Sensory Systems Research Articles

Experience: A Comparative Analysis of Multivariate Time-Series Generative Models: A Case Study on Human Activity Data

Human activity recognition (HAR) is an active research field that has seen great success in recent years due to advances in sensory data collection methods and activity recognition systems. Deep artificial intelligence (AI) models have contributed to the success of HAR systems lately although still suffering from limitations such as data scarcity, the high costs of labelling data instances and datasets’ imbalance and bias. The temporal nature of human activity data, represented as time series data, impose an additional challenge to using AI models in HAR because most state-of-the-art models do not account for the time component of the data instances. These limitations have inspired the time-series research community to design generative models for sequential data but very little work has been done to evaluate the quality of such models. In this work, we conduct a comparative quality analysis of three generative models for time-series data, using a case study in which we aim to generate sensory human activity data from a seed public dataset. Additionally, we adapt and clearly explain four evaluation methods of synthetic time-series data from the literature and apply them to assess the quality of the synthetic activity data we generate. We show experimentally that high quality human activity data can be generated using deep generative models, and the synthetic data can thus be used in HAR systems to augment real activity data. We also demonstrate that the chosen evaluation methods effectively ensure that the generated data meets the essential quality benchmarks of realism, diversity, coherence and utility. Our findings suggest that using deep generative models to produce synthetic human activity data can potentially address challenges related to data scarcity, biases, and expensive labeling. This holds promise for enhancing the efficiency and reliability of HAR systems.

Conservation and selective pressures shaping baleen whale olfactory receptor genes supports their use of olfaction in the marine environment.

The relative importance of various sensory modalities can shift in response to evolutionary transitions, resulting in changes to underlying gene families encoding their reception systems. The rapid birth-and-death process underlying the evolution of the large olfactory receptor (OR) gene family has accelerated genomic-level change for the sense of smell in particular. The transition from the land to sea in marine mammals is an attractive model for understanding the influence of habitat shifts on sensory systems, with the retained OR repertoire of baleen whales contrasting with its loss in toothed whales. In this study, we examine to what extent the transition from a terrestrial to a marine environment has influenced the evolution of baleen whale OR repertoires. We developed Gene Mining Pipeline (GMPipe) (https://github.com/AprilJauhal/GMPipe), which can accurately identify large numbers of candidate OR genes. GMPipe identified 707 OR sequences from eight baleen whale species. These repertoires exhibited distinct family count distributions compared to terrestrial mammals, including signs of relative expansion in families OR10, OR11 and OR13. While many receptors have been lost or show signs of random drift in baleen whales, others exhibit signs of evolving under purifying or positive selection. Over 85% of OR genes could be sorted into orthologous groups of sequences containing at least four homologous sequences. Many of these groups, particularly from family OR10, presented signs of relative expansion and purifying selective pressure. Overall, our results suggest that the relatively small size of baleen whale OR repertoires result from specialisation to novel olfactory landscapes, as opposed to random drift.

The sensory system is a target for pharmaceutical therapy of overactive bladder

The concept that “the bladder is an unreliable witness” highlights the non-disease-specific nature of lower urinary tract symptoms (LUTS), which can arise regardless of anatomical differences between genders. This non-specificity has led to the broader classification of symptoms under LUTS, which include storage, voiding, and post-micturition symptoms. Overactive bladder (OAB) is characterised by urgency, often accompanied by frequency, nocturia, and, in some cases, incontinence. The symptoms of OAB do not always correlate with urodynamically proven idiopathic detrusor overactivity (IDO), indicating that afferent nerve activity plays a significant role. The complexity of bladder control involves a neural network spanning the brain, spinal cord, and peripheral ganglia. Current therapies, such as anticholinergics and beta-3 agonists, target both motor and sensory pathways, with emerging evidence suggesting that sensory modulation is crucial for effective treatment. Research using animal models has provided insights into the pharmacological mechanisms underlying bladder function, although these models have limitations in replicating human conditions. The importance of the sensory ‘web’ within the bladder’s mucosal and interstitial cell network is emphasised, as it significantly influences bladder compliance and sensory signalling. Recent advances, including the use of Onabotulinum toxin A and sacral neuromodulation, highlight the therapeutic potential of targeting sensory pathways in managing OAB symptoms.

Skin-inspired multimodal tactile sensor aiming at smart space extravehicular multi-finger operations

Tactile sensing of skin shapes the interactions between hand and the surrounding world, owing to the remarkable natural sensory system. But for astronauts, tactile feedback cannot be obtained biologically due to the very thick protective gloves, which seriously hinders the flexibility of the extravehicular activity. In this work, inspired by human skin, we develop a biomimetic multi-layer tactile sensor (BMLTS) that can work like the fast adaptive and slow adaptive receptors of fingertip to achieve the multimodal tactile perception based on the fusion of thermosensitive, piezoelectric, triboelectric and piezoresistive materials. Based on the BMLTS, the tactile perception for temperature, surface roughness discrimination and smart object grasping is successfully achieved, which fully simulates the basic tactile perceptions in typical extravehicular operations. Furthermore, by the combination of BMLTS and deep learning, a biomimetic intelligent perception system (BIPS) that can make decisions to the tactile signal just like human brain is constructed, which can provide real-time tactile information for astronauts. Intelligent real-time object material identification, writing and recording are conducted using BIPS, reaching the recognition accuracy rate higher than 95%. This work lays the foundation for the systematization and integration of tactile sensors, and paves the way for the development of dexterous tactile perception for smart extravehicular activities of astronauts.

Variable Craniofacial Shape and Development among Multiple Cave-Adapted Populations of Astyanax mexicanus.

Astyanax mexicanus is a freshwater fish species with blind cave morphs and sighted surface morphs. Like other troglodytic species, independently evolved cave-dwelling A. mexicanus populations share several stereotypic phenotypes, including the expansion of certain sensory systems, as well as the loss of eyes and pigmentation. Here, we assess the extent to which there is also parallelism in craniofacial development across cave populations. Since multiple forces may be acting upon variation in the A. mexicanus system, including phylogenetic history, selection, and developmental constraint, several outcomes are possible. For example, eye regression may have triggered a conserved series of compensatory developmental events, in which case we would expect to observe highly similar craniofacial phenotypes across cave populations. Selection for cave-specific foraging may also lead to the evolution of a conserved craniofacial phenotype, especially in regions of the head directly associated with feeding. Alternatively, in the absence of a common axis of selection or strong developmental constraints, craniofacial shape may evolve under neutral processes such as gene flow, drift, and bottlenecking, in which case patterns of variation should reflect the evolutionary history of A. mexicanus. Our results found that cave-adapted populations do share certain anatomical features; however, they generally did not support the hypothesis of a conserved craniofacial phenotype across caves, as nearly every pairwise comparison was statistically significant, with greater effect sizes noted between more distantly related cave populations with little gene flow. A similar pattern was observed for developmental trajectories. We also found that morphological disparity was lower among all three cave populations versus surface fish, suggesting eye loss is not associated with increased variation, which would be consistent with a release of developmental constraint. Instead, this pattern reflects the relatively low genetic diversity within cave populations. Finally, magnitudes of craniofacial integration were found to be similar among all groups, meaning that coordinated development among anatomical units is robust to eye loss in A. mexicanus. We conclude that, in contrast to many conserved phenotypes across cave populations, global craniofacial shape is more variable, and patterns of shape variation are more in line with population structure than developmental architecture or selection.

Combinatorial control of Pseudomonas aeruginosa biofilm development by quorum-sensing and nutrient-sensing regulators.

The human pathogen Pseudomonas aeruginosa, a leading cause of hospital-acquired infections, inhabits and forms sessile antibiotic-resistant communities called biofilms in a wide range of biotic and abiotic environments. In this study, we examined how two global sensory signaling pathways-the RhlR quorum-sensing system and the CbrA/CbrB nutritional adaptation system-intersect to control biofilm development. Previous work has shown that individually these two systems repress biofilm formation. Here, we used biofilm analyses, RNA-seq, and reporter assays to explore the combined effect of information flow through RhlR and CbrA on biofilm development. We find that the ΔrhlRΔcbrA double mutant exhibits a biofilm morphology and an associated transcriptional response distinct from wildtype and the parent ΔrhlR and ΔcbrA mutants indicating codominance of each signaling pathway. The ΔrhlRΔcbrA mutant gains suppressor mutations that allow biofilm expansion; these mutations map to the crc gene resulting in loss of function of the carbon catabolite repression protein Crc. Furthermore, the combined absence of RhlR and CbrA leads to a drastic reduction in the abundance of the Crc antagonist small RNA CrcZ. Thus, CrcZ acts as the molecular convergence point for quorum- and nutrient-sensing cues. We find that in the absence of antagonism by CrcZ, Crc promotes the expression of biofilm matrix components-Pel exopolysaccharide, and CupB and CupC fimbriae. Therefore, this study uncovers a regulatory link between nutritional adaption and quorum sensing with potential implications for anti-biofilm targeting strategies.IMPORTANCEBacteria often form multicellular communities encased in an extracytoplasmic matrix called biofilms. Biofilm development is controlled by various environmental stimuli that are decoded and converted into appropriate cellular responses. To understand how information from two distinct stimuli is integrated, we used biofilm formation in the human pathogen Pseudomonas aeruginosa as a model and studied the intersection of two global sensory signaling pathways-quorum sensing and nutritional adaptation. Global transcriptomics on biofilm cells and reporter assays suggest parallel regulation of biofilms by each pathway that converges on the abundance of a small RNA antagonist of the carbon catabolite repression protein, Crc. We find a new role of Crc as it modulates the expression of biofilm matrix components in response to the environment. These results expand our understanding of the genetic regulatory strategies that allow P. aeruginosa to successfully develop biofilm communities.

Evidence for adaptation of colourful truffle-like fungi for birds in Aotearoa-New Zealand

Propagule dispersal is a crucial aspect of the survival and reproduction of sessile organisms, such as plants and fungi. As such, the colours of fleshy fruits serve as a visual cue for animal dispersers. However, little is known about how, or whether, specific traits of fungal fruiting bodies, such as colour or shape, attract animal dispersers, and additionally the identities of fungal dispersers are poorly understood. Globally, most truffle-like fungi are dull-coloured, subterranean, and likely have scents that are attractive to mammalian dispersers. In Aotearoa-New Zealand, however, brightly coloured truffle-like fungi that emerge from the forest floor have seemingly proliferated. This proliferation has prompted the hypothesis that they are adapted to dispersal by a bird-dominated fauna. In our study, we used the literature and citizen science data (GBIF) to explore whether colourful species occur at a higher proportion of the total truffle-like fungi flora in Aotearoa-New Zealand than elsewhere in the world. In addition, we tested for a relationship between biotic factors (avian frugivory and forest cover) and abiotic factors (precipitation, radiation, and temperature) and the prevalence of brightly coloured truffle-like fungi across the world. The most colourful truffle-like fungi are in three defined regions: Australia, South and Central America and the Caribbean, and Aotearoa-NZ. Potential dispersers and the environment both relate to the distribution of truffle-like fungi: we found that increasing levels of frugivory were associated with higher proportions of colourful truffle-like fungi. This finding provides new insights into drivers of certain fungal traits, and their interactions between birds and fungi. Unique ecosystems, such as Aotearoa-NZ’s bird-dominated biota, provide fascinating opportunities to explore how plants and fungi interact with the sensory systems of animals.

A Polymer Thick Film on an Organic Substrate Grid Electrode and an Open-Source Recording System for UHF MRI: An Imaging Study.

Electrocorticography (ECoG) is a critical tool in preclinical neuroscience research for studying global network activity. However, integrating ECoG with functional magnetic resonance imaging (fMRI) has posed challenges, due to metal electrode interference with imaging quality and heating around the metallic electrodes. Here, we introduce recent advancements in ECoG grid development that utilize a polymer-thick film on an organic substrate (PTFOS). PTFOS offers notable advantages over traditional ECoG grids. Firstly, it significantly reduces imaging artifacts, ensuring minimal interference with MR image quality when overlaying brain tissue with PTFOS grids. Secondly, during a 30-min fMRI acquisition, the temperature increase associated with PTFOS grids is remarkably low, measuring only 0.4 °C. These findings suggest that utilizing ECoG with PTFOS grids has the potential to enhance the safety and efficacy of neurosurgical procedures. By providing clearer imaging results and mitigating risk factors such as excessive heating during MRI scans, PTFOS-based ECoG grids represent a promising advancement in neurosurgical technology. Furthermore, we describe a cutting-edge open-source system designed for simultaneous electrophysiology and fMRI. This system stands out due to its exceptionally low input noise levels (<0.6 V peak-to-peak), robust electromagnetic compatibility (it is suitable for use in MRI environments up to 9.4 teslas), and the inclusion of user-programmable real-time signal-processing capabilities. The open-platform software is a key feature, enabling researchers to swiftly implement and customize real-time signal-processing algorithms to meet specific experimental needs. This innovative system has been successfully utilized in several rodent EEG/fMRI studies, particularly at magnetic field strengths of 4.7 and 9.4 teslas, focusing on the somatosensory system. These studies have allowed for detailed observation of neural activity and responses within this sensory system, providing insights that are critical for advancing our understanding of neurophysiological processes. The versatility and high performance of our system make it an invaluable tool for researchers aiming to integrate and analyze complex datasets from advanced imaging and electrophysiological recordings, ultimately enhancing the depth and scope of neuroscience research.

Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish

In a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.

Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish.

In a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.

(Invited) Towards High-Performance Domain-Specific in-Sensor and in-Memory Accelerators

Internet of Things (IoT) devices are projected to attain an $1100B market by 2025, with a web of interconnection projected to comprise approximately 75+ billion IoT devices. The large number of IoTs consist of sensory systems that enable massive data collection from the environment and people. However, considerable portions of the captured sensory data are redundant and unstructured. Data conversion of such large raw data, storing in volatile memories, transmission, and computation in on-/off-chip processors, impose high energy consumption, latency, and a memory bottleneck at the edge. Therefore, high-speed, low-power, and normally-off computing domain-specific architectures should be explored and developed to overcome these issues. Motivated by the aforementioned concerns, we will be focusing on cross-layer (device/circuit/architecture/application) co-design of energy-efficient and high-performance processing-in-sensor and processing-in-memory platforms for implementing complex AI and machine learning tasks, bioinformatics tasks, graph processing, etc. We explain how to leverage innovations from circuits and architecture to integrate sensors, memory, and logic to break the existing memory and power walls.

Selective injury of thalamocortical tract in neonatal rats impairs forelimb use: model validation and behavioral effects.

Unilateral brain injury in neonates results in largely contralateral hand function in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. To validate that the sensory tract injury impairs dexterity, we modeled the most common site of sensory tract injury in neonates by targeting the thalamocortical tract. In the postnatal day 7 rats, we used three types of lesions to the thalamocortical tract: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the thalamocortical tract, while sparing the adjacent corticospinal tract in the internal capsule. To measure the impact on dexterity, the cylinder exploration and pasta handling tests were used to test the changes of forelimb use at 8 weeks after injury when the rats reached maturity. Lesions to the thalamocortical tract were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury. Overall, specific sensory system lesions of the thalamocortical tract impair forelimb use, suggesting a key role for skilled movement.

Draft Genome of Akame (Lates Japonicus) Reveals Possible Genetic Mechanisms for Long-Term Persistence and Adaptive Evolution with Low Genetic Diversity.

It is known that some endangered species have persisted for thousands of years despite their very small effective population sizes and low levels of genetic polymorphisms. To understand the genetic mechanisms of long-term persistence in threatened species, we determined the whole genome sequences of akame (Lates japonicus), which has survived for a long time with extremely low genetic variations. Genome-wide heterozygosity in akame was estimated to be 3.3 to 3.4 × 10-4/bp, one of the smallest values in teleost fishes. Analysis of demographic history revealed that the effective population size in akame was around 1,000 from 30,000 years ago to the recent past. The relatively high ratio of nonsynonymous to synonymous heterozygosity in akame indicated an increased genetic load. However, a detailed analysis of genetic diversity in the akame genome revealed that multiple genomic regions, including genes involved in immunity, synaptic development, and olfactory sensory systems, have retained relatively high nucleotide polymorphisms. This implies that the akame genome has preserved the functional genetic variations by balancing selection, to avoid a reduction in viability and loss of adaptive potential. Analysis of synonymous and nonsynonymous nucleotide substitution rates has detected signs of positive selection in many akame genes, suggesting adaptive evolution to temperate waters after the speciation of akame and its close relative, barramundi (Lates calcarifer). Our results indicate that the functional genetic diversity likely contributed to the long-term persistence of this species by avoiding the harmful effects of the population size reduction.

Embedded Hybrid-Dimensional Heterointerface for Filament Modulation in 2D Material-Based Artificial Nociceptor.

Nociceptors are key sensory receptors that transmit warning signals to the central nervous system in response to painful stimuli. This fundamental process is emulated in an electronic device by developing a novel artificial nociceptor with an ultrathin, nonstoichiometric gallium oxide (GaOx)-silicon oxide heterostructure. A large-area 2D-GaOx film is printed on a substrate through liquid metal printing to facilitate the production of conductive filaments. This nociceptive structure exhibits a unique short-term temporal response following stimulation, enabling a facile demonstration of threshold-switching physics. The developed heterointerface 2D-GaOx film enables the fabrication of fast-switching, low-energy, and compliance-free 2D-GaOx nociceptors, as confirmed through experiments. The accumulation and extrusion of Ag in the oxide matrix are significant for inducing plastic changes in artificial biological sensors. High-resolution transmission electron microscopy and electron energy loss spectroscopy demonstrate that Ag clusters in the material dispersed under electrical bias and regrouped spontaneously when the bias is removed owing to interfacial energy minimization. Moreover, 2D nociceptors are stable; thus, heterointerface engineering can enable effective control of charge transfer in 2D heterostructural devices. Furthermore, the diffusive 2D-GaOx device and its Ag dynamics enable the direct emulation of biological nociceptors, marking an advancement in the hardware implementation of artificial human sensory systems.

Multimodal In‐Sensor Computing Implemented by Easily‐Fabricated Oxide‐Heterojunction Optoelectronic Synapses

AbstractThe advent of big data and the Internet of Things has created urgent demands for in‐sensor computing hardware with multimodal perception that can effectively resolve the inefficiency, high latency, and excessive energy consumption challenges faced by conventional sensory systems. Here, a simple‐structured optoelectronic synaptic device of In2O3·SnO2/Nb:SrTiO3 (ITO/NSTO) heterostructure is proposed, which vividly demonstrates in‐sensor computing and multimodal perception capabilities. First, with the ingenious synaptic responses of the device under both optical and electrical stimuli, a multimodal in‐sensor neuromorphic computing system capable of concurrently perceiving and processing visual and auditory information is constructed. Using this multimodal system to perform a human emotion recognition task, the misjudgment arising from single‐modal cognition can thereby be effectively avoided. Second, utilizing the integrated sensing and processing functions, along with the dynamic memories of the device array, a neuromorphic vision system is implemented for real‐time monitoring of moving vehicles, which displays high recognition efficiency and accuracy. This research not only provides an optoelectronic synaptic device that is low‐cost and easy to mass‐produce, but also paves the way for next‐generation in‐sensor computing that can efficiently process multimodal signals.

Convergent direct and indirect cortical streams shape avoidance decisions in mice via the midline thalamus

Current concepts of corticothalamic organization in the mammalian brain are mainly based on sensory systems, with less focus on circuits for higher-order cognitive functions. In sensory systems, first-order thalamic relays are driven by subcortical inputs and modulated by cortical feedback, while higher-order relays receive strong excitatory cortical inputs. The applicability of these principles beyond sensory systems is uncertain. We investigated mouse prefronto-thalamic projections to the midline thalamus, revealing distinct top-down control. Unlike sensory systems, this pathway relies on indirect modulation via the thalamic reticular nucleus (TRN). Specifically, the prelimbic area, which influences emotional and motivated behaviors, impacts instrumental avoidance responses through direct and indirect projections to the paraventricular thalamus. Both pathways promote defensive states, but the indirect pathway via the TRN is essential for organizing avoidance decisions through disinhibition. Our findings highlight intra-thalamic circuit dynamics that integrate cortical cognitive signals and their role in shaping complex behaviors.

In-Sensor Organic Electrochemical Transistor for the Multimode Neuromorphic Olfactory System.

The olfactory system is one of the six basic sensory nervous systems. Developing artificial olfactory systems is challenging due to the complexity of chemical information decoding and memory. Conventional chemical sensors can convert chemical signals into electric signals to decode gas information but they lack memory functions. Additional storage and processing units would significantly increase the complexity and power consumption of the devices, especially for portable and wearable devices. Here, an olfactory-inspired in-sensor organic electrochemical transistor (OI-OECT) is proposed, with the integrated functions of chemical information decoding, tunable memory level, and selectivity of vapor sensing. The ion-gel electrolyte endows the OI-OECT with the function of tunable memory levels and a low operating voltage. Typical synaptic behaviors, including inhibitory postsynaptic current and paired-pulse facilitations, are successfully achieved. Importantly, the gas memory level can be effectively modulated by the gate voltages (0 and -1 V), which realized the transformation of volatile and nonvolatile memory. Furthermore, benefiting from the recognition of multiple gases and ability to detect cumulative damage caused by gases, the OI-OECT is demonstrated for early warning system targeting leakage detection of two gases (NH3 and H2S). This work achieves the integrated functions of chemical gas information decode, tunable gas memory level, and selectivity of gas in a single device, which provides a promising pathway for the development of future artificial olfactory systems.

Sensory Changes Related to Swallowing in Motor Neurone Disease.

Dysphagia is common in motor neurone disease (MND) and associated with negative health and psychosocial outcomes. Although largely considered a motor disease, a growing body of evidence suggests that MND can also affect the sensory system. As intact sensation is vital for safe swallowing, and sensory changes can influence the clinical management of dysphagia in people living with MND, this review evaluated and summarised the current evidence for sensory changes related to swallowing in MND. Of 3,481 articles originally identified, 29 met the inclusion criteria. Of these, 20 studies reported sensory changes, which included laryngeal sensation, taste, gag reflex, cough reflex, tongue sensation, smell, palatal and pharyngeal sensation, silent aspiration, and undefined sensation of the swallowing mechanism. Sensory changes were either described as decreased (n = 16) or heightened (n = 4). In the remaining nine studies, sensory function was reported as unaffected. The presence of changes to sensory function related to swallowing in MND remains inconclusive, although an increasing number of studies report sensory changes in some sensory domains. Future research is needed to evaluate the prevalence of sensory changes in MND and how such changes may influence dysphagia and its management.

Contribution of transient receptor potential vanilloid 1 (TRPV1) channel to cholinergic contraction of rat bladder smooth muscle.

Transient receptor potential vanilloid 1 (TRPV1) is a calcium-permeable ion channel that is gated by the pungent constituent of red chili pepper, capsaicin, and by related chemicals from the group of vanilloids, in addition to noxious heat. It is expressed mostly in sensory neurons to act as a detector of painful stimuli produced by pungent chemicals and high temperatures. Although TRPV1 is also found outside the sensory nervous system, its expression and function in the bladder detrusor smooth muscle (DSM) remain controversial. Here, by using Ca2+ imaging and patch clamp on isolated rat DSM cells, in addition to tensiometry on multicellular DSM strips, we show that TRPV1 is expressed functionally in only a fraction of DSM cells, in which it acts as an endoplasmic reticulum Ca2+-release channel responsible for the capsaicin-activated [Ca2+]i rise. Carbachol-stimulated contractions of multicellular DSM strips contain a TRPV1-dependent component, which is negligible in the circular DSM but reaches ≤50% in the longitudinal DSM. Activation of TRPV1 in rat DSM during muscarinic cholinergic stimulation is ensured by phospholipase A2-catalysed derivation of arachidonic acid and its conversion by lipoxygenases to eicosanoids, which act as endogenous TRPV1 agonists. Immunofluorescence detection of TRPV1 protein in bladder sections and isolated DSM cells confirmed both its preferential expression in the longitudinal DSM sublayer and its targeting to the endoplasmic reticulum. We conclude that TRPV1 is an essential contributor to the cholinergic contraction of bladder longitudinal DSM, which might be important for producing spatial and/or temporal anisotropy of bladder wall deformation in different regions during parasympathetic stimulation. KEY POINTS: The transient receptor potential vanilloid 1 (TRPV1) heat/capsaicin receptor/channel is localized in the endoplasmic reticulum membrane of detrusor smooth muscle (DSM) cells of the rat bladder, operating as a calcium-release channel. Isolated DSM cells are separated into two nearly equal groups, within which the cells either show or do not show TRPV1-dependent [Ca2+]i rise. Carbachol-stimulated, muscarinic ACh receptor-mediated contractions of multicellular DSM strips contain a TRPV1-dependent component. This component is negligible in the circular DSM but reaches ≤50% in longitudinal DSM. Activation of TRPV1 in rat DSM during cholinergic stimulation involves phospholipase A2-catalysed derivation of arachidonic acid and its conversion by lipoxygenases to eicosanoids, which act as endogenous TRPV1 agonists.

Transsynaptic BMP Signaling Regulates Fine-Scale Topography between Adjacent Sensory Neurons.

Sensory axons projecting to the central nervous system are organized into topographic maps that represent the locations of sensory stimuli. In some sensory systems, even adjacent sensory axons are arranged topographically, forming "fine-scale" topographic maps. Although several broad molecular gradients are known to instruct coarse topography, we know little about the molecular signaling that regulates fine-scale topography at the level of two adjacent axons. Here, we provide evidence that transsynaptic bone morphogenetic protein (BMP) signaling mediates local interneuronal communication to regulate fine-scale topography in the nociceptive system of Drosophila larvae. We first show that the topographic separation of the axon terminals of adjacent nociceptors requires their common postsynaptic target, the A08n neurons. This phenotype is recapitulated by knockdown of the BMP ligand, Decapentaplegic (Dpp), in these neurons. In addition, removing the Type 2 BMP receptors or their effector (Mad transcription factor) in single nociceptors impairs the fine-scale topography, suggesting the contribution of BMP signaling originated from A08n. This signaling is likely mediated by phospho-Mad in the presynaptic terminals of nociceptors to ensure local interneuronal communication. Finally, reducing Dpp levels in A08n reduces the nociceptor-A08n synaptic contacts. Our data support that transsynaptic BMP signaling establishes the fine-scale topography by facilitating the formation of topographically correct synapses. Local BMP signaling for synapse formation may be a developmental strategy that independently regulates neighboring axon terminals for fine-scale topography.