Spike train encoding by regular-spiking cells of the visual cortex

1. To study the encoding of input currents into output spike trains by regular-spiking cells, we recorded intracellularly from slices of the guinea pig visual cortex while injecting step, sinusoidal, and broadband noise currents. 2. When measured with sinusoidal currents, the frequency tuning of the spike responses was markedly band-pass. The preferred frequency was between 8 and 30 Hz, and grew with stimulus amplitude and mean intensity. 3. Stimulation with broadband noise currents dramatically enhanced the gain of the spike responses at low and high frequencies, yielding an essentially flat frequency tuning between 0.1 and 130 Hz. 4. The averaged spike responses to sinusoidal currents exhibited two nonlinearities: rectification and spike synchronization. By contrast, no nonlinearity was evident in the averaged responses to broadband noise stimuli. 5. These properties of the spike responses were not present in the membrane potential responses. The latter were roughly linear, and their frequency tuning was low-pass and well fit by a single-compartment passive model of the cell membrane composed of a resistance and a capacitance in parallel (RC circuit). 6. To account for the spike responses, we used a "sandwich model" consisting of a low-pass linear filter (the RC circuit), a rectification nonlinearity, and a high-pass linear filter. The model is described by six parameters and predicts analog firing rates rather than discrete spikes. It provided satisfactory fits to the firing rate responses to steps, sinusoids, and broadband noise currents. 7. The properties of spike encoding are consistent with temporal nonlinearities of the visual responses in V1, such as the dependence of response frequency tuning and latency on stimulus contrast and bandwidth. We speculate that one of the roles of the high-frequency membrane potential fluctuations observed in vivo could be to amplify and linearize the responses to lower, stimulus-related frequencies.     

Modeling inhibition of type II units in the dorsal cochlear nucleus

Type II units in the dorsal cochlear nucleus (DCN) are characterized by vigorous but nonmonotonic responses to best frequency tones as a function of sound pressure level, and relatively weak responses to noise. A model of DCN neural circuitry was used to explore two hypothetical mechanisms by which neurons may be endowed with type II unit response properties. Both mechanisms assume that type II units receive excitatory input from auditory nerve (AN) fibers and inhibitory input from an unspecified class of cochlear nucleus interneurons that also receive excitatory AN input. The first mechanism, a lateral inhibition (LI) model, supposes that type II units receive inhibitory input from a number of narrowly tuned interneurons whose best frequencies (BFs) flank the BF of the type II unit. Tonal stimuli near BF result in only weak inhibitory input, but broadband stimuli recruit enough lateral inhibitors to greatly weaken the type II unit response. The second mechanism, a wideband inhibition (WBI) model, supposes that type II units receive inhibitory input from interneurons that are broadly tuned so that they respond more vigorously to broadband stimuli than to tones. Physiological and anatomical evidence points to the possible existence of such a class of neurons in the cochlear nucleus. The model extends an earlier computer model of an iso-frequency DCN patch to multiple frequency slices and adds a population of interneurons to provide the inhibition to model type II units (called 12-cells). The results show that both mechanisms accurately simulate responses of type II units to tones and noise. An experimental paradigm for distinguishing the two mechanisms is proposed.     

Dissecting the frog inner ear with Gaussian noise. II. Temperature dependence of inner ear function

Wiener kernel analysis was used to characterize the auditory pathway from tympanic membrane to single primary auditory nerve fibers in the European edible frog, Rana esculenta. Nerve fiber signals were recorded in response to white Gaussian noise. By cross-correlating the noise stimulus and the nerve fiber response, we computed (1) the full second-order Wiener kernel, and (2) the diagonals of the zeroth- to fourth-order Wiener kernels. These diagonals are usually referred to as polynomial correlation functions. The measured Wiener kernels were fitted with a 'sandwich' model. A new fitting procedure was used to compute the response characteristics of (1) the first filter, (2) the static nonlinearity, and (3) the second filter, which form the functional components of the model. The first filter is a bandpass filter. In the majority of low frequency fibers, with best excitatory frequency (BEF) < 800 Hz, this filter was tuned to two frequencies. This dual tuning mechanism gives rise to 'off-diagonal' components in the second-order Wiener kernel. The static nonlinearity resembles a rectifier, and is dominated by second-order (quadratic) nonlinearity. As a function of BEF, the shape of the nonlinearity changes systematically. Finally, the last filter in the model was a low pass filter. Across fibers, its cutoff frequency f-3dB ranged from 106 to 434 Hz.     

Pathologic mechanoelectric transduction of outer hair cells as the cause of recruitment

It is believed that the sound-induced travelling wave in the mammalian cochlea is enhanced and sharpened by a positive feedback mechanism. This causes the passive linear basilar membrane growth function to become non-linear. The present paper shows that nonlinear basilar membrane vibration is due to the nonlinear growth function of the receptor potential of outer hair cells, which can be described by a 2nd-order Boltzmann function. Since intensity coding in the inner ear depends on an interaction of nonlinear basilar membrane motion and nerve fibers with three different types of synaptic threshold and growth function, the process is directly dependent on an intact mechanoelectrical transduction of outer hair cells. According to the proposed model, a loss in efficiency of outer hair cell mechanoelectrical transduction must lead to both a reduction in gain (i.e., hearing loss) and a linearizing of the response. As a result, once above threshold, the changes of stereociliary displacement, basilar membrane displacement and neural firing rate per unit change of sound intensity must be larger than for the healthy cochlea with its compressive nonlinearity.     

Effect of sodium benzoate on cerebral and hepatic energy metabolites in spf mice with congenital hyperammonemia

The outer hair cell (OHC) is known to have the ability to change its length in response to voltage changes across its membrane. The apparent function of this OHC motility is to enhance the tuning of the basilar membrane. The model presented in this paper represents the displacement-to-voltage and voltage-to-displacement transducers of the OHC explicitly, each as low-pass filter functions. The model results show that this OHC representation is sufficient to provide a model of cochlear mechanics with mechanical tuning at the inner hair cell which is comparable to the threshold tuning curves observed in single auditory nerve fibers. The enhancement of tuning provided by OHC motility can be interpreted as the combined action of a cochlear amplifier and a second filter. This model demonstrates that realistic cochlear tuning does not require intrinsic resonance in any cochlear structure other than the basilar membrane.     

Temporal patterns of the responses of auditory-nerve fibers to low-frequency tones

The temporal response patterns of auditory-nerve fibers to low-frequency tones were studied in anesthetized cats using period histograms. 'Peak-splitting' was observed mostly in fibers with lower characteristic frequencies (CF < 2 kHz) and with lower-frequency stimulation (< or = 500 Hz). The occurrence of peak-splitting, the number of peaks, and the time between the peaks were all dependent upon the stimulus frequency. The phases of responses, although complex functions of stimulus frequency, intensity, and the fiber's CF, clearly showed traveling-wave characteristics for all frequencies at or above 100 Hz. The amount of phase change with intensity was generally small for lower-frequency stimuli (< approximately 50 degrees), although larger phase changes (e.g., approximately 180 degrees) were occasionally seen with higher-frequency stimuli. At 50 and 100 Hz, the phase of neural responses in the basal region roughly corresponds to the maximum velocity of the basilar membrane towards scala tympani (as inferred from cochlear microphonic recordings).     

Basilar-membrane nonlinearity and the growth of forward masking

Forward masking growth functions were measured for pure-tone maskers and signals at 2 and 6 kHz as a function of the silent interval between the masker and signal. The inclusion of conditions involving short signals and short masker-signal intervals ensured that a wide range of signal thresholds were recorded. A consistent pattern was seen across all the results. When the signal level was below about 35 dB SPL the growth of masking was shallow, so that signal threshold increased at a much slower rate than masker level. When the signal level exceeded this value, the masking function steepened, approaching unity (linear growth) at the highest masker and signal levels. The results are inconsistent with an explanation for forward-masking growth in terms of saturating neural adaptation. Instead the data are well described by a model incorporating a simulation of the basilar-membrane response at characteristic frequency (which is almost linear at low levels and compressive at higher levels) followed by a sliding intensity integrator or temporal window. Taken together with previous results, the findings suggest that the principle nonlinearity in temporal masking may be the basilar membrane response function, and that subsequent to this the auditory system behaves as if it were linear in the intensity domain.     

Spatiotemporal tuning of low-frequency cells in the anteroventral cochlear nucleus

Low-frequency cells in the anteroventral cochlear nucleus (AVCN) can be sensitive to changes in the spatiotemporal pattern of discharges across their auditory nerve (AN) inputs (). This sensitivity suggests that these cells may be tuned to particular spatiotemporal patterns, or features, in the discharge patterns of populations of AN fibers. To evaluate and characterize this sensitivity, we developed a technique whereby the physiological responses of AVCN cells to wide-band noise were analyzed using the simulated response of a population of AN fibers to the same noise stimulus. By averaging the simulated two-dimensional spatiotemporal pattern of AN activity that preceded each AVCN discharge, it was possible to derive a two-dimensional reverse-correlation function that characterized the spatiotemporal tuning of each AVCN cell. The derived spatiotemporal tuning pattern represented a feature in the AN population response that was most likely to precede discharges of the AVCN cell. To test the spatiotemporal tuning characterizations, we used these patterns to predict the responses of cells to noise stimuli statistically independent from the stimuli used to characterize the cells. This technique provides a general tool for the study of any neural system that involves the analysis of spatiotemporal input patterns.     

Low-frequency suppression of auditory nerve responses to characteristic frequency tones

The effects of low-frequency (50, 100, 200 and 400 Hz) 'suppressor' tones on responses to moderate-level characteristic frequency (CF) tones were measured in chinchilla auditory nerve fibers. Two-tone interactions were evident at suppressor intensities of 70-100 dB SPL. In this range, the average response rate decreased as a function of increasing suppressor level and the instantaneous response rate was modulated periodically. At suppression threshold, the phase of suppression typically coincided with basilar membrane displacement toward scala tympani, regardless of CF. At higher suppressor levels, two suppression maxima coexisted, synchronous with peak basilar membrane displacement toward scala tympani and scala vestibuli. Modulation and rate-suppression thresholds did not vary as a function of spontaneous activity and were only minimally correlated with fiber sensitivity. Except for fibers with CF < 1 kHz, modulation and rate-suppression thresholds were lower than rate and phase-locking thresholds for the suppressor tones presented alone. In the case of high-CF fibers with low spontaneous activity, excitation thresholds could exceed suppression thresholds by more than 30 dB. The strength of modulation decreased systematically with increasing suppressor frequency. For a given suppressor frequency, modulation was strongest in high-CF fibers and weakest in low-CF fibers. The present findings strongly support the notion that low-frequency suppression in auditory nerve fibers largely reflects an underlying basilar membrane phenomenon closely related to compressive non-linearity.     

Psychoacoustic consequences of compression in the peripheral auditory system.

Input–output functions on the basilar membrane of the cochlea show a strong compressive nonlinearity at midrange levels for frequencies close to the characteristic frequency of a given place. This article shows how many different phenomena can be explained as consequences of this nonlinearity, including the "excess" masking produced when 2 nonsimultaneous maskers are combined, the nonlinear growth of forward masking with masker level, the influence of component phase on the effectiveness of complex forward maskers, changes in the ability to detect increments and decrements with level, temporal integration, and the influence of component phase and level on the perception of vowellike sounds. Cochlear hearing loss causes basilar-membrane responses to become more linear. This can account for loudness recruitment, linear additivity of nonsimultaneous masking, linear growth of forward masking, reduced temporal resolution for sounds with fluctuating envelopes, and reduced temporal integration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The intrinsic temporal properties of alpha and beta retinal ganglion cells are equivalent

BACKGROUND: Mammalian retinal ganglion cells have been traditionally classified on the basis of morphological and functional criteria, but as yet little is known about the intrinsic membrane properties of these neurons. This study has investigated these properties by making patch-clamp recordings from morphologically identified ganglion cells in the intact retina. RESULTS: The whole-cell configuration of the patch-clamp technique was used to assess the temporal tuning characteristics of alpha and beta cells, the two most extensively studied ganglion cell classes. Fourier analysis was used to examine discharge patterns in response to sinusoidal currents of different frequencies (1-50 Hz). With few exceptions, neurons responded in a stereotypic fashion to changes in temporal modulation, with their output initially increasing and then decreasing as a function of stimulus frequency. Moreover, peak responses in both cell classes were obtained at equivalent temporal frequencies. At high stimulus rates, response probability decreased, but the spikes remained phase-locked to the stimulus cycle, thereby enabling populations of cells to convey temporal information. A small number of ganglion cells did not show an appreciable decrease in output as a function of stimulus frequency, but these cells were not confined to either ganglion cell class. CONCLUSIONS: These findings provide the first evidence that the intrinsic temporal properties of alpha and beta cells are alike. Furthermore, the responses obtained to direct current injections were strikingly similar to those described previously with temporally modulated visual stimuli, suggesting that intrinsic membrane properties may shape the visual responses of alpha and beta cells to a larger degree than has been commonly assumed.     

Responses of anteroventral cochlear nucleus neurons of the unanesthetized decerebrate cat to click pairs as simulated echoes

To elucidate the contribution of the anteroventral cochlear nucleus (AVCN) to 'echo' processing, this study documents the responses of AVCN neurons to simulated echoes and compares them to those of auditory nerve (AN) fibers. Single unit discharges were recorded from 121 units in the AVCN of 21 unanesthetized decerebrate cats in response to click pairs with inter-click intervals ranging from 1 to 32 ms between 45 and 105 dB SPL re 20 microPa. Units were classified according to the post-stimulus time histogram (PSTH) and excitatory-inhibitory response area (EI-area) schemes. Based on their spontaneous rates (SR), units were subdivided into low- ( < 20 spikes/s) and high- ( > 20 spikes/s) SR groups. A majority of the units exhibited second-click responses whose recovery time courses were similar to those of AN fibers. These units included primary-like, chopper and onset units in the PSTH scheme and Types I, I/III and III units in the EI-area scheme. A minority of the units exhibited responses that were distinct from those of AN fibers, in that they had second-click response recovery times that were either markedly reduced or prolonged. This group of units included those with primary-like, chopper and onset PSTHs and Type I/III and III EI-areas. No significant difference was found in the second-click response among various PSTH or EI-area types. High-SR AVCN units exhibited a decrease in the second-click response with increasing level. In contrast, low-SR AVCN units showed little level-dependent change in the second-click responses. This SR-based difference was similar to that previously found among AN fibers. The present results suggest that, although a majority of AVCN units exhibit similar time courses of second-click response recovery to those of AN fibers, there do exist mechanisms in the cochlear nucleus that can substantially alter this representation. Furthermore, the difference between the second-click response recovery functions of low- and high-SR AVCN units and the consistency of this finding between AVCN and AN suggest that SR represents an important dimension for signal representation in the AVCN neurons.     

Computer simulation of shared input among projection neurons in the dorsal cochlear nucleus

Computer simulations of a network model of an isofrequency patch of the dorsal cochlear nucleus (DCN) were run to explore possible mechanisms for the level-dependent features observed in the cross-correlograms of pairs of type IV units in the cat and nominal type IV units in the gerbil DCN. The computer model is based on the conceptual model (of a cat) that suggests two sources of shared input to DCN's projection neurons (type IV units): excitatory input for auditory nerves and inhibitory input from interneurons (type II units). Use of tonal stimuli is thought to cause competition between these sources resulting in the decorrelation of type IV unit activities at low levels. In the model, P-cells (projection neurons), representing type IV units, receive inhibitory input from I-cells (interneurons), representing type II units. Both sets of model neurons receive a simulated excitatory auditory nerve (AN) input from same-CF AN fibers, where the AN input is modeled as a dead-time modified Poisson process whose intensity is given by a computationally tractable discharge rate versus sound pressure level function. Subthreshold behavior of each model neuron is governed by a set of normalized state equations. The computer mode has previously been shown to reproduce the major response properties of both type IV and type II units (e.g., rate-level curves and peri-stimulus time histograms) and the level-dependence of the functional type II-type IV inhibitory interaction. This model is adapted for the gerbil by simulating a reduced population of I-cells. Simulations were carried out for several auditory nerve input levels, and cross-correlograms were computed from the activities of pairs of P-cells for a complete (cat model) and reduced (gerbil model) population of I-cells. The resultant correlograms show central mounds (CMs), indicative of either shared excitatory or inhibitory input, for both spontaneous and tone-evoked driven activities. Similar to experimental results, CM amplitudes are a non-monotonic function of level and CM widths decrease as a function of level. These results are consistent with the hypothesis that shared excitatory input correlates the spontaneous activities of type IV units adn shared inhibitory input correlates their driven activities. The results also suggest that the decorrelation of the activities of type IV units can result from a reduced effectiveness of the AN input as a function of increasing level. Thus, competition between the excitatory and inhibitory inputs is not required.     

A model for binaural response properties of inferior colliculus neurons. I. A model with interaural time difference-sensitive excitatory and inhibitory inputs

The inferior colliculus (IC) model of Cai et al. [J. Acoust. Soc. Am. 103, 475-493 (1998)] simulated the binaural response properties of low-frequency IC neurons in response to various acoustic stimuli. This model, however, failed to simulate the sensitivities of IC neurons to dynamically changing temporal features, such as the sharpened dynamic interaural phase difference (IPD) functions. In this paper, the Cai et al. (1998) model is modified such that an adaptation mechanism, viz., an additional channel simulating a calcium-activated, voltage-independent potassium channel which is responsible for afterhyperpolarization, is incorporated in the IC membrane model. Simulations were repeated with this modified model, including the responses to pure tones, binaural beat stimuli, interaural phase-modulated stimuli, binaural clicks, and pairs of binaural clicks. The discharge patterns of the model in response to current injection were also studied and compared with physiological data. It was demonstrated that this model showed all the properties that were simulated by the Cai et al. (1998) model. In addition, it showed some properties that were not simulated by that model, such as the sharpened dynamic IPD functions and adapting discharge patterns in response to current injection.     

Linearity and normalization in simple cells of the macaque primary visual cortex

Simple cells in the primary visual cortex often appear to compute a weighted sum of the light intensity distribution of the visual stimuli that fall on their receptive fields. A linear model of these cells has the advantage of simplicity and captures a number of basic aspects of cell function. It, however, fails to account for important response nonlinearities, such as the decrease in response gain and latency observed at high contrasts and the effects of masking by stimuli that fail to elicit responses when presented alone. To account for these nonlinearities we have proposed a normalization model, which extends the linear model to include mutual shunting inhibition among a large number of cortical cells. Shunting inhibition is divisive, and its effect in the model is to normalize the linear responses by a measure of stimulus energy. To test this model we performed extracellular recordings of simple cells in the primary visual cortex of anesthetized macaques. We presented large stimulus sets consisting of (1) drifting gratings of various orientations and spatiotemporal frequencies; (2) plaids composed of two drifting gratings; and (3) gratings masked by full-screen spatiotemporal white noise. We derived expressions for the model predictions and fitted them to the physiological data. Our results support the normalization model, which accounts for both the linear and the nonlinear properties of the cells. An alternative model, in which the linear responses are subject to a compressive nonlinearity, did not perform nearly as well.     

Spectral envelope coding in cat primary auditory cortex: linear and non-linear effects of stimulus characteristics

Electrophysiological studies in mammal primary auditory cortex have demonstrated neuronal tuning and cortical spatial organization based upon spectral and temporal qualities of the stimulus including: its frequency, intensity, amplitude modulation and frequency modulation. Although communication and other behaviourally relevant sounds are usually complex, most response characterizations have used tonal stimuli. To better understand the mechanisms necessary to process complex sounds, we investigated neuronal responses to a specific class of broadband stimuli, auditory gratings or ripple stimuli, and compared the responses with single tone responses. Ripple stimuli consisted of 150-200 frequency components with the intensity of each component adjusted such that the envelope of the frequency spectrum is sinusoidal. It has been demonstrated that neurons are tuned to specific characteristics of those ripple stimulus including the intensity, the spacing of the peaks, and the location of the peaks and valleys (C. E. Schreiner and B. M. Calhoun, Auditory Neurosci., 1994; 1: 39-61). Although previous results showed that neuronal response strength varied with the intensity and the fundamental frequency of the stimulus, it is shown here that the relative response to different ripple spacings remains essentially constant with changes in the intensity and the fundamental frequency. These findings support a close relationship between pure-tone receptive fields and ripple transfer functions. However, variations of other stimulus characteristics, such as spectral modulation depth, result in non-linear alterations in the ripple transformation. The processing between the basilar membrane and the primary auditory cortex of broadband stimuli appears generally to be non-linear, although specific stimulus qualities, including the phase of the spectral envelope, are processed in a nearly linear manner.     

The level dependence of response phase: observations from cochlear hair cells

Hair cell responses are recorded from third turn of the guinea pig cochlea in order to define the relationship between hair cell depolarization and position of the basilar membrane. Because the latter is determined locally, using the cochlear microphonic recorded in the organ of Corti (OC) fluid space, no corrections are required to compensate traveling wave and/or synaptic delays. At low levels, inner hair cells (IHC) depolarize near basilar membrane velocity to scala vestibuli reflecting the free standing nature of their stereocilia. At high levels, the time of depolarization changes rapidly from velocity to scala vestibuli to the scala tympani phase of the basilar membrane response. This change in response phase, recorded in the fundamental component of the IHC response, is associated with a decrease in response magnitude. The absence of this behavior in OC and outer hair cell responses implies that basilar membrane mechanics may not be responsible for these response patterns. Because these features are reminiscent of the magnitude notches and the large phase shifts observed in single unit responses at high stimulus levels, they provide the IHC correlates of these phenomena.     

The stretching nonlinearity of the basilar membrane in a cochlear model

Recently it has been suggested that the stretching nonlinearity of the basilar membrane might be responsible for the observed nonlinear behaviour of basilar membrane motion. In the present study this type of nonlinearity is investigated, both by estimating its influence in an analytical manner, and by calculating its effect numerically, using a regular pertubation method. The conclusion reads that the stretching nonlinearity does not explain the observed nonlinear phenomena; not only is stretching negligible at normal sound levels, but it also fails to fit the data qualitatively, because of its typical hard-spring effect. In consequence, the origin of cochlear nonlinearity is not to be sought in the macromechanics of the inner ear, but in the more detailed processes in th organ of Corti-tectorial membrane complex.     

Contrast gain control and fine spatial discriminations

The effect of contrast gain control mechanisms on discrimination between highly similar simple and complex stimuli is examined, with a focus on how discrimination accuracy changes as a function of the contrast of stimulus components. Two models of contrast gain control are evaluated. In both, the response of each pathway is attenuated by a factor determined by the total activity in a large pool of pathways. One model bases attenuation on the sum of linear filter responses within this pool; the other, based on Heeger's contrast energy-driven model [J. Neurophysiol. 70, 1985 (1993)], uses squared filter response. Predictions generated from the models are compared with data from experiments reported here and from the literature. Predictions are made for simple grafting stimuli of different sizes and for stimuli to which a second grafting component is added either as a second cue or as a mask. With one exception, predictions of the models agree closely with each other and with the data. The exception is a masking study that differentiates the models and supports the filter-driven model over the energy-driven model.