Experience-Dependent Plasticity in Nucleus Laminaris of the Barn Owl.

Interaural time differences (ITDs) are a major cue for sound localization and change with increasing head size. Since the barn owl's head width more than doubles in the month after hatching, we hypothesized that the development of their ITD detection circuit might be modified by experience. To test this, we raised owls with unilateral ear inserts that delayed and attenuated the acoustic signal, and then measured the ITD representation in the brainstem nucleus laminaris (NL) when they were adults. The ITD circuit is composed of delay line inputs to coincidence detectors, and we predicted that plastic changes would lead to shorter delays in the axons from the manipulated ear, and complementary shifts in ITD representation on the two sides. In owls that received ear inserts starting around P14, the maps of ITD shifted in the predicted direction, but only on the ipsilateral side, and only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. The contralateral map did not change. Thus, experience-dependent plasticity of the ITD circuit occurs in NL, and our data suggest that ipsilateral and contralateral delays are independently regulated. As a result, altered auditory input during development leads to long-lasting changes in the representation of ITD.Significance Statement The early life of barn owls is marked by increasing sensitivity to sound, and by increasing ITDs. Their prolonged post-hatch development allowed us to examine the role of altered auditory experience in the development of ITD detection circuits. We raised owls with a unilateral ear insert and found that their maps of ITD were altered by experience, but only in those tonotopic regions ipsilateral to the occluded ear that had not experienced auditory stimulation prior to insertion. This experience-induced plasticity allows the sound localization circuits to be customized to individual characteristics, such as the size of the head, and potentially to compensate for imbalanced hearing sensitivities between the left and right ears.

Cochlear aging disrupts the correlation between spontaneous rate- and sound-level coding in auditory nerve fibers.

The spiking activity of auditory nerve fibers (ANFs) transmits information about the acoustic environment from the cochlea to the central auditory system. Increasing age leads to degeneration of cochlear tissues, including the sensory hair cells and stria vascularis. Here, we aim to identify the functional effects of such age-related cochlear pathologies of ANFs. Rate-level functions (RLFs) were recorded from single-unit ANFs of young adult (n = 52, 3-12 months) and quiet-aged (n = 24, >36 months) Mongolian gerbils of either sex. RLFs were used to determine sensitivity and spontaneous rates (SRs) and were classified into flat-saturating, sloping-saturating, and straight categories, as previously established. A physiologically based cochlear model, adapted for the gerbil, was used to simulate the effects of cochlear degeneration on ANF physiology. In ANFs tuned to low frequencies (<3.5 kHz), SR was lower in those of aged gerbils, while an age-related loss of low-SR fibers was evident in ANFs tuned to high frequencies. These changes in SR distribution did not affect the typical SR versus sensitivity correlation. The distribution of RLF types among low-SR fibers, however, shifted toward that of high-SR fibers, specifically showing more fast-saturating and fewer sloping-saturating RLFs. A modeled striatal degeneration, which affects the combined inner hair cell and synaptic output, reduced SR but left RLF type unchanged. An additional reduced basilar membrane gain, which decreased sensitivity, explained the changed RLF types. Overall, the data indicated age-related changes in the characteristics of single ANFs that blurred the established relationships between SR and RLF types.NEW & NOTEWORTHY Auditory nerve fibers, which connect the cochlea to the central auditory system, change their encoding of sound level in aged gerbils. In addition to a general shift to higher levels, indicative of decreased sensitivity, level coding was also differentially affected in fibers with low- and high-spontaneous rates. Loss of low-spontaneous rate fibers, combined with a general decrease of spontaneous rate, further blurs the categorization of auditory nerve fiber types in the aged gerbil.

Robustness of neuronal tuning to binaural sound localization cues against age-related loss of inhibitory synaptic inputs.

Sound localization relies on minute differences in the timing and intensity of sound arriving at both ears. Neurons of the lateral superior olive (LSO) in the brainstem process these interaural disparities by precisely detecting excitatory and inhibitory synaptic inputs. Aging generally induces selective loss of inhibitory synaptic transmission along the entire auditory pathways, including the reduction of inhibitory afferents to LSO. Electrophysiological recordings in animals, however, reported only minor functional changes in aged LSO. The perplexing discrepancy between anatomical and physiological observations suggests a role for activity-dependent plasticity that would help neurons retain their binaural tuning function despite loss of inhibitory inputs. To explore this hypothesis, we use a computational model of LSO to investigate mechanisms underlying the observed functional robustness against age-related loss of inhibitory inputs. The LSO model is an integrate-and-fire type enhanced with a small amount of low-voltage activated potassium conductance and driven with (in)homogeneous Poissonian inputs. Without synaptic input loss, model spike rates varied smoothly with interaural time and level differences, replicating empirical tuning properties of LSO. By reducing the number of inhibitory afferents to mimic age-related loss of inhibition, overall spike rates increased, which negatively impacted binaural tuning performance, measured as modulation depth and neuronal discriminability. To simulate a recovery process compensating for the loss of inhibitory fibers, the strength of remaining inhibitory inputs was increased. By this modification, effects of inhibition loss on binaural tuning were considerably weakened, leading to an improvement of functional performance. These neuron-level observations were further confirmed by population modeling, in which binaural tuning properties of multiple LSO neurons were varied according to empirical measurements. These results demonstrate the plausibility that homeostatic plasticity could effectively counteract known age-dependent loss of inhibitory fibers in LSO and suggest that behavioral degradation of sound localization might originate from changes occurring more centrally.

Temporal Coding of Single Auditory Nerve Fibers Is Not Degraded in Aging Gerbils.

People suffering from age-related hearing loss typically present with deficits in temporal processing tasks. Temporal processing deficits have also been shown in single-unit studies at the level of the auditory brainstem, midbrain, and cortex of aged animals. In this study, we explored whether temporal coding is already affected at the level of the input to the central auditory system. Single-unit auditory nerve fiber recordings were obtained from 41 Mongolian gerbils of either sex, divided between young, middle-aged, and old gerbils. Temporal coding quality was evaluated as vector strength in response to tones at best frequency, and by constructing shuffled and cross-stimulus autocorrelograms, and reverse correlations, from responses to 1 s noise bursts at 10-30 dB sensation level (dB above threshold). At comparable sensation levels, all measures showed that temporal coding was not altered in auditory nerve fibers of aging gerbils. Furthermore, both temporal fine structure and envelope coding remained unaffected. However, spontaneous rates were decreased in aging gerbils. Importantly, despite elevated pure tone thresholds, the frequency tuning of auditory nerve fibers was not affected. These results suggest that age-related temporal coding deficits arise more centrally, possibly due to a loss of auditory nerve fibers (or their peripheral synapses) but not due to qualitative changes in the responses of remaining auditory nerve fibers. The reduced spontaneous rate and elevated thresholds, but normal frequency tuning, of aged auditory nerve fibers can be explained by the well known reduction of endocochlear potential due to strial dysfunction in aged gerbils.SIGNIFICANCE STATEMENT As our society ages, age-related hearing deficits become ever more prevalent. Apart from decreased hearing sensitivity, elderly people often suffer from a reduced ability to communicate in daily settings, which is thought to be caused by known age-related deficits in auditory temporal processing. The current study demonstrated, using several different stimuli and analysis techniques, that these putative temporal processing deficits are not apparent in responses of single-unit auditory nerve fibers of quiet-aged gerbils. This suggests that age-related temporal processing deficits may develop more central to the auditory nerve, possibly due to a reduced population of active auditory nerve fibers, which will be of importance for the development of treatments for age-related hearing disorders.

Binaural responses in the auditory midbrain of chicken (Gallus gallus).

The auditory midbrain is the location in which neurons represent binaural acoustic information necessary for sound localization. The external nucleus of the midbrain inferior colliculus (IC) of the barn owl is a classic example of an auditory space map, but it is unknown to what extent the principles underlying its formation generalize to other, less specialized animals. We characterized the spiking responses of 139 auditory neurons in the IC of the chicken (Gallus gallus) in vivo, focusing on their sensitivities to the binaural localization cues of interaural time (ITD) and level (ILD) differences. Most units were frequency-selective, with best frequencies distributed unevenly into low-frequency and high-frequency (> 2 kHz) clusters. Many units showed sensitivity to either ITD (65%) or ILD (66%) and nearly half to both (47%). ITD selectivity was disproportionately more common among low-frequency units, while ILD-only selective units were predominantly tuned to high frequencies. ILD sensitivities were diverse, and we thus developed a decision tree defining five types. One rare type with a bell-like ILD tuning was also selective for ITD but typically not frequency-selective, and thus matched the characteristics of neurons in the auditory space map of the barn owl. Our results suggest that generalist birds such as the chicken show a prominent representation of ITD and ILD cues in the IC, providing complementary information for sound localization, according to the duplex theory. A broadband response type narrowly selective for both ITD and ILD may form the basis for a representation of auditory space.

Neuronal population model of globular bushy cells covering unit-to-unit variability.

Computations of acoustic information along the central auditory pathways start in the cochlear nucleus. Bushy cells in the anteroventral cochlear nucleus, which innervate monaural and binaural stations in the superior olivary complex, process and transfer temporal cues relevant for sound localization. These cells are categorized into two groups: spherical and globular bushy cells (SBCs/GBCs). Spontaneous rates of GBCs innervated by multiple auditory nerve (AN) fibers are generally lower than those of SBCs that receive a small number of large AN synapses. In response to low-frequency tonal stimulation, both types of bushy cells show improved phase-locking and entrainment compared to AN fibers. When driven by high-frequency tones, GBCs show primary-like-with-notch or onset-L peristimulus time histograms and relatively irregular spiking. However, previous in vivo physiological studies of bushy cells also found considerable unit-to-unit variability in these response patterns. Here we present a population of models that can simulate the observed variation in GBCs. We used a simple coincidence detection model with an adaptive threshold and systematically varied its six parameters. Out of 567000 parameter combinations tested, 7520 primary-like-with-notch models and 4094 onset-L models were selected that satisfied a set of physiological criteria for a GBC unit. Analyses of the model parameters and output measures revealed that the parameters of the accepted model population are weakly correlated with each other to retain major GBC properties, and that the output spiking patterns of the model are affected by a combination of multiple parameters. Simulations of frequency-dependent temporal properties of the model GBCs showed a reasonable fit to empirical data, supporting the validity of our population modeling. The computational simplicity and efficiency of the model structure makes our approach suitable for future large-scale simulations of binaural information processing that may involve thousands of GBC units.

Neural rate difference model can account for lateralization of high-frequency stimuli.

Lateralization of complex high-frequency sounds is conveyed by interaural level differences (ILDs) and interaural time differences (ITDs) in the envelope. In this work, the authors constructed an auditory model and simulate data from three previous behavioral studies obtained with, in total, over 1000 different amplitude-modulated stimuli. The authors combine a well-established auditory periphery model with a functional count-comparison model for binaural excitatory-inhibitory (EI) interaction. After parameter optimization of the EI-model stage, the hemispheric rate-difference between pairs of EI-model neurons relates linearly with the extent of laterality in human listeners. If a certain ILD and a certain envelope ITD each cause a similar extent of laterality, they also produce a similar rate difference in the same model neurons. After parameter optimization, the model accounts for 95.7% of the variance in the largest dataset, in which amplitude modulation depth, rate of modulation, modulation exponent, ILD, and envelope ITD were varied. The model also accounts for 83% of the variances in each of the other two datasets using the same EI model parameters.

Contribution of action potentials to the extracellular field potential in the nucleus laminaris of barn owl.

Extracellular field potentials (EFP) are widely used to evaluate in vivo neural activity, but identification of multiple sources and their relative contributions is often ambiguous, making the interpretation of the EFP difficult. We have therefore analyzed a model EFP from a simple brainstem circuit with separable pre- and postsynaptic components to determine whether we could isolate its sources. Our previous papers had shown that the barn owl neurophonic largely originates with spikes from input axons and synapses that terminate on the neurons in the nucleus laminaris (NL) (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274-2290, 2010; Kuokkanen PT, Ashida G, Carr CE, Wagner H, Kempter R. J Neurophysiol 110: 117-130, 2013; McColgan T, Liu J, Kuokkanen PT, Carr CE, Wagner H, Kempter R. eLife 6: e26106, 2017). To determine how much the postsynaptic NL neurons contributed to the neurophonic, we recorded EFP responses in NL in vivo. Power spectral analyses showed that a small spectral component of the evoked response, between 200 and 700 Hz, could be attributed to the NL neurons' spikes, while nucleus magnocellularis (NM) spikes dominate the EFP at frequencies ≳1 kHz. Thus, spikes of NL neurons and NM axons contribute to the EFP in NL in distinct frequency bands. We conclude that if the spectral components of source types are different and if their activities can be selectively modulated, the identification of EFP sources is possible. NEW & NOTEWORTHY Extracellular field potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl's nucleus laminaris. There the EFP originates predominantly from spiking in the afferent axons, with spectral power ≳1 kHz, while postsynaptic laminaris neurons contribute little. In conclusion, the identification of EFP sources is possible if they have different spectral components and if their activities can be modulated selectively.

Physiological models of the lateral superior olive.

In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD), which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO) in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones ('shot-noise' models) to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type). These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1) that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2) that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal nonlinear processes play important roles, and (3) that, for general purposes, intermediate models might be a reasonable compromise between simplicity and biological plausibility.

Tonotopic Optimization for Temporal Processing in the Cochlear Nucleus.

UNLABELLED: In the auditory system, sounds are processed in parallel frequency-tuned circuits, beginning in the cochlea. Auditory nerve fibers reflect this tonotopy and encode temporal properties of acoustic stimuli by "locking" discharges to a particular stimulus phase. However, physiological constraints on phase-locking depend on stimulus frequency. Interestingly, low characteristic frequency (LCF) neurons in the cochlear nucleus improve phase-locking precision relative to their auditory nerve inputs. This is proposed to arise through synaptic integration, but the postsynaptic membrane's selectivity for varying levels of synaptic convergence is poorly understood. The chick cochlear nucleus, nucleus magnocellularis (NM), exhibits tonotopic distribution of both input and membrane properties. LCF neurons receive many small inputs and have low input thresholds, whereas high characteristic frequency (HCF) neurons receive few, large synapses and require larger currents to spike. NM therefore presents an opportunity to study how small membrane variations interact with a systematic topographic gradient of synaptic inputs. We investigated membrane input selectivity and observed that HCF neurons preferentially select faster input than their LCF counterparts, and that this preference is tolerant of changes to membrane voltage. We then used computational models to probe which properties are crucial to phase-locking. The model predicted that the optimal arrangement of synaptic and membrane properties for phase-locking is specific to stimulus frequency and that the tonotopic distribution of input number and membrane excitability in NM closely tracks a stimulus-defined optimum. These findings were then confirmed physiologically with dynamic-clamp simulations of inputs to NM neurons. SIGNIFICANCE STATEMENT: One way that neurons represent temporal information is by phase-locking, which is discharging in response to a particular phase of the stimulus waveform. In the auditory system, central neurons are optimized to retain or improve phase-locking precision compared with input from the auditory nerve. However, the difficulty of this computation varies systematically with stimulus frequency. We examined properties that contribute to temporal processing both physiologically and in a computational model. Neurons processing low-frequency input benefit from integration of many weak inputs, whereas those processing higher frequencies progressively lose precision by integration of multiple inputs. Here, we reveal general features of input-output optimization that apply to all neurons that process time varying input.

Roles for Coincidence Detection in Coding Amplitude-Modulated Sounds.

Many sensory neurons encode temporal information by detecting coincident arrivals of synaptic inputs. In the mammalian auditory brainstem, binaural neurons of the medial superior olive (MSO) are known to act as coincidence detectors, whereas in the lateral superior olive (LSO) roles of coincidence detection have remained unclear. LSO neurons receive excitatory and inhibitory inputs driven by ipsilateral and contralateral acoustic stimuli, respectively, and vary their output spike rates according to interaural level differences. In addition, LSO neurons are also sensitive to binaural phase differences of low-frequency tones and envelopes of amplitude-modulated (AM) sounds. Previous physiological recordings in vivo found considerable variations in monaural AM-tuning across neurons. To investigate the underlying mechanisms of the observed temporal tuning properties of LSO and their sources of variability, we used a simple coincidence counting model and examined how specific parameters of coincidence detection affect monaural and binaural AM coding. Spike rates and phase-locking of evoked excitatory and spontaneous inhibitory inputs had only minor effects on LSO output to monaural AM inputs. In contrast, the coincidence threshold of the model neuron affected both the overall spike rates and the half-peak positions of the AM-tuning curve, whereas the width of the coincidence window merely influenced the output spike rates. The duration of the refractory period affected only the low-frequency portion of the monaural AM-tuning curve. Unlike monaural AM coding, temporal factors, such as the coincidence window and the effective duration of inhibition, played a major role in determining the trough positions of simulated binaural phase-response curves. In addition, empirically-observed level-dependence of binaural phase-coding was reproduced in the framework of our minimalistic coincidence counting model. These modeling results suggest that coincidence detection of excitatory and inhibitory synaptic inputs is essential for LSO neurons to encode both monaural and binaural AM sounds.

The Role of Conduction Delay in Creating Sensitivity to Interaural Time Differences.

Axons from the nucleus magnocellularis (NM) and their targets in nucleus laminaris (NL) form the circuit responsible for encoding interaural time difference (ITD). In barn owls, NL receives bilateral inputs from NM, such that axons from the ipsilateral NM enter NL dorsally, while contralateral axons enter from the ventral side. These afferents act as delay lines to create maps of ITD in NL. Since delay-line inputs are characterized by a precise latency to auditory stimulation, but the postsynaptic coincidence detectors respond to ongoing phase difference, we asked whether the latencies of a local group of axons were identical, or varied by multiples of the inverse of the frequency they respond to, i.e., to multiples of 2π phase. Intracellular recordings from NM axons were used to measure delay-line latencies in NL. Systematic shifts in conduction delay within NL accounted for the maps of ITD, but recorded latencies of individual inputs at nearby locations could vary by 2π or 4π. Therefore microsecond precision is achieved through sensitivity to phase delays, rather than absolute latencies. We propose that the auditory system "coarsely" matches ipsilateral and contralateral latencies using physical delay lines, so that inputs arrive at NL at about the same time, and then "finely" matches latency modulo 2π to achieve microsecond ITD precision.

A comparative study of seven human cochlear filter models.

Auditory models have been developed for decades to simulate characteristics of the human auditory system, but it is often unknown how well auditory models compare to each other or perform in tasks they were not primarily designed for. This study systematically analyzes predictions of seven publicly-available cochlear filter models in response to a fixed set of stimuli to assess their capabilities of reproducing key aspects of human cochlear mechanics. The following features were assessed at frequencies of 0.5, 1, 2, 4, and 8 kHz: cochlear excitation patterns, nonlinear response growth, frequency selectivity, group delays, signal-in-noise processing, and amplitude modulation representation. For each task, the simulations were compared to available physiological data recorded in guinea pigs and gerbils as well as to human psychoacoustics data. The presented results provide application-oriented users with comprehensive information on the advantages, limitations and computation costs of these seven mainstream cochlear filter models.

Maps of interaural delay in the owl's nucleus laminaris.

Axons from the nucleus magnocellularis form a presynaptic map of interaural time differences (ITDs) in the nucleus laminaris (NL). These inputs generate a field potential that varies systematically with recording position and can be used to measure the map of ITDs. In the barn owl, the representation of best ITD shifts with mediolateral position in NL, so as to form continuous, smoothly overlapping maps of ITD with iso-ITD contours that are not parallel to the NL border. Frontal space (0°) is, however, represented throughout and thus overrepresented with respect to the periphery. Measurements of presynaptic conduction delay, combined with a model of delay line conduction velocity, reveal that conduction delays can account for the mediolateral shifts in the map of ITD.

Integrate-and-fire-type models of the lateral superior olive.

Neurons of the lateral superior olive (LSO) in the auditory brainstem play a fundamental role in binaural sound localization. Previous theoretical studies developed various types of neuronal models to study the physiological functions of the LSO. These models were usually tuned to a small set of physiological data with specific aims in mind. Therefore, it is unclear whether and how they can be related to each other, how widely applicable they are, and which model is suitable for what purposes. In this study, we address these questions for six different single-compartment integrate-and-fire (IF) type LSO models. The models are divided into two groups depending on their subthreshold responses: passive (linear) models with only the leak conductance and active (nonlinear) models with an additional low-voltage-activated potassium conductance that is prevalent among the auditory system. Each of these two groups is further subdivided into three subtypes according to the spike generation mechanism: one with simple threshold-crossing detection and voltage reset, one with threshold-crossing detection plus a current to mimic spike shapes, and one with a depolarizing exponential current for spiking. In our simulations, all six models were driven by identical synaptic inputs and calibrated with common criteria for binaural tuning. The resulting spike rates of the passive models were higher for intensive inputs and lower for temporally structured inputs than those of the active models, confirming the active function of the potassium current. Within each passive or active group, the simulated responses resembled each other, regardless of the spike generation types. These results, in combination with the analysis of computational costs, indicate that an active IF model is more suitable than a passive model for accurately reproducing temporal coding of LSO. The simulation of realistic spike shapes with an extended spiking mechanism added relatively small computational costs.

Linear summation in the barn owl's brainstem underlies responses to interaural time differences.

The neurophonic potential is a synchronized frequency-following extracellular field potential that can be recorded in the nucleus laminaris (NL) in the brainstem of the barn owl. Putative generators of the neurophonic are the afferent axons from the nucleus magnocellularis, synapses onto NL neurons, and spikes of NL neurons. The outputs of NL, i.e., action potentials of NL neurons, are only weakly represented in the neurophonic. Instead, the inputs to NL, i.e., afferent axons and their synaptic potentials, are the predominant origin of the neurophonic (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274-2290, 2010). Thus in NL the monaural inputs from the two brain sides converge and create a binaural neurophonic. If these monaural inputs contribute independently to the extracellular field, the response to binaural stimulation can be predicted from the sum of the responses to ipsi- and contralateral stimulation. We found that a linear summation model explains the dependence of the responses on interaural time difference as measured experimentally with binaural stimulation. The fit between model predictions and data was excellent, even without taking into account the nonlinear responses of NL coincidence detector neurons, although their firing rate and synchrony strongly depend on the interaural time difference. These results are consistent with the view that the afferent axons and their synaptic potentials in NL are the primary origin of the neurophonic.

Maps of ITD in the nucleus laminaris of the barn owl.

Axons from the nucleus magnocellularis (NM) and their targets in nucleus laminaris (NL) form the circuit responsible for encoding interaural time differences (ITDs). In barn owls, NL receives bilateral inputs from NM such that axons from the ipsilateral NM enter NL dorsally, while contralateral axons enter from the ventral side. These afferents and their synapses on NL neurons generate a tone-induced local field potential, or neurophonic, that varies systematically with position in NL. From dorsal to ventral within the nucleus, the best interaural time difference (ITD) of the neurophonic shifts from contralateral space to best ITDs around 0 µs. Earlier recordings suggested that in NL, iso-delay contours ran parallel to the dorsal and ventral borders of NL (Sullivan WE, Konishi M. Proc Natl Acad Sci U S A 83:8400-8404, 1986). This axis is orthogonal to that seen in chicken NL, where a single map of ITD runs from around 0 µs ITD medially to contralateral space laterally (Köppl C, Carr CE. Biol Cyber 98:541-559, 2008). Yet the trajectories of the NM axons are similar in owl and chicken (Seidl AH, Rubel EW, Harris DM, J Neurosci 30:70-80, 2010). We therefore used clicks to measure conduction time in NL and made lesions to mark the 0 µs iso-delay contour in multiple penetrations along an isofrequency slab. Iso-delay contours were not parallel to the dorsal and ventral borders of NL; instead the 0 µs iso-delay contour shifted systematically from a dorsal position in medial NL to a ventral position in lateral NL. Could different conduction delays account for the mediolateral shift in the representation of 0 µs ITD? We measured conduction delays using the neurophonic potential and developed a simple linear model of the delay-line conduction velocity. We then raised young owls with time-delaying earplugs in one ear (Gold JI, Knudsen EI, J Neurophysiol 82:2197-2209, 1999) to examine map plasticity.

Experience-Dependent Plasticity in Nucleus Laminaris of the Barn Owl.

Barn owls experience increasing interaural time differences (ITDs) during development, because their head width more than doubles in the month after hatching. We therefore hypothesized that their ITD detection circuit might be modified by experience. To test this, we raised owls with unilateral ear inserts that delayed and attenuated the acoustic signal, then measured the ITD representation in the brainstem nucleus laminaris (NL) when they were adult. The ITD circuit is composed of delay line inputs to coincidence detectors, and we predicted that plastic changes would lead to shorter delays in the axons from the manipulated ear, and complementary shifts in ITD representation on the two sides. In owls that received ear inserts starting around P14, the maps of ITD shifted in the predicted direction, but only on the ipsilateral side, and only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. The contralateral map did not change. Experience-dependent plasticity of the ITD circuit occurs in NL, and our data suggest that ipsilateral and contralateral delays are independently regulated. Thus, altered auditory input during development leads to long-lasting changes in the representation of ITD.

Computation of interaural time difference in the owl's coincidence detector neurons.

Both the mammalian and avian auditory systems localize sound sources by computing the interaural time difference (ITD) with submillisecond accuracy. The neural circuits for this computation in birds consist of axonal delay lines and coincidence detector neurons. Here, we report the first in vivo intracellular recordings from coincidence detectors in the nucleus laminaris of barn owls. Binaural tonal stimuli induced sustained depolarizations (DC) and oscillating potentials whose waveforms reflected the stimulus. The amplitude of this sound analog potential (SAP) varied with ITD, whereas DC potentials did not. The amplitude of the SAP was correlated with firing rate in a linear fashion. Spike shape, synaptic noise, the amplitude of SAP, and responsiveness to current pulses differed between cells at different frequencies, suggesting an optimization strategy for sensing sound signals in neurons tuned to different frequencies.

Signal-to-noise ratio in the membrane potential of the owl's auditory coincidence detectors.

Owls use interaural time differences (ITDs) to locate a sound source. They compute ITD in a specialized neural circuit that consists of axonal delay lines from the cochlear nucleus magnocellularis (NM) and coincidence detectors in the nucleus laminaris (NL). Recent physiological recordings have shown that tonal stimuli induce oscillatory membrane potentials in NL neurons (Funabiki K, Ashida G, Konishi M. J Neurosci 31: 15245-15256, 2011). The amplitude of these oscillations varies with ITD and is strongly correlated to the firing rate. The oscillation, termed the sound analog potential, has the same frequency as the stimulus tone and is presumed to originate from phase-locked synaptic inputs from NM fibers. To investigate how these oscillatory membrane potentials are generated, we applied recently developed signal-to-noise ratio (SNR) analysis techniques (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274-2290, 2010) to the intracellular waveforms obtained in vivo. Our theoretical prediction of the band-limited SNRs agreed with experimental data for mid- to high-frequency (>2 kHz) NL neurons. For low-frequency (≤2 kHz) NL neurons, however, measured SNRs were lower than theoretical predictions. These results suggest that the number of independent NM fibers converging onto each NL neuron and/or the population-averaged degree of phase-locking of the NM fibers could be significantly smaller in the low-frequency NL region than estimated for higher best-frequency NL.