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Pena, J. L.

Publications and source records attributed to Pena, J. L..

6 recordsLinked to original sources

MASCAF: a Cable Model Fitting Pipeline for Topologically Complex Surface Meshes

We present a free and open-source, semi-automated, topologically robust pipeline for fitting cable models to 3D surface mesh morphology data of neuronal membranes, particularly suited to structures with complex shapes and topological holes. The motivation for this work is the discovery of morphologically complex neural spines on the auditory space-specific neurons of the barn owl (Tyto alba, Tyto furcata), dubbed "toric spines", notable for their high curvature, branching density, and holes/loops. Multicompartmental simulation software requires morphology to be represented as cable models (e.g., SWC format), yet existing software tools for fitting cable models to complex 3D surface meshes have not produced satisfactory results for toric spines, and loops are generally unsupported. We present the Mesh and Skeleton Cable Fitting (MASCAF) pipeline and software, which fits a cable model (e.g., SWC format) to a surface mesh using mean-curvature flow skeletonization. In this paper, we demonstrate how MASCAF is applied to fit cable models, how loops can be reconstructed in simulations with the Arbor and NEURON simulation software, and how the results can be validated using geometry and simulator-based methods. While non-tree morphologies such as toric spines are neuroanatomically special, our software pipeline provides a cable-model fitting approach for surface mesh data that is topologically robust, deterministic, open-source, and applicable to general morphologies, thereby closing a crucial gap between neuronal imaging and high-resolution simulation.

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A flexible cross-correlation based population model of interaural time difference coding in barn owl's midbrain

The cross-correlation model has long served as the standard computational framework for describing interaural time difference (ITD) processing in the barn owls auditory system. While successful in explaining initial sinusoidal responses at the site of coincidence detection in the nucleus laminaris, this previous standard model fails to capture the full diversity of ITD tuning observed in the inferior colliculus (IC), where neurons exhibit sharper-than-sinusoidal ITD tuning, nonlinear frequency integration, level-dependent gain control, and interaural level difference (ILD)-dependent modulation of ITD selectivity. Here we present a modified cross-correlation model that addresses these limitations through the addition of parameterized gain control, linear filters with inhibitory surround structure, static nonlinearities, and ILD-dependent modulation of the cross-correlation computation. We show that divisive gain control produces realistic rate-level functions, including non-monotonic responses. Furthermore, inhibitory weights in the linear filter, combined with a threshold or expansive nonlinearity, generate sharper-than-sinusoidal ITD tuning consistent with experimental observations. This model reproduces both linear and nonlinear two-tone frequency integration and demonstrates that independent variation of filter bandwidth and nonlinearity shape accounts for the experimentally observed lack of correlation between side-peak suppression and frequency tuning width across the neuronal population. In addition, ILD-dependent modifications to the model produce shifts in best ITD and reductions in ITD tuning strength, as observed in the lateral shell of the central nucleus of the IC. The model parameters can be efficiently determined using simulation-based inference, enabling generation of realistic neuronal populations. Thus, this flexible, analytically tractable framework provides a foundation for investigating population coding of auditory space in the owls midbrain.

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Neural responses underlying ITD discrimination as a function of sensory reliability in the barn owl

Discrimination of sensory stimuli is fundamentally constrained by the information encoded in neuronal responses. In the barn owl, interaural time difference (ITD) serves as a primary cue for azimuthal sound localization and is represented topographically in the midbrain auditory space map in the external nucleus of the inferior colliculus (ICx). While prior studies have demonstrated a correspondence between spatial tuning and behavioral acuity, it remains unclear how changes in sensory reliability influence this relationship. Here, we examined how behavioral and neuronal ITD discrimination thresholds vary with binaural correlation (BC), which manipulates ITD cue reliability. Using the pupil dilation response (PDR) as a behavioral metric in head-fixed owls, we found that ITD just-noticeable-differences increased exponentially as BC decreased. In contrast, the widths of ICx ITD tuning curves increased more modestly, indicating that tuning resolution alone does not account for behavioral discrimination performance. By computing the Fisher information from ICx neuronal responses, we showed that the average neuronal discriminability predicts behavioral thresholds across BC levels. A habituation-based model incorporating BC-dependent changes in tuning width, firing rate, and response variability successfully accounted for both direction and ITD discrimination. These findings support a model in which perceptual acuity is governed by the combined influence of neuronal tuning and variability and provide a unified framework for understanding how midbrain auditory representations underlie adaptive spatial hearing.

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Sufficiency of ITD for (biased) human auditory azimuthal perception

Experiments on human auditory perception have shown that interaural time difference (ITD) is sufficient to generate spatial percepts, even though stimuli containing only the ITD cue are perceived as being emitted from inside the head instead of from external locations at specific azimuths. These experiments are thus interpreted as "lateralization" instead of "localization" tasks. In fact, lateralized spatial perception has been quantified using tasks in which participants have to report their estimates by selecting a putative location inside the head, or matching the perceived position to sounds with a given interaural level difference. Therefore, these estimates are made with respect to internal frames of reference, but it is unclear whether these percepts have any significance for the more ecological problem of locating an external sound source. In order to investigate the link between internalized spatial percepts and sound localization, we designed a new task in which subjects are instructed to report externalized azimuthal location for sounds containing only ITD cues. Despite the mismatch between an internalized percept having to be reported as emanating from an external location, subjects were able to estimate azimuths consistently. Furthermore, normalized estimates were indistinguishable from those obtained using traditional lateralization tasks. Our results revealed a direct relationship between perceived azimuths and ITD, which deviates from that obtained from acoustical analysis of binaural recordings, revealing estimation biases. Intriguingly, these results indicate that externalized percepts are not required for the generation of azimuthal percepts.

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Development shaped by cue reliability in the barn owl's auditory midbrain

Sensory systems display capability to preferentially choose stimuli based on their reliability at conveying accurate information. While previous reports have shown the ability of the brain to reweigh cues based on ongoing or dynamic changes in reliability, how the brain may learn and maintain neural responses to sensory statistics expected to be stable over longer time periods remain significant open questions of potential mechanisms underlying naturalistic biased perception. This study provides evidence that the barn owls midbrain is shaped by permanent statistics experienced during development. The barn owls midbrain features a topographic map of auditory space where neurons compute horizontal sound location from the interaural time difference (ITD). Previous work has shown that frequency tuning of these midbrain map neurons is correlated with the pattern of most reliable frequencies for the neurons preferred ITD. This pattern of ITD reliability is due to the filtering properties of the head, primarily determined by the facial ruff in the barn owl. In this study, we found that the absence of a facial ruff led to a decrease in the reliability of high frequencies originating from frontal space. To test if the owls frequency tuning of midbrain map neurons is driven by permanent changes in the pattern of ITD reliability, these neurons were recorded from adult owls, who had the facial ruff removed as juveniles, and from juvenile owls, before the facial ruff developed. In both groups, we found that frontally-tuned neurons displayed tunings to frequencies lower than reported in normal adult owls, consistent with the difference in ITD reliability between the normal and ruff removed conditions. Juvenile owls also exhibited more heterogeneous frequency tuning, suggesting developmental processes that refine tuning to match the pattern of ITD reliability. Additional recordings immediately upstream of the midbrain map displayed ITD tuned neural responses for all frequencies across the owls normal hearing range. Broader analysis of the effects of ruff-removal on the acoustical properties of spatial cues indicated a dominant role of ITD reliability in driving the adaptive changes in frequency tuning. These results support the hypothesis that frequency tuning in the midbrain map is developmentally adapted to permanent statistics of spatial cues, implementing probabilistic coding for sound localization.

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Emergence of an adaptive command for orienting behavior in premotor brainstem neurons of barn owls

The midbrain map of auditory space commands sound-orienting responses in barn owls. Owls precisely localize sounds in frontal space but underestimate the direction of peripheral sound sources. This bias for central locations was proposed to be adaptive to the decreased reliability in the periphery of sensory cues used for sound localization by the owl. Understanding the neural pathway supporting this biased behavior provides a means to address how adaptive motor commands are implemented by neurons. Here we find that the sensory input for sound direction is weighted by its reliability in premotor neurons of the owls midbrain tegmentum such that the mean population firing rate approximates the head-orienting behavior. We provide evidence that this coding may emerge through convergence of upstream projections from the midbrain map of auditory space. We further show that manipulating the sensory input yields changes predicted by the convergent network in both premotor neural responses and behavior. This work demonstrates how a topographic sensory representation can be linearly read out to adjust behavioral responses by the reliability of the sensory input.\n\nSignificance statementThis research shows how statistics of the sensory input can be integrated into a behavioral command by readout of a sensory representation. The firing rate of midbrain premotor neurons receiving sensory information from a topographic representation of auditory space is weighted by the reliability of sensory cues. We show that these premotor responses are consistent with a weighted convergence from the topographic sensory representation. This convergence was also tested behaviorally, where manipulation of stimulus properties led to bidirectional changes in sound localization errors. Thus a topographic representation of auditory space is translated into a premotor command for sound localization that is modulated by sensory reliability.

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