated with clustering structures for investigating in vitro neurodynamics in confined interconnected sub-populations of neurons

Understanding how the information is coded in large neuronal networks is one of the major challenges for neuroscience. A possible approach to investigate the information processing capabilities of the neuronal ensembles is given by the use of dissociated neuronal cultures coupled to microelectrode arrays (MEAs). Here, we describe a new strategy, based on MEAs, for studying in vitro neuronal network dynamics in interconnected sub-populations of cortical neurons. The rationale is to sub-divide the neuronal network into communicating clusters while preserving a high degree of functional connectivity within each confined sub-population, i.e. to achieve a compromise between a completely random large neuronal population and a patterned network, such as currently used with conventional MEAs. To this end, we have realized and functionally characterized a Pt microelectrode array with an integrated EPON SU-8 clustering structure, allowing to confine five relatively large yet interconnected spontaneously developing neuronal networks (i.e. thousands of cells). The clustering structure consists of five chambers of 3 mm in diameter interconnected via 800 μm long and 300 μm wide microchannels and is integrated on the MEA of 60 thin-film Pt electrodes of 30 μm diameter. Tests of the Pt microelectrodes’ stability under stimulation showed a stable behavior up to 35,000 voltage stimuli and the biocompatibility was assessed with the cultures of dissociated rat's cortical neurons achieving cultures’ viability up to 60 days in vitro. Compared to conventional MEAs, the monitoring of spontaneous and evoked activity and the computation of the Post-Stimulus Time Histogram (PSTH) within the clusters clearly demonstrates: (i) the capability to selectively activate (through poly-synaptic pathways) specific network regions and (ii) the confinement of the network dynamics mainly in the highly connected sub-networks.

Phase-Response Curves Give the Responses of Neurons to Transient Inputs

Neuronal firing is determined largely by incoming barrages of excitatory postsynaptic potentials (EPSPs), each of which produce a transient increase in firing probability. To measure the effects of weak transient inputs on firing probability of cortical neurons, we compute phase-response curves (PRCs). PRCs, whose shape can be related to the dynamics of spike generation, document the changes in timing of spikes caused by an EPSP in a repetitively firing neuron as a function of when it arrives in the interspike interval (ISI). The PRC can be exactly related to the poststimulus time histogram (PSTH) so that knowledge of one uniquely determines the other. Typically, PRCs have zero values at the start and end of the ISI, where EPSPs have minimal effects and a peak in the middle. Where the peak occurs depends in part on the firing properties of neurons. The PRC can have regions of positivity and negativity corresponding respectively to speeding up and slowing down the time of the next spike. A simple canonical model for spike generation is introduced that shows how both the background firing rate and the degree of postspike afterhyperpolarization contribute to the shape of the PRC and thus to the PSTH. PRCs in strongly adapting neurons are highly skewed to the right (indicating a higher change in probability when the EPSPs appear late in the ISI) and can have negative regions (indicating a decrease in firing probability) early in the ISI. The PRC becomes more skewed to the right as the firing rate decreases. Thus at low firing rates, the spikes are triggered preferentially by inputs that occur only during a small time interval late in the ISI. This implies that the neuron is more of a coincidence detector at low firing frequencies and more of an integrator at high frequencies. The steady-state theory is shown to also hold for slowly varying inputs.

Does Neuronal Synchrony Underlie Visual Feature Grouping?

Previous research suggests that synchronous neural activity underlies perceptual grouping of visual image features. The generality of this mechanism is unclear, however, as previous studies have focused on pairs of neurons with overlapping or collinear receptive fields. By sampling more broadly and employing stimuli that contain partially occluded objects, we have conducted a more incisive test of the binding by synchrony hypothesis in area MT. We find that synchrony in spiking activity shows little dependence on feature grouping, whereas gamma band synchrony in field potentials can be significantly stronger when features are grouped. However, these changes in gamma band synchrony are small relative to the variability of synchrony across recording sites and do not provide a robust population signal for feature grouping. Moreover, these effects are reduced when stimulus differences nearby the receptive fields are eliminated using partial occlusion. Our findings suggest that synchrony does not constitute a general mechanism of visual feature binding.

State-Dependent Sensory Gating in Olfactory Cortex

Sensory systems show behavioral state-dependent gating of information flow that largely depends on the thalamus. Here we examined whether the state-dependent gating occurs in the central olfactory pathway that lacks a thalamic relay. In urethane-anesthetized rats, neocortical EEG showed a periodical alternation between two states: a slow-wave state (SWS) characterized by large and slow waves and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings from olfactory cortex neurons showed robust spike responses to adequate odorants during FWS, whereas they showed only weak responses during SWS. The state-dependent change in odorant-evoked responses was observed in a majority of olfactory cortex neurons, but in only a small percentage of olfactory bulb neurons. These findings demonstrate a powerful state-dependent gating of odor information in the olfactory cortex that works in synchrony with the gating of other sensory systems. They suggest a state-dependent switchover of signal processing modes in the olfactory cortex.

Auditory nerve representation of naturally-produced vowels with variable acoustics

This investigation compared the encoding of naturally-produced, whispered and normally-voiced vowels by auditory nerve fibers. Speech syllables containing the vowels /ɔ/ and /æ/ were produced by two female speakers and presented at three intensities to ketamine-anesthetized chinchillas. Six different representations of the spectral components in the vowels in the responses of the auditory nerve fibers were evaluated. For both normal and whispered vowels over a 30 dB range, the formant peaks in the vowel were best displayed using rate–place representations. The spectral detail in the vowel was revealed by average localized synchronized rates (ALSR) and autocorrelations of individual peristimulus time histograms. The average localized interval rates (ALIR), autocorrelations of ensemble responses, and autocorrelations of individual spike trains demonstrated poor representations of vowel spectra, although the frequency components of normally-voiced vowels had better representations than those of whispered vowels. These analyses suggest that rate-based and synchronization-based measures yields two very different pieces of information, but only a normalized rate-based measure consistently identified the formants of both the whispered and normally-voiced vowels.

The influence of contraction amplitude and firing history on spike‐triggered averaged trapezius motor unit potentials

The spike-triggered averaged (STA) technique was used to examine trapezius motor unit potentials and their dependence on contraction amplitude and firing history. Individual motor unit firings were identified by a fine-wire intramuscular electrode, while STA-derived potentials were extracted from the simultaneously recorded surface electromyographic (SEMG) signal. Amplitude-controlled contractions and contractions with typing tasks and mental stress were carried out. STA potentials were mostly derived from 20 s intervals of firing. Motor unit synchrony was estimated by peristimulus time histograms (PSTHs). An association between SEMG amplitude and STA-derived motor unit potentials was found: motor unit area showed a four-fold increase when SEMG amplitude increased from 1.5 to 10.5% of the root mean square-detected SEMG signal at maximal voluntary contraction (%EMG(max)). Low- and higher threshold motor unit potentials, all with recruitment thresholds <10% EMG(max), had similar area at the same contraction amplitude. A significant increase in the STA-derived potentials was observed after 3 min of constant-amplitude contractions; however, this difference was reduced after 10 min and no longer present after 30 min of contraction. Motor unit synchrony accounted for, on average, 2.8% additional firings within 2 ms of the triggering motor unit. We conclude that the increase in STA-derived potentials with contraction amplitude is, to a major extent, due to motor unit synchrony, limiting the applicability of this method in postural muscles presenting wide motor unit potentials. The similar area of motor units at same SEMG amplitude may indicate that trapezius motor units recruited below 10% EMG(max) are of similar size and thus not organized according to the Henneman size principle.

Hazard Functions and Expected Spike Density Functions for Neuron Spike Activity in the Cochlear Nucleus of the Cat

The goal of these experiments was to evaluate the effect of stimulus evoked input and post spike refractoriness on the shapes of post stimulus time histograms (PSTHs). The time courses of spontaneous and/or evoked activity were studied in 153 neurons located predominantly in the dorsal cochlear nucleus in cats anesthetized with Nembutal. Tone bursts were presented to the ipsilateral ear in a free sound field. About half the cells were characterized by the pauser/build-up type of PSTH. Marked refractoriness was evidenced by relatively long recovery times of the hazard functions of spontaneous and tone-evoked spike activity. On presentation of tonal bursts, the time dependence of the probability of the first spike in the absence of a preceding spike (expected spike density function) was greater than the PSTH (actual spike density function). The initial PSTH peak with pause was shaped primarily by stimulus evoked input, whereas refractoriness tended to diminish the build-up portion of the PSTH. In chopper cells, PSTH peaks were usually not reflected in expected spike density functions showing that post spike refractoriness plays a major role in shaping the PSTH. In primary-like cells, refractoriness was small and had little effect on the shape of the PSTH. Some presumptively inhibitory cells showed a tendency to burst discharges with non-monotonic hazard functions. A very small number of cells showed a tendency to internal tuning to a defined signal periodicity.

Effects of age on latency and variability of visual response in monkeys

Visual function declines during normal aging. The neural mechanisms underlying age-related changes have just begun to be revealed. It has been demonstrated that retinal ganglion cells and cells in dorsal lateral geniculate nucleus (dLGN) in old monkeys are relatively normal. However, age-related functional degradations have been found at cellular level in mammalian visual cortex. Decreased orientation and direction selectivity of neurons in primary visual cortex (V1) have been reported in both aged monkeys and cats. Similar degradation of stimulus selectivity also occurs in secondary visual cortex (V2) in old monkeys. In addition, we have reported prolonged response latency in both V1 and V2 of old primates. Response latency of neuron can be affected by several factors, including conduction speed of the axons, synaptic integration, action potential initiation and the response variability. These factors may all contribute to delayed visual response in aged animals. For example, increased response variability will affect the temporal integration in synaptic transmission, resulting in prolonged response latency in the postsynaptic neurons. On the other hand, the evaluation of latency depends on the reproducibility of response. The more variable the spike train driven by external stimulus, the longer time will be needed to reach the peak in the post-stimulus time histogram (PSTH). Thus, a prolonged latency will be observed. In the present experiment, using monkeys in early stage of senescence as subjects, we studied the effects of age on response variability and its relationship with the prolonged latency, aiming to investigate possible neural mechanisms underlying the age-related alteration of response latency. Subjects for this study were 3 young adult (5―6 years old) and 3 old (21―22 years old) male rhesus monkeys (Macaca mullata). All experimental protocols were consistent with the guidelines of the Society for Neuroscience and National Institute of Health. Monkeys were examined ophthalmoscopically to ensure that they had no optical or retinal problems that would impair visual function. Conventional acute extracellcular single unit recording technique was used to record the activity of V1 neurons of anaesthetized and paralyzed monkeys. The receptive field properties of neurons were analyzed as described previously. Visual stimuli were presented on a tangent screen positioned 171 cm from the retina (3 cm corresponds to 1° of visual angle). The visual stimulus was a flashing square within receptive field with optimal size for each cell, which is commonly used in related studies. The luminance of the stimulus used was 12.3 cd/m for white and 0.95 cd/m for black. For each cell, we presented the identical visual stimulus for 50 times, with an ON period of 0.5 s and an OFF period of 3 s, and accumulated a PSTH that represents the probability of firing as a function of time. The neurons with low response variability fire at almost the same time in 50 presentations, resulting in a sharp rising branch in PSTH. In contrast, the neurons with high response variability will produce a peak with a relative flat rising branch. Then, the rising branch of the first peak in PSTH with an amplitude equal or larger than three times of spontaneous activity was fitted by a Gaussian curve (y=y0+Aexp(-((x-x0)/ ) ) whose half-width ( ) was taken as a measure of the trial-to-trial variability, and time offset (x0) as the response latency (Peak latency). We studied the visual responses of 90 V1 cells in young monkeys and 99 V1 cells in old monkeys. Fig. 1 represents four typical PSTHs. The cells recorded in aged animals showed significant prolonged response latencies and increasing response variabilities, compared with cells in young monkeys (Table 1, Fig. 2(a), (b)). The finding of prolonged latency in aged animals is consistent with our previous study. However, the subjects we used in the present experiment were 21―22 years old monkeys, while the monkeys in our previous study were 28―32 years old. Analysis based on the sex maturation and lifespan revealed that the degree of senescence of 21―22 years old monkeys approximately equals 60―70 years old human beings, and 28―32 years old monkeys correspond to 80―90 years old human beings. The present results have demonstrated that the prolonged response latency occurs during the early stage of aging. It provided possible neural mechanisms underlying the delay in visual signal analysis and slowness of reaction time for visual stimulus in old people. The average for young monkey cells was 2.82 ms. In comparison, V1 cells in aged monkeys showed significant increased value of (4.56 ms), suggesting higher variability of response. The increase in re

Convergence of auditory-nerve fiber projections onto globular bushy cells

Globular bushy cells are a key element of brainstem circuits that mediate the early stages of sound localization. Many of their physiological properties have been attributed to convergence of inputs from the auditory nerve, many of which are large with complex geometry, but the number of these terminals contacting individual cells has not been measured directly. Herein we report, using cats as the experimental model, that this number ranged greatly (9–69) across a population of 12 cells, but over one-half of the cells (seven of 12) received between 15 and 23 inputs. In addition, we provide the first measurements of cell body surface area, which also varies considerably within this population and is uncorrelated with convergence. For one cell, we were able to document axonal structure over a distance greater than 100μm, between the soma and the location where the axon expanded to its characteristic large diameter. These data were combined with accumulated physiological information on vesicle release, receptor kinetics and voltage-gated ionic conductances, and incorporated into computational models for four cells that are representative of the structural variation within our sample population. This predictive model reveals that basic physiological features, such as precise first spike latencies and peristimulus time histogram shapes, including primary-like with notch and onset-L, can be generated in these cells without including inhibitory inputs. However, phase-locking is not significantly enhanced over auditory-nerve fibers. These combined anatomical and computational approaches reveal additional parameters, such as active zone density, nerve terminal size, numbers and sources of inhibitory inputs and their activity patterns, that must be determined and incorporated into next-generation models to understand the physiology of globular bushy cells.

Spectral representation—analyzing single-unit activity in extracellularly recorded neuronal data without spike sorting

One step in the conventional analysis of extracellularly recorded neuronal data is spike sorting, which separates electrical signal into action potentials from different neurons. Because spike sorting involves human judgment, it can be subjective and time intensive, particularly for large sets of neurons. Here we propose a simple, automated way to construct alternative representations of neuronal activity, called spectral representation (SR). In this approach, neuronal spikes are mapped to a discrete space of spike waveform features and time. Spectral representation enables us to find single-unit stimulus-related changes in neuronal activity without spike sorting. We tested the ability of this method to predict stimuli using both simulated data and experimental data from an auditory mapping study in anesthetized marmoset monkeys. We find that our approach produces more accurate classification of stimuli than spike-sorted data for both simulated and experimental conditions. Furthermore, this method lends itself to automated analysis of extracellularly recorded neuronal ensembles. Additionally, we suggest ways in which these representations can be readily extended to assist in spike sorting and the evaluation of single-neuron peri-stimulus time histograms.

Applications of random field theory to electrophysiology

The analysis of electrophysiological data often produces results that are continuous in one or more dimensions, e.g., time–frequency maps, peri-stimulus time histograms, and cross-correlation functions. Classical inferences made on the ensuing statistical maps must control family wise error (FWE) when searching across the map's dimensions. In this paper, we borrow multiple comparisons procedures, established in neuroimaging, and apply them to electrophysiological data. These procedures use random field theory (RFT) to adjust p-values from statistics that are functions of time and/or frequency. This RFT adjustment for continuous statistical processes plays the same role as a Bonnferonni adjustment in the context of discrete statistical tests. Here, by analysing the time–frequency decompositions of single channel EEG data we show that RFT adjustments can be used in the analysis of electrophysiological data and illustrate the advantages of this method over existing approaches.