Search bioRxiv⌕ Search

bioRxiv · 10.1101/863258

Computational principles of neural adaptation for binaural signal integration

Abstract

Adaptation to statistics of sensory inputs is an essential ability of neural systems and extends their effective operational range. Having a broad operational range facilitates to react to sensory inputs of different granularities, thus is a crucial factor for survival. The computation of auditory cues for spatial localization of sound sources, particularly the interaural level difference (ILD), has long been considered as a static process. Novel findings suggest that this process of ipsi- and contra-lateral signal integration is highly adaptive and depends strongly on recent stimulus statistics. Here, adaptation aids the encoding of auditory perceptual space of various granularities. To investigate the mechanism of auditory adaptation in binaural signal integration in detail, we developed a neural model architecture for simulating functions of lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) composed of single compartment conductance-based neurons. Neurons in the MNTB serve as an intermediate relay population. Their signal is integrated by the LSO population on a circuit level to represent excitatory and inhibitory interactions of input signals. The circuit incorporates an adaptation mechanism operating at the synaptic level based on local inhibitory feedback signals. The models predictive power is demonstrated in various simulations replicating physiological data. Incorporating the innovative adaptation mechanism facilitates a shift in neural responses towards the most effective stimulus range based on recent stimulus history. The model demonstrates that a single LSO neuron quickly adapts to these stimulus statistics and, thus, can encode an extended range of ILDs in the ipsilateral hemisphere. Most significantly, we provide a unique measurement of the adaptation efficacy of LSO neurons. Prerequisite of normal function is an accurate interaction of inhibitory and excitatory signals, a precise encoding of time and a well-tuned local feedback circuit. We suggest that the mechanisms of temporal competitive-cooperative interaction and the local feedback mechanism jointly sensitize the circuit to enable a response shift towards contra-lateral and ipsi-lateral stimuli, respectively. Author summaryWhy are we more precise in localizing a sound after hearing it several times? Adaptation to the statistics of a stimulus plays a crucial role in this. The present article investigates the abilities of a neural adaptation mechanism for improved localization skills based on a neural network model. Adaptation to stimulus statistics is very prominent in sensory systems of animals and allows them to respond to a wide range of stimuli, thus is a crucial factor for survival. For example, humans are able to navigate under suddenly changing illumination conditions (driving a car into and out of a tunnel). This is possible by courtesy of adaptation abilities of our sensory organs and pathways. Certainly, adaptation is not confined to a single sense like vision but also affects other senses like audition. Especially the perception of sound source location. Compared to vision, the localization of a sound source in the horizontal plane is a rather complicated task since the location cannot be read out from the receptor surface but needs to be computed. This requires the underlying neural system to calculate differences of the intensity between the two ears which provide a distinct cue for the location of a sound source. Here, adaptation to this cue allows to focus on a specific part of auditory space and thereby facilitates improved localisation abilities. Based on recent findings that suggest that the intensity difference computation is a flexible process with distinct adaptation mechanisms, we developed a neural model that computes the intensity difference to two incoming sound signals. The model comprises a novel mechanism for adaptation to sound source locations and provides a means to investigate underlying neural principles of adaptation and compare their effectivenesses. We demonstrate that due this mechanism the perceptual range is extended and a finer resolution of auditory space is obtained. Results explain the neural basis for adaptation and indicate that the interplay between different adaptation mechanisms facilitate highly precise sound source localization in a wide range of locations.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Oess, T., Ernst, M. O., Neumann, H.. 2019-12-03. Computational principles of neural adaptation for binaural signal integration. https://doi.org/10.1101/863258

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Epidermal Langerhans Cells Act as Neuroimmune Regulators of Pain and Itch

Neuroimmune interactions in the skin coordinate immune defense and somatosensory perception, yet how immune cells shape sensory signaling remains poorly defined. Here, we show that Langerhans cells (LCs), epidermal antigen-presenting cells, function as local immune-derived amplifiers of cutaneous sensory signaling. Anatomical and transcriptomic analyses reveal preferential LC association with non-peptidergic sensory neurons. LC activation increases neuronal and behavioral responses to thermal, mechanical, and pruritic stimuli without directly exciting sensory neurons, whereas LC inhibition or ablation selectively reduces pruritogen-evoked itch. We identified semaphorin 7A as a candidate LC-expressed mediator. Semaphorin 7A sensitized cultured sensory neurons to chloroquine and histamine, and neutralizing semaphorin 7A abolished the increase in chloroquine-evoked scratching produced by LC activation. Its receptor PlexinC1 was expressed by most MrgprA3 pruriceptors and blocking PlexinC1 reduced semaphorin 7A-evoked neuronal responses. Together, these findings identify epidermal LCs as local immune-derived amplifiers that regulate the responsiveness of cutaneous sensory circuits and identify semaphorin 7A as a mediator of LC-induced itch potentiation.

neuroscience↗

Feasible closed-loop stimulation for neural latent dynamics control

Modern neuroscience benefits from powerful computational and experimental methods for studying neural populations, including latent dynamics models that predict behavior with few dimensions. But despite their explanatory utility, latent factors are seldom targeted explicitly with experimental perturbations, leaving causal relationships to behavior and inferred dynamical landscapes untested. A promising solution is closed-loop, multi-channel optogenetic control, which, when paired with model predictions, could steer neural trajectories in real time--a feat impossible for traditional, hand-designed stimulation. However, because closed-loop latent control has not been demonstrated in vivo, the hardware and software requirements remain unclear--particularly the necessary stimulation dimensionality and how limited resources such as implant volume and bandwidth should be allocated between stimulation and recording capabilities. Preliminary experiments would thus help guide ongoing technological development. As large-scale exploration of these design spaces in vivo is prohibitively expensive, we conducted a high-throughput simulation survey using biophysically grounded spiking neural networks. We found that low-dimensional actuation is sufficient: in the reference configuration, ~20% of the stimulation channels achieved ~85% of peak control performance, far fewer than the number of neurons. Furthermore, allocating channels roughly equally between stimulation and recording optimized behavioral control, whereas pairing many electrodes with a single light source--the prevailing practice in experimental labs--performed poorly. Even without heavily optimizing modeling or control, we obtained >60% tracking error reduction and >90% evoked behavior accuracy on average for optimal channel counts. These results held across extensive parameter variations, suggesting that closed-loop latent control is feasible with accessible channel counts and establishing design principles for future tool development and in vivo experiments.

neuroscience↗

Identification of Kinome Biomarkers and Therapeutic Rescue in cGMP-Linked Retinal Degeneration

Inherited retinal degenerations, such as Retinitis Pigmentosa (RP) and Leber's congenital amaurosis (LCA), are major causes of progressive and irreversible vision loss. The large number of genes associated with these disorders makes their clinical and molecular characterization difficult, while systemic biomarkers for disease progression or treatment response remain limited. These challenges were addressed by targeting cGMP-associated mechanisms shared by RP and LCA and integrating systemic biomarker profiling with retinal outcomes. Kinase activity analysis (kinome analysis) in peripheral blood mononuclear cells distinguished healthy and diseased states and captured therapy-associated signatures in rd10 mice treated with LP-CN03, a liposomal formulation of the cGMP analog CN03. This first systemic analysis in a therapeutically responsive animal model highlights kinome analysis as a potential translational readout. Given shared cGMP signaling in RP and AIPL1-associated LCA, LP-CN03's therapeutic potential was further evaluated in a new CRISPR-Cas9-generated Aipl1-/- mouse model. Treatment with LP-CN03 preserved retinal structure and function, as shown by electroretinography, longitudinal optical coherence tomography, fundus imaging, optomotor testing, and photoreceptor-specific gene expression. Together, these findings provide independent in vivo evidence for the neuroprotective effect of LP-CN03 in both cGMP-related RP and LCA, also highlighting the translational value of kinome profiling.

neuroscience↗