A nonneural miRNA cluster mediates hearing via repression of two neural targets.

We show here that mir-279/996 are absolutely essential for development and function of Johnston's organ (JO), the primary proprioceptive and auditory organ in Drosophila Their deletion results in highly aberrant cell fate determination, including loss of scolopale cells and ectopic neurons, and mutants are electrophysiologically deaf. In vivo activity sensors and mosaic analyses indicate that these seed-related miRNAs function autonomously to suppress neural fate in nonneuronal cells. Finally, genetic interactions pinpoint two neural targets (elav and insensible) that underlie miRNA mutant JO phenotypes. This work uncovers how critical post-transcriptional regulation of specific miRNA targets governs cell specification and function of the auditory system.

Acoustic Pattern Recognition and Courtship Songs: Insights from Insects.

Across the animal kingdom, social interactions rely on sound production and perception. From simple cricket chirps to more elaborate bird songs, animals go to great lengths to communicate information critical for reproduction and survival via acoustic signals. Insects produce a wide array of songs to attract a mate, and the intended receivers must differentiate these calls from competing sounds, analyze the quality of the sender from spectrotemporal signal properties, and then determine how to react. Insects use numerically simple nervous systems to analyze and respond to courtship songs, making them ideal model systems for uncovering the neural mechanisms underlying acoustic pattern recognition. We highlight here how the combination of behavioral studies and neural recordings in three groups of insects-crickets, grasshoppers, and fruit flies-reveals common strategies for extracting ethologically relevant information from acoustic patterns and how these findings might translate to other systems.

Distinct early and late neural mechanisms regulate feature-specific sensory adaptation in the human visual system.

A canonical feature of sensory systems is that they adapt to prolonged or repeated inputs, suggesting the brain encodes the temporal context in which stimuli are embedded. Sensory adaptation has been observed in the central nervous systems of many animal species, using techniques sensitive to a broad range of spatiotemporal scales of neural activity. Two competing models have been proposed to account for the phenomenon. One assumes that adaptation reflects reduced neuronal sensitivity to sensory inputs over time (the "fatigue" account); the other posits that adaptation arises due to increased neuronal selectivity (the "sharpening" account). To adjudicate between these accounts, we exploited the well-known "tilt aftereffect", which reflects adaptation to orientation information in visual stimuli. We recorded whole-brain activity with millisecond precision from human observers as they viewed oriented gratings before and after adaptation, and used inverted encoding modeling to characterize feature-specific neural responses. We found that both fatigue and sharpening mechanisms contribute to the tilt aftereffect, but that they operate at different points in the sensory processing cascade to produce qualitatively distinct outcomes. Specifically, fatigue operates during the initial stages of processing, consistent with tonic inhibition of feedforward responses, whereas sharpening occurs ~200 ms later, consistent with feedback or local recurrent activity. Our findings reconcile two major accounts of sensory adaptation, and reveal how this canonical process optimizes the detection of change in sensory inputs through efficient neural coding.

Human stem cell models to study placode development, function and pathology.

Placodes are embryonic structures originating from the rostral ectoderm that give rise to highly diverse organs and tissues, comprising the anterior pituitary gland, paired sense organs and cranial sensory ganglia. Their development, including the underlying gene regulatory networks and signalling pathways, have been for the most part characterised in animal models. In this Review, we describe how placode development can be recapitulated by the differentiation of human pluripotent stem cells towards placode progenitors and their derivatives, highlighting the value of this highly scalable platform as an optimal in vitro tool to study the development of human placodes, and identify human-specific mechanisms in their development, function and pathology.

Valence opponency in peripheral olfactory processing.

A hallmark of complex sensory systems is the organization of neurons into functionally meaningful maps, which allow for comparison and contrast of parallel inputs via lateral inhibition. However, it is unclear whether such a map exists in olfaction. Here, we address this question by determining the organizing principle underlying the stereotyped pairing of olfactory receptor neurons (ORNs) in Drosophila sensory hairs, wherein compartmentalized neurons inhibit each other via ephaptic coupling. Systematic behavioral assays reveal that most paired ORNs antagonistically regulate the same type of behavior. Such valence opponency is relevant in critical behavioral contexts including place preference, egg laying, and courtship. Odor-mixture experiments show that ephaptic inhibition provides a peripheral means for evaluating and shaping countervailing cues relayed to higher brain centers. Furthermore, computational modeling suggests that this organization likely contributes to processing ratio information in odor mixtures. This olfactory valence map may have evolved to swiftly process ethologically meaningful odor blends without involving costly synaptic computation.

The Clathrin adaptor AP-1 and Stratum act in parallel pathways to control Notch activation in Drosophila sensory organ precursors cells.

Drosophila sensory organ precursors divide asymmetrically to generate pIIa/pIIb cells, the identity of which relies on activation of Notch at cytokinesis. Although Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, the basal pool of Notch is reported to be the main contributor for Notch activation in the pIIa cell. Intra-lineage signalling requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We have previously reported that AP-1 and Stratum regulate the trafficking of Notch and Sanpodo from the trans-Golgi network to the basolateral membrane. Loss of AP-1 or Stratum caused mild Notch gain-of-function phenotypes. Here, we report that their concomitant loss results in a penetrant Notch gain-of-function phenotype, indicating that they control parallel pathways. Although unequal partitioning of cell fate determinants and cell polarity were unaffected, we observed increased amounts of signalling-competent Notch as well as Delta and Sanpodo at the apical pIIa-pIIb interface, at the expense of the basal pool of Notch. We propose that AP-1 and Stratum operate in parallel pathways to localize Notch and control where receptor activation takes place.

Remodelling the inguinal adipose sensory system to switch on the furnace: Electroacupuncture stimulation induces brown adipose thermogenesis.

Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, ß3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.

Neuromorphic Gustatory System with Salt-Taste Perception, Information Processing, and Excessive-Intake Warning Capabilities.

Emulation of the process of a biological gustatory system could benefit the reconstruction of sense of taste. Here we demonstrate the first neuromorphic gustatory system that emulates the ability of taste perception, information processing, and excessive-intake warning functions. The system integrates a chitosan-derived ion-gel sensor, SnO2 nanowire artificial synapses, and an effect-executive unit. The system accomplish perception and encoding behaviors for taste stimulation without using complex circuits and multivariate analysis, showing short response delay (<1 s), long taste memory duration (>2 h), and a wide perceptive concentration range (0.02-6 wt % salt solution). Especially, SnO2 NW artificial synapses have extremely small response voltage (1 mV), exceeding the biological level by orders of magnitude, representing so-far the highest sensitivity record. This work provides a promising strategy to develop bioinspired and biointegrated electronics with the intention of mimicking and restoring the functions of biological sensory systems.

Gross morphology of the brain and some sense organs of subterranean pencil catfishes of the genus Ituglanis Costa and Bockmann, 1993 (Siluriformes, Trichomycteridae), with a discussion on sensory compensation versus preadaptation in subterranean fishes.

Subterranean organisms provide excellent opportunities to investigate morphological evolution, especially of sensory organs and structures and their processing areas in the central nervous system. We describe the gross morphology of the brain and some cephalic sensory organs (olfactory organ, eye, semicircular canals of the inner ear) and the swim bladder (a non-sensory accessory structure) of subterranean species of pencil catfishes of the genus Ituglanis Costa and Bockmann, 1993 (Siluriformes, Trichomycteridae) and compare them with an epigean species of the genus, Ituglanis goya Datovo, Aquino and Langeani, 2016. We compared qualitatively the size of the different brain regions and sense organs of the subterranean species with those of the epigean one, searching for modifications possibly associated with living in the subterranean environment. Our findings suggest that species of Ituglanis exhibit sensory characteristics that are preadaptive for the subterranean life, as only slight modifications were observed in the brains and sense organs of the subterranean species of the genus when compared with the epigean one. Because most subterranean fish species belong to lineages putatively preadapted for subterranean life, our results, discussed in the context of available information on the brain and sense organs of other subterranean species, help identify general trends for the evolution of the brain and sensory organs of subterranean fishes in general.

Wiring the senses: Factors that regulate peripheral axon pathfinding in sensory systems.

Sensory neurons of the head are the ones that transmit the information about the external world to our brain for its processing. Axons from cranial sensory neurons sense different chemoattractant and chemorepulsive molecules during the journey and in the target tissue to establish the precise innervation with brain neurons and/or receptor cells. Here, we aim to unify and summarize the available information regarding molecular mechanisms guiding the different afferent sensory axons of the head. By putting the information together, we find the use of similar guidance cues in different sensory systems but in distinct combinations. In vertebrates, the number of genes in each family of guidance cues has suffered a great expansion in the genome, providing redundancy, and robustness. We also discuss recently published data involving the role of glia and mechanical forces in shaping the axon paths. Finally, we highlight the remaining questions to be addressed in the field.

Neuroplastic changes in functional wiring in sensory cortices of the congenitally deaf: A network analysis.

Congenital sensory deprivation induces significant changes in the structural and functional organisation of the brain. These are well-characterised by cross-modal plasticity, in which deprived cortical areas are recruited to process information from non-affected sensory modalities, as well as by other neuroplastic alterations within regions dedicated to the remaining senses. Here, we analysed visual and auditory networks of congenitally deaf and hearing individuals during different visual tasks to assess changes in network community structure and connectivity patterns due to congenital deafness. In the hearing group, the nodes are clearly divided into three communities (visual, auditory and subcortical), whereas in the deaf group a fourth community consisting mainly of bilateral superior temporal sulcus and temporo-insular regions is present. Perhaps more importantly, the right lateral geniculate body, as well as bilateral thalamus and pulvinar joined the auditory community of the deaf. Moreover, there is stronger connectivity between bilateral thalamic and pulvinar and auditory areas in the deaf group, when compared to the hearing group. No differences were found in the number of connections of these nodes to visual areas. Our findings reveal substantial neuroplastic changes occurring within the auditory and visual networks caused by deafness, emphasising the dynamic nature of the sensory systems in response to congenital deafness. Specifically, these results indicate that in the deaf but not the hearing group, subcortical thalamic nuclei are highly connected to auditory areas during processing of visual information, suggesting that these relay areas may be responsible for rerouting visual information to the auditory cortex under congenital deafness.

Stimulator compensation and generation of Gaussian noise stimuli with defined amplitude spectra for studying input-output relations of sensory systems.

Gaussian noise is an important stimulus for the study of biological systems, especially sensory and neural systems. Since these systems are inherently nonlinear, the properties of the noise strongly influence the outcome of the analysis. Therefore, it is crucial to use a well-defined and controlled noise stimulus. In this paper, we first use the example of an insect filiform sensillum, a simple mechanoreceptor with a single sensory cell, to show that changes in the amplitude and spectral properties of the noise stimulus indeed affect the linear transfer function of the sensillum. We then explain step-by-step how to use the inverse fast Fourier transform to generate a Gaussian noise that has an arbitrary user-defined amplitude spectrum, including a band-limited white noise with a perfectly sharp cutoff edge. Finally, we demonstrate how such a perfect band-limited Gaussian white noise stimulus can also be generated with a non-perfect stimulator using a simple procedure that compensates for the filtering properties of the stimulator. With this approach, one can generate well-defined Gaussian noise stimuli that can be adapted to any application. For example, one can generate visual, sound, or vibrational stimuli for experimental research in visual physiology, auditory physiology, and biotremology, as well as inputs for testing various models in theoretical research.

Active smelling in the American cockroach.

Motion plays an essential role in sensory acquisition. From changing the position in which information can be acquired to fine-scale probing and active sensing, animals actively control the way they interact with the environment. In olfaction, movement impacts the time and location of odour sampling as well as the flow of odour molecules around the olfactory organs. Employing a detailed spatiotemporal analysis, we investigated how insect antennae interact with the olfactory environment in a species with a well-studied olfactory system - the American cockroach. Cockroaches were tested in a wind-tunnel setup during the presentation of odours with different attractivity levels: colony extract, butanol and linalool. Our analysis revealed significant changes in antennal kinematics when odours were presented, including a shift towards the stream position, an increase in vertical movement and high-frequency local oscillations. Nevertheless, the antennal shifting occurred predominantly in a single antenna while the overall range covered by both antennae was maintained throughout. These findings hold true for both static and moving stimuli and were more pronounced for attractive odours. Furthermore, we found that upon odour encounter, there was an increase in the occurrence of high-frequency antennal sweeps and vertical strokes, which were shown to impact the olfactory environment's statistics directly. Our study lays out a tractable system for exploring the tight coupling between sensing and movement, in which antennal sweeps, in parallel to mammalian sniffing, are actively involved in facilitating odour capture and transport, generating odour intermittency in environments with low air movement where cockroaches dwell.

Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead. Cognition and Sensory Systems in Healthy and Diseased Subjects.

This article summarizes selected presentations from a session titled "Cognition and Sensory Systems in Healthy and Diseased Subjects", held to highlight and honor the work of Dr. Marilyn Jones-Gotman. The session was part of a two-day symposium, "Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead". The session presented research on epilepsy and sensory systems by colleagues and former trainees of Dr. Jones-Gotman. The extended summaries provide an overview of historical and current work in the neuropsychology of epilepsy, neuropsychological and neuroimaging approaches to understanding brain organization, sex differences in brain mechanisms underlying neurological disorders, dietary influences on brain function and cognition, and expertise in olfactory training and language experiences and their implications for brain organization and structure.

Invited review - the effects of anthropogenic abiotic stressors on the sensory systems of fishes.

Climate change is a growing global issue with many countries and institutions declaring a climate state of emergency. Excess CO2 from anthropogenic sources and changes in land use practices are contributing to many detrimental changes, including increased global temperatures, ocean acidification and hypoxic zones along coastal habitats. All senses are important for aquatic animals, as it is how they can perceive and respond to their environment. Some of these environmental challenges have been shown to impair their sensory systems, including the olfactory, visual, and auditory systems. While most of the research is focused on how ocean acidification affects olfaction, there is also evidence that it negatively affects vision and hearing. The effects that temperature and hypoxia have on the senses have also been investigated, but to a much lesser extent in comparison to ocean acidification. This review assembles the known information on how these anthropogenic challenges affect the sensory systems of fishes, but also highlights what gaps in knowledge remain with suggestions for immediate action. Olfaction, vision, otolith, pH, freshwater, seawater, marine, central nervous system, electrophysiology, mechanism.

Evolution of left-right asymmetry in the sensory system and foraging behavior during adaptation to food-sparse cave environments.

BACKGROUND: Laterality in relation to behavior and sensory systems is found commonly in a variety of animal taxa. Despite the advantages conferred by laterality (e.g., the startle response and complex motor activities), little is known about the evolution of laterality and its plasticity in response to ecological demands. In the present study, a comparative study model, the Mexican tetra (Astyanax mexicanus), composed of two morphotypes, i.e., riverine surface fish and cave-dwelling cavefish, was used to address the relationship between environment and laterality. RESULTS: The use of a machine learning-based fish posture detection system and sensory ablation revealed that the left cranial lateral line significantly supports one type of foraging behavior, i.e., vibration attraction behavior, in one cave population. Additionally, left-right asymmetric approaches toward a vibrating rod became symmetrical after fasting in one cave population but not in the other populations. CONCLUSION: Based on these findings, we propose a model explaining how the observed sensory laterality and behavioral shift could help adaptation in terms of the tradeoff in energy gain and loss during foraging according to differences in food availability among caves.

An Optical Sensory System for Assessment of Residual Cancer Burden in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Breast cancer patients undergoing neoadjuvant chemotherapy (NAC) require precise and accurate evaluation of treatment response. Residual cancer burden (RCB) is a prognostic tool widely used to estimate survival outcomes in breast cancer. In this study, we introduced a machine-learning-based optical biosensor called the Opti-scan probe to assess residual cancer burden in breast cancer patients undergoing NAC. The Opti-scan probe data were acquired from 15 patients (mean age: 61.8 years) before and after each cycle of NAC. Using regression analysis with k-fold cross-validation, we calculated the optical properties of healthy and unhealthy breast tissues. The ML predictive model was trained on the optical parameter values and breast cancer imaging features obtained from the Opti-scan probe data to calculate RCB values. The results show that the ML model achieved a high accuracy of 0.98 in predicting RCB number/class based on the changes in optical properties measured by the Opti-scan probe. These findings suggest that our ML-based Opti-scan probe has considerable potential as a valuable tool for the assessment of breast cancer response after NAC and to guide treatment decisions. Therefore, it could be a promising, non-invasive, and accurate method for monitoring breast cancer patient's response to NAC.

Sex-specific evolution of a Drosophila sensory system via interacting cis- and trans-regulatory changes.

The evolution of gene expression via cis-regulatory changes is well established as a major driver of phenotypic evolution. However, relatively little is known about the influence of enhancer architecture and intergenic interactions on regulatory evolution. We address this question by examining chemosensory system evolution in Drosophila. Drosophila prolongata males show a massively increased number of chemosensory bristles compared to females and males of sibling species. This increase is driven by sex-specific transformation of ancestrally mechanosensory organs. Consistent with this phenotype, the Pox neuro transcription factor (Poxn), which specifies chemosensory bristle identity, shows expanded expression in D. prolongata males. Poxn expression is controlled by nonadditive interactions among widely dispersed enhancers. Although some D. prolongata Poxn enhancers show increased activity, the additive component of this increase is slight, suggesting that most changes in Poxn expression are due to epistatic interactions between Poxn enhancers and trans-regulatory factors. Indeed, the expansion of D. prolongata Poxn enhancer activity is only observed in cells that express doublesex (dsx), the gene that controls sexual differentiation in Drosophila and also shows increased expression in D. prolongata males due to cis-regulatory changes. Although expanded dsx expression may contribute to increased activity of D. prolongata Poxn enhancers, this interaction is not sufficient to explain the full expansion of Poxn expression, suggesting that cis-trans interactions between Poxn, dsx, and additional unknown genes are necessary to produce the derived D. prolongata phenotype. Overall, our results demonstrate the importance of epistatic gene interactions for evolution, particularly when pivotal genes have complex regulatory architecture.

Early embryonic development of Johnston's organ in the antenna of the desert locust Schistocerca gregaria.

Johnston's organ has been shown to act as an antennal auditory organ across a spectrum of insect species. In the hemimetabolous desert locust Schistocerca gregaria, Johnston's organ must be functional on hatching and so develops in the pedicellar segment of the antenna during embryogenesis. Here, we employ the epithelial cell marker Lachesin to identify the pedicellar domain of the early embryonic antenna and then triple-label against Lachesin, the mitosis marker phosphohistone-3, and neuron-specific horseradish peroxidase to reveal the sense-organ precursors for Johnston's organ and their lineages. Beginning with a single progenitor at approximately a third of embryogenesis, additional precursors subsequently appear in both the ventral and dorsal pedicellar domains, each generating a lineage or clone. Lineage locations are remarkably conserved across preparations and ages, consistent with the epithelium possessing an underlying topographic coordinate system that determines the cellular organization of Johnston's organ. By mid-embryogenesis, twelve lineages are arranged circumferentially in the pedicel as in the adult structure. Each sense-organ precursor is associated with a smaller mitotically active cell from which the neuronal complement of each clone may derive. Neuron numbers within a clone increase in discrete steps with age and are invariant between clones and across preparations of a given age. At mid-embryogenesis, each clone comprises five cells consolidated into a tightly bound cartridge. A long scolopale extends apically from each cartridge to an insertion point in the epithelium, and bundled axons project basally toward the brain. Comparative data suggest mechanisms that might also regulate the developmental program of Johnston's organ in the locust.

Exosomes in the visual system: New avenues in ocular diseases.

Exosomes are a subgroup of membrane-bound extracellular vesicles secreted by all cell types and present virtually in all biological fluids. The composition of exosomes in the same cell type varies in healthy and disease conditions. Hence, exosomes research is a prime focus area for clinical research in cancer and numerous age-related metabolic syndromes. Functions of exosomes include crucial cell-to-cell communication that mediates complex cellular processes, such as antigen presentation, stem cell differentiation, and angiogenesis. However, very few studies reported the presence and role of exosomes in normal physiological and pathological conditions of specialized ocular tissues of the eye and ocular cancers. The eye being a protected sense organ with unique connectivity with the rest of the body through the blood and natural passages, we believe that the role of exosomes in ocular tissues will significantly improve our understanding of ocular diseases and their interactions with the rest of the body. We present a review that highlights the existence and function of exosomes in various ocular tissues, their role in the progression of some of the neoplastic and non-neoplastic conditions of the eyes.