First-spike Latency Research Articles

The Sparseness of Neuronal Responses in Ferret Primary Visual Cortex

Various arguments suggest that neuronal coding of natural sensory stimuli should be sparse (i.e., individual neurons should respond rarely but should respond reliably). We examined sparseness of visual cortical neurons in anesthetized ferret to flashed natural scenes. Response behavior differed widely between neurons. The median firing rate of 4.1 impulses per second was slightly higher than predicted from consideration of metabolic load. Thirteen percent of neurons (12 of 89) responded to <5% of the images, but one-half responded to >25% of images. Multivariate analysis of the range of sparseness values showed that 67% of the variance was accounted for by differing response patterns to moving gratings. Repeat presentation of images showed that response variance for natural images exaggerated sparseness measures; variance was scaled with mean response, but with a lower Fano factor than for the responses to moving gratings. This response variability and the "soft" sparse responses (Rehn and Sommer, 2007) raise the question of what constitutes a reliable neuronal response and imply parallel signaling by multiple neurons. We investigated whether the temporal structure of responses might be reliable enough to give additional information about natural scenes. Poststimulus time histogram shape was similar for "strong" and "weak" stimuli, with no systematic change in first-spike latency with stimulus strength. The variance of first-spike latency for repeat presentations of the same image was greater than the latency variance between images. In general, responses to flashed natural scenes do not seem compatible with a sparse encoding in which neurons fire rarely but reliably.

Synaptic Ribbon Enables Temporal Precision of Hair Cell Afferent Synapse by Increasing the Number of Readily Releasable Vesicles: A Modeling Study

Synaptic ribbons are classically associated with mediating indefatigable neurotransmitter release by sensory neurons that encode persistent stimuli. Yet when hair cells lack anchored ribbons, the temporal precision of vesicle fusion and auditory nerve discharges are degraded. A rarified statistical model predicted increasing precision of first-exocytosis latency with the number of readily releasable vesicles. We developed an experimentally constrained biophysical model to test the hypothesis that ribbons enable temporally precise exocytosis by increasing the readily releasable pool size. Simulations of calcium influx, buffered calcium diffusion, and synaptic vesicle exocytosis were stochastic (Monte Carlo) and yielded spatiotemporal distributions of vesicle fusion consistent with experimental measurements of exocytosis magnitude and first-spike latency of nerve fibers. No single vesicle could drive the auditory nerve with requisite precision, indicating a requirement for multiple readily releasable vesicles. However, plasmalemma-docked vesicles alone did not account for the nerve's precision--the synaptic ribbon was required to retain a pool of readily releasable vesicles sufficiently large to statistically ensure first-exocytosis latency was both short and reproducible. The model predicted that at least 16 readily releasable vesicles were necessary to match the nerve's precision and provided insight into interspecies differences in synaptic anatomy and physiology. We confirmed that ribbon-associated vesicles were required in disparate calcium buffer conditions, irrespective of the number of vesicles required to trigger an action potential. We conclude that one of the simplest functions ascribable to the ribbon--the ability to hold docked vesicles at an active zone--accounts for the synapse's temporal precision.

Cues for Sound Localization Are Encoded in Multiple Aspects of Spike Trains in the Inferior Colliculus

To localize sound, information from three cues--interaural timing differences (ITDs), interaural level differences (ILDs), and spectral notch cues (SNs)--must be properly integrated. The inferior colliculus (IC) receives convergent input from neurons encoding all three cues. Using virtual space stimuli and information theoretic techniques, we investigated the coding of the various localization cues in single neurons of the IC under different encoding schemes. Here we focus on the analysis of information encoded by first-spike latency, in comparison to previous results on discharge rate and ongoing spike timing. The results show that the localization cues converge to different degrees in particular neurons. ITD information is conveyed most strongly by spike rate, with small amounts of independent information in latency and ongoing spike timing. ILD information shows a similar pattern, with larger mutual information values for all three cues. For these cues, ongoing spike timing does not typically contribute independent information over that captured by a joint rate/first-spike latency code. SNs are coded by both rate and first-spike latency, but ongoing spike timing significantly enhances their representation in a best frequency-dependent manner, as long as the temporal envelope of the stimulus can be used in the decoder. The differential coding of the localization cues suggests that information about multiple cues could be multiplexed onto the responses of single neurons.

Changes Across Time in the Temporal Responses of Auditory Nerve Fibers Stimulated by Electric Pulse Trains

Most auditory prostheses use modulated electric pulse trains to excite the auditory nerve. There are, however, scant data regarding the effects of pulse trains on auditory nerve fiber (ANF) responses across the duration of such stimuli. We examined how temporal ANF properties changed with level and pulse rate across 300-ms pulse trains. Four measures were examined: (1) first-spike latency, (2) interspike interval (ISI), (3) vector strength (VS), and (4) Fano factor (FF, an index of the temporal variability of responsiveness). Data were obtained using 250-, 1,000-, and 5,000-pulse/s stimuli. First-spike latency decreased with increasing spike rate, with relatively small decrements observed for 5,000-pulse/s trains, presumably reflecting integration. ISIs to low-rate (250 pulse/s) trains were strongly locked to the stimuli, whereas ISIs evoked with 5,000-pulse/s trains were dominated by refractory and adaptation effects. Across time, VS decreased for low-rate trains but not for 5,000-pulse/s stimuli. At relatively high spike rates (>200 spike/s), VS values for 5,000-pulse/s trains were lower than those obtained with 250-pulse/s stimuli (even after accounting for the smaller periods of the 5,000-pulse/s stimuli), indicating a desynchronizing effect of high-rate stimuli. FF measures also indicated a desynchronizing effect of high-rate trains. Across a wide range of response rates, FF underwent relatively fast increases (i.e., within 100 ms) for 5,000-pulse/s stimuli. With a few exceptions, ISI, VS, and FF measures approached asymptotic values within the 300-ms duration of the low- and high-rate trains. These findings may have implications for designs of cochlear implant stimulus protocols, understanding electrically evoked compound action potentials, and interpretation of neural measures obtained at central nuclei, which depend on understanding the output of the auditory nerve.

Influence of Inhibitory Inputs on Rate and Timing of Responses in the Anteroventral Cochlear Nucleus

Anatomical and physiological studies have shown that anteroventral cochlear nucleus (AVCN) neurons receive glycinergic and GABAergic inhibitory inputs. In this study, changes in the temporal responses of AVCN neurons to pure tones and complex sounds after blocking inhibition were analyzed. Blocking inhibition influenced the temporal responses of each type of AVCN neuron. Choppers showed more chopping peaks and shortened chopping cycles after blocking inhibition. Sustained and slowly adapting choppers showed increased regularity throughout the response duration after blocking inhibition, whereas most transient choppers showed increased regularity in the early part of the response. Diverse changes in temporal response patterns were observed in neurons with primary-like and unusual responses, with several neurons showing a large decrease in the first-spike latency after blocking inhibition. This result disagreed with previous findings that onset responses are less affected than sustained responses by manipulating inhibition. Although blocking inhibition had a greater effect on spontaneous activity than that on tone-evoked activity, the change in spontaneous activity was less significant because of larger variability. In addition, for relatively high level masker noises, blocking inhibition had similar effects on responses to noise-alone and noise-plus-tone stimuli, in contrast with previous studies with low-level background noise. In general, inhibition had an enhancing effect on temporal contrast only for responses to amplitude-modulated tones, for which envelope synchrony was enhanced. Results of this study contribute new information about the characteristics, functional roles, and possible sources of inhibitory inputs received by AVCN neurons.

Towards a unifying basis of auditory thresholds: Distributions of the first-spike latencies of auditory-nerve fibers

Detecting sounds in quiet is the simplest task performed by the auditory system, but the neural mechanisms underlying perceptual detection thresholds for sounds in quiet are still not understood. Heil and Neubauer [Heil, P., Neubauer, H., 2003. A unifying basis of auditory thresholds based on temporal summation. Proc. Natl. Acad. Sci. USA 100, 6151–6156] have provided evidence for a simple probabilistic model according to which the stimulus, at any point in time, has a certain probability of exceeding threshold and being detected. Consequently, as stimulus duration increases, the cumulative probability of detection events increases, performance improves, and threshold amplitude decreases. The origin of these processes was traced to the first synapse in the auditory system, between the inner hair cell and the afferent auditory-nerve fiber (ANF). Here we provide further support for this probabilistic “continuous-look” model. It is derived from analyses of the distributions of the latencies of the first spikes of cat ANFs with very low spontaneous discharge rates to tones of different amplitudes. The first spikes in these fibers can be considered detection events. We show that, as predicted, the distributions can be explained by the joint probability of the occurrence of three independent sub-events, where the probability of each of those occurring is proportional to the low-pass filtered stimulus amplitude. The “temporal integration” functions of individual ANFs, derived from their first-spike latencies, are remarkably similar in shape to “temporal integration” functions, which relate threshold sound pressure level at the perceptual level to stimulus duration. This further supports a close link between the mechanisms determining the timing of the first (and other) evoked spikes at the level of the auditory nerve and detection thresholds at the perceptual level. The possible origin and some functional consequences of the expansive power-law non-linearity are discussed.

First spike latency and spike count as functions of tone amplitude and frequency in the inferior colliculus of mice

Spike counts (SC) or, spike rate and first spike latency (FSL), are both used to evaluate the responses of neurons to amplitudes and frequencies of acoustic stimuli. However, it is unclear which one is more suitable as a parameter for evaluating the responses of neurons to acoustic amplitudes and frequencies, since systematic comparisons between SC and FSL tuned to different amplitudes and frequencies, are scarce. This study systematically compared the precision and stability (i.e., the resolution and the coefficient variation, CV) of SC- and FSL-function as frequencies and amplitudes in the inferior colliculus of mice. The results showed that: (1) the SC-amplitude functions were of diverse shape (monotonic, nonmonotonic and saturated) whereas the FSL-amplitude functions were in close registration, in which FSL decreased with the increase of amplitude and no paradoxical (an increase in FSL with increasing amplitude) or constant (an independence of FSL on amplitude) neuron was observed; (2) the discriminability (resolution) of differences in amplitude and frequency based on FSL are higher than those based on SC; (3) the CVs of FSL for low amplitude stimuli were smaller than those of SC; (4) the fraction of neurons for which BF = CF (within ±500 Hz) obtained from FSL was higher than that from SC at any amplitude of sound. Therefore, SC and FSL may vary, independent from each other and represent different parameters of an acoustic stimulus, but FSL with its precision and stability appears to be a better parameter than SC in evaluation of the response of a neuron to frequency and amplitude in mouse inferior colliculus.

A physiological model for the stimulus dependence of first-spike latency of auditory-nerve fibers

Recent studies have shown a close correspondence between perceptual detection thresholds for sounds in quiet and a measure of neuronal thresholds derived from the stimulus-dependent timing of the first spike of auditory-nerve fibers. In addition, stimulus properties might be encoded by differences in first-spike timing of neurons in the central auditory system. Therefore, the physiological mechanisms underlying first-spike timing are of considerable interest, but are not thoroughly understood. Here, we present a physiological model which accurately explains the observed stimulus dependence of the first-spike latency of auditory-nerve fibers with a minimum number of physiologically plausible parameters. Two of the 5 parameters can be considered constant (at least for the vast majority of fibers), while the other 3 vary in meaningful ways with the fibers' spontaneous discharge rates. The elements of the model and some implications are discussed.

Activation of the serotonin 1A receptor alters the temporal characteristics of auditory responses in the inferior colliculus

Serotonin, like other neuromodulators, acts on a range of receptor types, but its effects also depend on the functional characteristics of the neurons responding to receptor activation. In the inferior colliculus (IC), an auditory midbrain nucleus, activation of a common serotonin (5-HT) receptor type, the 5-HT 1A receptor, depresses auditory-evoked responses in many neurons. Whether these effects occur differentially in different types of neurons is unknown. In the current study, the effects of iontophoretic application of the 5-HT 1A agonist 8-OH-DPAT on auditory responses were compared with the characteristic frequencies (CFs), recording depths, and control first-spike latencies of the same group of IC neurons. The 8-OH-DPAT-evoked change in response significantly correlated with first-spike latency across the population, so that response depressions were more prevalent in longer-latency neurons. The 8-OH-DPAT-evoked change in response did not correlate with CF or with recording depth. 8-OH-DPAT also altered the temporal characteristics of spike trains in a subset of neurons that fired multiple spikes in response to brief stimuli. For these neurons, activation of the 5-HT 1A receptor suppressed lagging spikes proportionally more than initial spikes. These results suggest that the 5-HT 1A receptor, by affecting the timing of the responses of both individual neurons and the neuron population, shifts the temporal profile of evoked activity within the IC.

Heterogeneous Biophysical Properties of Frog Dorsal Medullary Nucleus (Cochlear Nucleus) Neurons

The cochlear nucleus (CN) in mammals, or its counterpart in birds, has multiple subdivisions each containing distinct morphological and functional (i.e., temporal discharge patterns and biophysical properties) cell types that project to different auditory nuclei in the brain stem in parallel. The analogous structure in frogs, the dorsal medullary nucleus (DMN), is a single phylogenetically older structure with no subdivision. Similar to the CN, the DMN has complex cytoarchitecture and contains neurons with diverse morphological phenotypes, but whether these cell types possess distinct biophysical characteristics, like their counterparts in mammals and avians, is unclear. Here we show that DMN neurons in young adult northern leopard frogs (Rana pipiens pipiens) possess heterogeneous biophysical properties. There are four major biophysical phenotypes on the basis of the unit's response (i.e., its temporal firing pattern) to depolarizing currents: onset, phasic-burst, sustained-chopper, and adapting. These cells have distinct membrane input resistances and time constants, spike shapes, current-voltage relationships, first-spike latencies, entrainment characteristics, and ionic compositions (i.e., low-threshold potassium current, I(kl), and hyperpolarization-activated current, I(h)). Furthermore, these phenotypes correspond to cells' dendritic morphologies, and they bear similarities and differences to those found in the mammalian CN. The similarities are remarkable considering that amphibians are a distinct evolutionary lineage from birds and mammals.

Latency represents sound frequency in mouse IC

Frequency is one of the fundamental parameters of sound. The frequency of an acoustic stimulus can be represented by a neural response such as spike rate, and/or first spike latency (FSL) of a given neuron. The spike rates/frequency function of most neurons changes with different acoustic amplitudes, whereas FSL/frequency function is highly stable. This implies that FSL might represent the frequency of a sound stimulus more efficiently than spike rate. This study involved representations of acoustic frequency by spike rate and FSL of central inferior colliculus (IC) neurons responding to free-field pure-tone stimuli. We found that the FSLs of neurons responding to characteristic frequency (CF) of sound stimulus were usually the shortest, regardless of sound intensity, and that spike rates of most neurons showed a variety of function according to sound frequency, especially at high intensities. These results strongly suggest that FSL of auditory IC neurons can represent sound frequency more precisely than spike rate.

First-spike latency information in single neurons increases when referenced to population onset

It is well known that many stimulus parameters, such as sound location in the auditory system or contrast in the visual system, can modulate the timing of the first spike in sensory neurons. Could first-spike latency be a candidate neural code? Most studies measuring first-spike latency information assume that the brain has an independent reference for stimulus onset from which to extract latency. This assumption creates an obvious confound that casts doubt on the feasibility of first-spike latency codes. If latency is measured relative to an internal reference of stimulus onset calculated from the responses of the neural population, the information conveyed by the latency of single neurons might decrease because of correlated changes in latency across the population. Here we assess the effects of a realistic model of stimulus onset detection on the first-spike latency information conveyed by single neurons in the auditory system. Contrary to expectation, we find that on average, the information contained in single neurons does not decrease; in fact, the majority of neurons show a slight increase in the information conveyed by latency referenced to a population onset. Our results show that first-spike latency codes are a feasible mechanism for information transfer even when biologically plausible estimates of stimulus onset are taken into account.

Contribution of NMDA and AMPA Receptors to Temporal Patterning of Auditory Responses in the Inferior Colliculus

Although NMDA receptors (NMDARs) are associated with synaptic plasticity, they form an essential part of responses to sensory stimuli. We compared contributions of glutamatergic NMDARs and AMPA receptors (AMPARs) to auditory responses in the inferior colliculus (IC) of awake, adult mustached bats. We examined the magnitude and temporal pattern of responses to tonal signals in single units before, during, and after local micro-iontophoretic application of selective antagonists to AMPARs [NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide)] and NMDARs [CPP ((+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid)]. Combined blockade of AMPARs and NMDARs eliminated excitatory responses in nearly all neurons, whereas separate blockade of each receptor was quantitatively similar, causing substantial (> 50%) spike reductions in approximately 75% of units. The major result was that effects of receptor blockade were most closely related to the first-spike latency of a unit. Thus, AMPAR blockade substantially reduced spikes in all short-latency units (< 12 ms) but never in long-latency units (> or = 12 ms). NMDAR blockade had variable effects on short-latency units but reduced spikes substantially for all long-latency units. There were no distinct contributions of AMPARs and NMDARs to early and late elements of responses. Thus, AMPAR blockade reduced early (onset) spikes somewhat more effectively than NMDAR blockade in short-latency units, but NMDAR blockade reduced onset spikes more effectively in long-latency units. AMPAR and NMDAR blockade were equally effective in reducing later elements of sustained responses in short-latency units, whereas NMDAR blockade was much more effective in long-latency units. These results indicate that NMDARs play multiple roles for signal processing in adult IC neurons.

FM signals produce robust paradoxical latency shifts in the bat’s inferior colliculus

Previous studies in echolocating bats, Myotis lucifugus, showed that paradoxical latency shift (PLS) is essential for neural computation of target range and that a number of neurons in the inferior colliculus (IC) exhibit unit-specific PLS (characterized by longer first-spike latency at higher sound levels) in response to tone pulses at the unit's best frequency. The present study investigated whether or not frequency-modulated (FM) pulses that mimic the bat's echolocation sonar signals were equally effective in eliciting PLS. For two-thirds of PLS neurons in the IC, both FM and tone pulses could elicit PLS, but only FM pulses consistently produced unit-specific PLS. For the remainder of PLS neurons, only FM pulses effectively elicited PLS; these cells showed either no PLS or no response, to tone pulses. PLS neurons generally showed more pronounced PLS in response to narrow-band FM (each sweeping 20 kHz in 2 ms) pulse that contained the unit's best frequency. In addition, almost all PLS neurons showed duration-independent PLS to FM pulses, but the same units exhibited duration-dependent PLS to tone pulses. Taken together, when compared to tone pulses, FM stimuli can provide more reliable estimates of target range.

Reply to comment on “Auditory-nerve first-spike latency and auditory absolute threshold: A computer model”

Krisha [J. Acoust. Soc. Am., in press (2006)] has commented that an explanation based on presynaptic calcium accumulation at the inner hair cell is an incorrect explanation for the success of a model of the auditory periphery [Meddis, R., J. Acoustic. Soc. Am. 119, 406-417 (2006)] in explaining data on first-spike auditory nerve latency. This reply accepts the criticism and accepts the strength of an alternative explanation based on expected latencies in random sequences of low-probability events. This reply also goes on briefly to explore the application of this argument to other phenomena, including the dependence of absolute auditory threshold on the duration of the stimulus. This has wide-ranging implications for the concept of "temporal integration" in psychophysics.

Comment on “Auditory-nerve first-spike latency and auditory absolute threshold: A computer model” [J. Acoust. Soc. Am.119, 406–417 (2006)

A recent paper by Meddis [J. Acoust. Soc. Am. 119, 406-417 (2006)] shows that an existing model of the auditory nerve [Meddis and O'Mard, J. Acoust. Soc. Am. 117, 3787-3798 (2005)] is consistent with experimentally-measured first-spike latencies in the auditory nerve [Heil and Neubauer, J. Neurosci. 21, 7404-7415 (2001)]. The paper states that this consistency emerges because in the model, the calcium concentration inside the inner hair cell builds up over long periods of time (up to at least 200 ms) during tone presentation. It further states that integration over long time-scales happens despite the very short time constants (< 1 ms) used for the calcium dynamics. This letter demonstrates that these statements are incorrect. It is shown by simulation that calcium concentration inside the hair cell stage of the Meddis model rapidly reaches a steady state within a few milliseconds of a stimulus onset, exactly as expected from the short time-constant in the simple first-order differential equation used to model the calcium concentration. The success of the Meddis model in fitting experimental data actually confirms earlier results [Krishna, J. Comput. Neurosci. 13, 71-91 (2002a)] that show that the experimental data are a natural result of stochasticity in the synaptic events leading up to spike-generation in the auditory nerve; integration over long time scales is not necessary to model the experimental data.

Spike-Timing Codes Enhance the Representation of Multiple Simultaneous Sound-Localization Cues in the Inferior Colliculus

To preserve multiple streams of independent information that converge onto a neuron, the information must be re-represented more efficiently in the neural response. Here we analyze the increase in the representational capacity of spike timing over rate codes using sound localization cues as an example. The inferior colliculus receives convergent input from multiple auditory brainstem nuclei, including sound localization information such as interaural level differences (ILDs), interaural timing differences (ITDs), and spectral cues. Virtual space techniques were used to create stimulus sets varying in two sound-localization parameters each. Information about the cues was quantified using a spike distance metric that allows one to separate contributions to the information arising from spike rate and spike timing. Spike timing enhances the representation of spectral and ILD cues at timescales averaging 12 ms. ITD information, however, is carried by a rate code. Comparing responses to frozen and random noise shows that the temporal information is mainly attributable to phase locking to temporal stimulus features, with an additional first-spike latency component. With rate-based codes, there is significant confounding of information about two cues presented simultaneously, meaning that the cues cannot be decoded independently. Spike-timing-based codes reduce this confounded information. Furthermore, the relative representation of the cues often changes as a function of the time resolution of the code, implying that information about multiple cues can be multiplexed onto individual spike trains.

Role of hyperpolarization-activated conductances in the lateral superior olive: A modeling study

This modeling study examines the possible functional roles of two hyperpolarization-activated conductances in lateral superior olive (LSO) principal neurons. Inputs of these LSO neurons are transformed into an output, which provides a firing-rate code for a certain interaural sound intensity difference (IID) range. Recent experimental studies have found pharmacological evidence for the presence of both the Gh conductance as well as the inwardly rectifying outward GKIR conductance in the LSO. We addressed the question of how these conductances influence the dynamic range (IID versus firing rate). We used computer simulations of both a point-neuron model and a two-compartmental model to investigate this issue, and to determine the role of these conductances in setting the dynamic range of these neurons. The width of the dynamic regime, the frequency-current (f-I) function, first-spike latency, subthreshold oscillations and the interplay between the two hyperpolarization activated conductances are discussed in detail. The in vivo non-monotonic IID-firing rate function in a subpopulation of LSO neurons is in good correspondence with our simulation predictions. Two compartmental model simulation results suggest segregation of Gh and GKIR conductances on different compartments, as this spatial configuration could explain certain experimental results.

Responses of Neurons in the Rat's Ventral Nucleus of the Lateral Lemniscus to Monaural and Binaural Tone Bursts

Responses to monaural and binaural tone bursts were recorded from neurons in the rat's ventral nucleus of the lateral lemniscus (VNLL). Most of the neurons (55%) had V- or U-shaped frequency-tuning curves with a single clearly defined characteristic frequency (CF). However, many neurons had more complex, multipeaked tuning curves (37%), or other patterns (8%). Temporal firing patterns included both onset and sustained responses to contralateral tone bursts. Onset and sustained responses were distributed along the dorsoventral length of VNLL with no indication of segregation into different regions. Onset neurons had shorter average first-spike latencies than neurons with sustained responses (means, 8.3 vs. 14.8 ms). They also had less jitter, as reflected in the SD of first-spike latencies, than neurons with sustained responses (means, 0.59 and 4.2 ms, respectively). The extent of jitter decreased with an increase in stimulus intensity for neurons with sustained responses, but remained unchanged for onset neurons tested over the same range. Many neurons had binaural responses, primarily of the excitatory/inhibitory (EI) type, widely distributed along the dorsoventral extent of VNLL. Local application of the AMPA receptor antagonist NBQX reduced excitatory responses, indicating that responses were dependent on synaptic activity and not recorded from passing fibers. The results show that many neurons in VNLL have a precision of timing that is well suited for processing auditory temporal information. In the rat, these neurons are intermingled among cells with less precise temporal response features and include cells with binaural as well as monaural responses.

Auditory-nerve first-spike latency and auditory absolute threshold: A computer model

A computer model of the auditory periphery was used to address the question of what constitutes the physiological substrate of absolute auditory threshold. The model was first evaluated to show that it is consistent with experimental findings that auditory-nerve fiber spikes can be predicted to occur when the running integral of stimulus pressure reaches some critical value [P. Heil and H. Neubauer, J. Neurosci. 15, 7404-7415 (2001)]. It was then modified to examine two ways in which the accumulation and clearance of receptor presynaptic calcium might explain this effect. Both methods gave results that matched the animal data. It was also shown how the rate of clearance of presynaptic calcium could be used to explain the origin of differences between low and high spontaneous-rate fiber types. When spiking activity is aggregated across a number of similar high spontaneous-rate fibers and used as the input to a model of a cochlear nucleus coincidence neuron, its response can be used to judge whether or not a stimulus is present. A simulated psychophysical experiment then demonstrated that this simple decision procedure can reproduce measurements of absolute auditory threshold for tones in quiet where the threshold is a joint function of both time and level.