Single-neuron modeling of LSO unit responses.

We investigated, using a computational model, the biophysical correlates of measured discharge patterns of lateral superior olive (LSO) neuron responses to monaural and binaural stimuli. The model's geometry was based on morphological data, and static electric properties of the model agree with available intracellular responses to hyperpolarizing current pulses. Inhibitory synapses were located on the soma and excitatory ones on the dendrites, which were modeled as passive cables. The active properties of the model were adjusted to agree with statistical measures derived from extracellular recordings. Calcium-dependent potassium channels supplemented the usual Hodgkin-Huxley characterization for the soma to produce observed serial interspike interval dependence characteristics. Intracellular calcium concentration is controlled by voltage- and calcium-dependent potassium channels and by calcium diffusion and homeostatic mechanisms. By adjusting the density of the calcium-dependent potassium channels, we could span the observed range of transient response patterns found in different LSO neurons. Inputs from the two ears were modeled as Poisson processes to describe the responses to tone-burst stimuli. Transient and sustained responses to monaural and binaural tone-burst stimuli over a wide range of stimulus conditions could be well described by varying only the model's inputs. As found in recordings, model responses having similar discharge rates but different binaural stimulus combinations exhibited differences in interval statistics.

Input from the medial nucleus of trapezoid body to an interaural level detector.

The medial nucleus of the trapezoid body (MNTB) contains components of a neural network that functions as an interaural level difference (ILD) detector. In the cat, lateral superior olivary (LSO) neurons compare the contralateral inhibitory input from the MNTB with an excitatory input form the ipsilateral anteroventral cochlear nucleus to extract information about binaural stimuli. To better specify the inhibitory inputs to the LSO and gain a better understanding of the inhibitory component of the LSO network, the response characteristics of MNTB neurons were examined in cats under stimulus conditions similar to those used to study LSO inhibitory responses. The inhibitory tuning curves of LSO units were wider than the tuning curves of MNTB units. Hence, MNTB neurons with similar, but not identical, characteristic frequencies converge to provide inhibitory input to single LSO neurons. Variations in the number of converging MNTB inputs produced a range of LSO excitatory-inhibitory threshold differences, thus creating a coding mechanism for representing the ILD. Convergence of MNTB inputs also increased the dynamic range over which contralateral stimulus level effects LSO binaural responses beyond the dynamic ranges of individual MNTB units, thus expanding the ILD range encoded by the LSO network. The differences between the first-spike latencies of MNTB and LSO tone burst responses were small and the precision of the LSO first-spike discharges was significantly greater than that of MNTB units. As tone bursts delivered simultaneously to the two ears can consistently inhibit LSO first-spike discharges, the inhibitory input must match the LSO precision by converging a number of the more variably timed MNTB discharges. Because of their precision LSO first-spike discharges may be used to encode interaural time-of-arrival differences of mid- to high-frequency transients. These findings add to the foundation for a comprehensive network model that describes the inputs to the LSO as point processes, delimits the biophysical mechanisms underlying excitatory and inhibitory interactions at the single neuron level, and reveals how these inputs determine the response to different binaural stimulus conditions.

Transient effects during the chopping response of LSO neurons.

The initial transient chopping response of LSO neuron discharges to both monaural and binaural tone-burst stimuli in the context of a previously developed point process model of the later sustained response is analyzed and modeled. The analysis reveals the nature of the initial transient response to stimulus onset: The model's stimulus-dependent parameters vary with poststimulus-onset time while the neuron's intrinsic recovery characteristics remain constant throughout the response. By applying maximum-likelihood estimation techniques to determine the time course of the stimulus-dependent parameters, it was found that the initial excitatory and inhibitory effects decay exponentially, with their ratio determining the instantaneous rate of firing and their relative latency determining the extent of the initial chopping pattern. The "absolute" and apparent deadtime also vary exponentially during the transient portion of the response. It is concluded that the recovery characteristics of LSO neurons and, the exponential nature of the transient effects give rise to a tightly distributed latency period and a regular chopping response pattern that could encode azimuthal information.

A nonstationary Poisson point process describes the sequence of action potentials over long time scales in lateral-superior-olive auditory neurons.

The behavior of lateral-superior-olive (LSO) auditory neurons over large time scales was investigated. Of particular interest was the determination as to whether LSO neurons exhibit the same type of fractal behavior as that observed in primary VIII-nerve auditory neurons. It has been suggested that this fractal behavior, apparent on long time scales, may play a role in optimally coding natural sounds. We found that a nonfractal model, the nonstationary dead-time-modified Poisson point process (DTMP), describes the LSO firing patterns well for time scales greater than a few tens of milliseconds, a region where the specific details of refractoriness are unimportant. The rate is given by the sum of two decaying exponential functions. The process is completely specified by the initial values and time constants of the two exponentials and by the dead-time relation. Specific measures of the firing patterns investigated were the interspike-interval (ISI) histogram, the Fano-factor time curve (FFC), and the serial count correlation coefficient (SCC) with the number of action potentials in successive counting times serving as the random variable. For all the data sets we examined, the latter portion of the recording was well approximated by a single exponential rate function since the initial exponential portion rapidly decreases to a negligible value. Analytical expressions available for the statistics of a DTMP with a single exponential rate function can therefore be used for this portion of the data. Good agreement was obtained among the analytical results, the computer simulation, and the experimental data on time scales where the details of refractoriness are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

The brain stem evoked response and medial nucleus of the trapezoid body.

Single-unit responses of cat superior olivary complex neurons to acoustic stimuli were examined to determine whether the units' action potentials were sufficiently synchronized to contribute to the brain stem evoked response. The medial nucleus of the trapezoid body and lateral superior olive are two major nuclei within the cat superior olivary complex. The first-spike discharge latencies of medial nucleus of the trapezoid body and lateral superior olivary neurons to monaural presentations of tone burst stimuli were measured as a function of stimulus level. Evidence is provided to support the hypotheses that in cat the medial nucleus of the trapezoid body may contribute directly to the monaural brain stem evoked response by producing action potentials synchronized to stimulus onset and may also contribute indirectly to the brain stem evoked response binaural difference wave bc by inhibiting the lateral superior olive unit excitatory responses synchronized to stimulus onset.

Excitation effects on LSO unit sustained responses: point process characterization.

LSO units recover from a spike discharge in a characteristic way, modeled by an intrinsic recovery function that is stimulus invariant up to a scaling factor and a shifting constant. Data analysis shows that the effect of increasing excitatory stimulus level can be described by amplifying the intrinsic recovery function and by shifting it toward shorter intervals. The shifting process secondarily interacts with the absolute deadtime to produce the response characteristics of the three LSO unit types. Decreased excitation is clearly distinguished from inhibition, which affects the scaling, but not the time origin, of the recovery. We conclude that both excitatory and inhibitory stimulus levels are encoded in the timing of LSO unit discharges.

Excitatory/inhibitory interaction in the LSO revealed by point process modeling.

We studied lateral superior olivary (LSO) unit responses to binaural tone-bursts using a general point process approach. We show that inhibition of the ipsilaterally elicited response by contralateral stimulation cannot be modeled simply as a reduction of the ipsilateral input. Statistical analyses reveal that inhibition operates by scaling the intensity of the point process describing the ipsilateral response. In some cases the scaling process has secondary effects: Binaurally elicited discharges produce bimodal interspike interval histograms from units that produce unimodal interval histograms under monaural stimulation. We present a specific point process model that describes the scaling process and successfully replicates the observed responses to monaural and binaural stimulation of the three types of LSO units: slow choppers, fast choppers, and bimodal units. We interpret scaling as a shunting inhibitory process in these LSO neurons. By relating scaling magnitude to interaural level difference, we demonstrate the spatial sensitivity of LSO units.

Function-based modeling of binaural processing: interaural level.

The function-based modeling approach applies optimal estimation theory to sensory phenomena for determining how relevant sensory parameters are extracted from stimuli and how the characteristics of the resulting optimal processing system compare with those of the sensory system. This approach is applied to the neural system involved in the binaural localization of sustained high-frequency sound sources: the lateral superior olive (LSO) of the cat. The sufficient statistic produced by the optimal processor is shown to be related to the interaural level difference. This level difference is processed optimally when the inputs are excitatory from one ear and inhibitory from the opposite ear. Response characteristics of LSO single units are remarkably similar, thereby strongly supporting the notion that LSO units are intimately involved in high-frequency binaural hearing. Optimal processor theory is also used to assess lateralization performance when the hearing thresholds of the two ears differ.

The inhibition of cat lateral superior olive unit excitatory responses to binaural tone bursts. I. The transient chopper response.

1. The temporal properties of lateral superior olivary (LSO) unit discharges to binaural tone bursts were studied to determine the general time course and statistical properties of these discharges and to provide a basis for extending a point process model of LSO unit monaural discharges to describe their binaural discharges. Single-unit activity was recorded extracellularly from the LSO of the anesthetized cat. The initial transient and the gross temporal features of LSO unit discharges to binaural simultaneous tone bursts are examined in this paper. 2. The poststimulus time (PST) histograms generated by LSO unit discharges to monaural and binaural tone bursts illustrated that the ipsilaterally elicited tone-burst discharges were most strongly inhibited during the initial segment of the binaural response and that the degree of inhibition decreased (i.e., discharge rate increased) as the poststimulus onset time increased. Hence, the contralateral inhibitory effect "adapts" in a manner similar to the ipsilaterally elicited discharges. 3. When the interaural level difference was decreased, the degree of discharge inhibition increased: the period of maximal inhibition spread to shorter and longer poststimulus onset times as the contralateral latency decreased and as the contralateral response magnitude increased. The latency of the inhibitory effect could decrease sufficiently to result in the suppression of the first spike of the ipsilateral discharge. Also, when the binaural stimulus was of sufficient intensity, an increase in spike output, the OFF discharge, was often observed during the last 1-10 ms of the response. 4. It was concluded that the initial and general time course of the binaural response could serve as cues of binaural stimulus level, interaural level differences, and interaural time-of-arrival differences of high-frequency stimuli. The binaural response could be discriminated from a monaural response of similar discharge rate as the former either occurred with shorter latency or, when the first spike was suppressed, with much longer and/or more variable latency than the latter. The gross temporal differences between the monaural and binaural responses could be accounted for in terms of differences in certain gross temporal features (e.g., latency and adaptation) of the ipsilateral and contralateral responses. 5. The effect of stimulating the contralateral ear was not limited to the inhibition of discharges. The timing of a discharge to an ipsilateral stimulus could be perturbed (lengthened) by a contralateral stimulus at levels below that which suppressed the discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

The inhibition of cat lateral superior olive unit excitatory responses to binaural tone bursts. II. The sustained discharges.

1. Preliminary to extending a point process model of lateral superior olive (LSO) unit activity to describe the units' binaural responses, the statistical properties of their discharges to binaural tone bursts were studied. The hypothesis that stimulation of the contralateral ear results in the simple reduction of the ipsilateral input was also examined. Single-unit activity was recorded extracellularly from the LSO of the anesthetized cat. The sustained discharges to characteristic frequency (CF) tone bursts presented simultaneously to the two ears were examined to determine whether the fine temporal (statistical) properties of these discharges differed from those of the discharges elicited by stimulating the ipsilateral ear alone. 2. The major effect of simultaneously stimulating the contralateral ear was the inhibition (i.e., the reduction in the mean discharge rate) of the sustained discharges to the ipsilateral control stimulus. The temporal pattern of discharges to the ipsilateral stimulus was also affected by stimulation of the contralateral ear. The discharges to binaural stimulation were more irregular in pattern: they often produced bimodal or multimodal interval histograms where unimodal interval histograms had been produced by the discharges to the ipsilateral control stimulus alone. The hazard function, an estimate of the unit recovery function, also often differed in form for the binaural and monaural discharges. 3. The binaural discharges could be distinguished from an ipsilaterally elicited discharge of comparable mean rate: there was a greater incidence of "short" interspike intervals in the binaural discharge. These short interspike intervals occurred most frequently in the discharges to the ipsilateral control stimulus alone and infrequently in the discharges to an ipsilateral stimulus that produced a mean rate similar to that of the binaural discharge. Thus the dead time estimates derived from the binaural discharges were more similar to the estimates derived from the ipsilateral control discharges than to those derived from the comparable-rate ipsilaterally elicited discharges. 4. Although the measures of the recovery properties of LSO unit discharges differed under monaural and binaural stimulus conditions, the serial dependence observed between successive interspike intervals in the binaurally elicited discharges was similar to that in the ipsilaterally elicited discharges. The conditional mean function, an estimate of the serial dependence or unit shifting function, did not differ greatly in form for the monaural and binaural discharges.(ABSTRACT TRUNCATED AT 400 WORDS)

Application of a point process model to responses of cat lateral superior olive units to ipsilateral tones.

A general point process theory is developed to describe discharges recorded from lateral superior olivary units of the cat responding to ipsilaterally presented tone bursts and continuous tones. Statistical analysis of the stationary portion of the sequence of interspike intervals demonstrated that, for most units, the duration of each interval is statistically dependent only on the duration of the previous interval. A specific point process model is derived based on this analysis to describe the measured serial dependence as well as the deadtimes observed in interval histograms. The statistical dependence is well described as a shift of the interspike interval distribution, the shift depending on the duration of the previous interval. This model is then used to simulate the initial chopping in the tone burst responses. It is concluded that chopping responses and serial dependence do not result from properties of the unit's inputs; rather, they are consequences of the inherent characteristics of the unit.

The effects of ipsilateral tone burst stimulus level on the discharge patterns of cat lateral superior olivary units.

Discharges were recorded extracellularly from single units localized in the lateral superior olive (LSO) of barbiturate anesthetized cats. The statistical properties of the unit discharges to monaurally presented tone bursts were determined. Increasing the stimulus level of an ipsilaterally presented tone burst produced an increase in the discharge rate and the emergence and growth of a time-locked discharge pattern in the initial portion of the response. The initial time-locked response was transient and was followed by a nontime-locked sustained response. In the sustained portion, increasing stimulus level produced increases in rate and changes in the interspike interval statistics. Average rate and interval statistics were found to be systematically related. LSO units were differentiated on the basis of rate and pattern of their initial discharges into two main types: the fast and slow chopping units. An analysis of the results indicated that some aspects of response type differences may be related to input characteristics rather than to neuron response mechanisms.

Functional organization of lateral cell groups of cat superior olivary complex.

1. Single-unit discharges to auditory stimuli were recorded extracellularly from superior olivary complex (SOC) units located lateral to the medial superior olive. Stimuli consisted of monaurally or binaurally presented tone bursts. The response measures obtained were effective ear, nature of effect, stimulus-frequency representation, maximum output, latency of response, and temporal pattern of tone burst-elicited discharges. Electrolytic marks were made at the unit studied or at the end of the electrode tract and in the medial superior olive. Following each experiment the locations of the units studied were determined histologically. An atlas of the laterally located SOC cell groups was developed to permit classification of units on the basis of localization within cell groups. Units were also classified according to the effects of stimulating the two ears. 2. All SOC units located lateral to the medial superior olive were excited by stimulation of the ipsilateral ear. Stimulation of the contralateral ear either excited, inhibited, had no effect, or had a potentiating effect on the discharges elicited by stimulating the ipsilateral ear. 3. Most lateral superior olivary (LSO) units were inhibited by contralateral stimulation, were narrowly tuned, produced low to high levels of maximum output, had short latencies, and produced regular discharge patterns characterized by chopper PST histograms with narrow initial peaks. 4. Most units within the caudal margins of the LSO (pLSO) were not affected or were inhibited by a contralateral stimulus; many were broadly tuned and exhibited intensity functions with large dynamic range and low slope. These units also had long latencies and produced chopper PST histograms with wide initial peaks. 5. Most units located dorsal to the LSO (DPO and DLPO) were not affected by the contralateral stimulus, were narrowly tuned, produced moderate levels of maximum discharge, had long latencies, and produced chopper PST histograms with wide initial peaks. 6. Units located ventral to the LSO appeared to have response characteristics related to unit location. Most units below the ventral hilum of the LSO (VLPO) were inhibited by the contralateral stimulus and many were broadly tuned VLPO units produced wide or poorly defined narrow-chopper discharge patterns and intensity functions with high maximum output. Most units located ventral to the lateral loop of the LSO (LNTB) were not affected by the contralateral stimulus and had response characteristics that may be related to the rostrocaudal location of the unit. 7. The cell groups located dorsal and ventral to the LSO were tonotopically organized with low-frequency-sensitive units located laterally and high-frequency-sensitive units located medially. The units located along the caudal margins of the LSO had a tonotopic organization similar to that of the LSO.