C. elegans: a sensible model for sensory biology.

From Sydney Brenner's backyard to hundreds of labs across the globe, inspiring six Nobel Prize winners along the way, Caenorhabditis elegans research has come far in the past half century. The journey is not over. The virtues of C. elegans research are numerous and have been recounted extensively. Here, we focus on the remarkable progress made in sensory neurobiology research in C. elegans. This nematode continues to amaze researchers as we are still adding new discoveries to the already rich repertoire of sensory capabilities of this deceptively simple animal. Worms possess the sense of taste, smell, touch, light, temperature and proprioception, each of which is being studied in genetic, molecular, cellular and systems-level detail. This impressive organism can even detect less commonly recognized sensory cues such as magnetic fields and humidity.

Distinct subpopulations of mechanosensory chordotonal organ neurons elicit grooming of the fruit fly antennae.

Diverse mechanosensory neurons detect different mechanical forces that can impact animal behavior. Yet our understanding of the anatomical and physiological diversity of these neurons and the behaviors that they influence is limited. We previously discovered that grooming of the Drosophila melanogaster antennae is elicited by an antennal mechanosensory chordotonal organ, the Johnston's organ (JO) (Hampel et al., 2015). Here, we describe anatomically and physiologically distinct JO mechanosensory neuron subpopulations that each elicit antennal grooming. We show that the subpopulations project to different, discrete zones in the brain and differ in their responses to mechanical stimulation of the antennae. Although activation of each subpopulation elicits antennal grooming, distinct subpopulations also elicit the additional behaviors of wing flapping or backward locomotion. Our results provide a comprehensive description of the diversity of mechanosensory neurons in the JO, and reveal that distinct JO subpopulations can elicit both common and distinct behavioral responses.

Temperature signaling underlying thermotaxis and cold tolerance in Caenorhabditis elegans.

Caenorhabditis elegans has a simple nervous system of 302 neurons. It however senses environmental cues incredibly precisely and produces various behaviors by processing information in the neural circuit. In addition to classical genetic analysis, fluorescent proteins and calcium indicators enable in vivo monitoring of protein dynamics and neural activity on either fixed or free-moving worms. These analyses have provided the detailed molecular mechanisms of neuronal and systemic signaling that regulate worm responses. Here, we focus on responses of C. elegans against temperature and review key findings that regulate thermotaxis and cold tolerance. Thermotaxis of C. elegans has been studied extensively for almost 50 years, and cold tolerance is a relatively recent concept in C. elegans. Although both thermotaxis and cold tolerance require temperature sensation, the responsible neurons and molecular pathways are different, and C. elegans uses the proper mechanisms depending on its situation. We summarize the molecular mechanisms of the major thermosensory circuit as well as the modulatory strategy through neural and tissue communication that enables fine tuning of thermotaxis and cold tolerance.

Sex and species specific hearing mechanisms in mosquito flagellar ears.

Hearing is essential for the courtship of one of the major carriers of human disease, the mosquito. Males locate females through flight-tone recognition and both sexes engage in mid-air acoustic communications, which can take place within swarms containing thousands of individuals. Despite the importance of hearing for mosquitoes, its mechanisms are still largely unclear. We here report a multilevel analysis of auditory function across three disease-transmitting mosquitoes (Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus). All ears tested display transduction-dependent power gain. Quantitative analyses of mechanotransducer function reveal sex-specific and species-specific variations, including male-specific, highly sensitive transducer populations. Systemic blocks of neurotransmission result in large-amplitude oscillations only in male flagellar receivers, indicating sexually dimorphic auditory gain control mechanisms. Our findings identify modifications of auditory function as a key feature in mosquito evolution. We propose that intra-swarm communication has been a driving force behind the observed sex-specific and species-specific diversity.

Notch and Fgf signaling during electrosensory versus mechanosensory lateral line organ development in a non-teleost ray-finned fish.

The lateral line system is a useful model for studying the embryonic and evolutionary diversification of different organs and cell types. In jawed vertebrates, this ancestrally comprises lines of mechanosensory neuromasts over the head and trunk, flanked on the head by fields of electrosensory ampullary organs, all innervated by lateral line neurons in cranial lateral line ganglia. Both types of sense organs, and their afferent neurons, develop from cranial lateral line placodes. Current research primarily focuses on the posterior lateral line primordium in zebrafish, which migrates as a cell collective along the trunk; epithelial rosettes form in the trailing zone and are deposited as a line of neuromasts, within which hair cells and supporting cells differentiate. However, in at least some other teleosts (e.g. catfishes) and all non-teleosts, lines of cranial neuromasts are formed by placodes that elongate to form a sensory ridge, which subsequently fragments, with neuromasts differentiating in a line along the crest of the ridge. Furthermore, in many non-teleost species, electrosensory ampullary organs develop from the flanks of the sensory ridge. It is unknown to what extent the molecular mechanisms underlying neuromast formation from the zebrafish migrating posterior lateral line primordium are conserved with the as-yet unexplored molecular mechanisms underlying neuromast and ampullary organ formation from elongating lateral line placodes. Here, we report experiments in an electroreceptive non-teleost ray-finned fish, the Mississippi paddlefish Polyodon spathula, that suggest a conserved role for Notch signaling in regulating lateral line organ receptor cell number, but potentially divergent roles for the fibroblast growth factor signaling pathway, both between neuromasts and ampullary organs, and between paddlefish and zebrafish.

Cranial nerves in the Australian lungfish, Neoceratodus forsteri, and in fossil relatives (Osteichthyes: Dipnoi).

Three systems, two sensory and one protective, are present in the skin of the living Australian lungfish, Neoceratodus forsteri, and in fossil lungfish, and the arrangement and innervation of the sense organs is peculiar to lungfish. Peripheral branches of nerves that innervate the sense organs are slender and unprotected, and form before any skeletal structures appear. When the olfactory capsule develops, it traps some of the anterior branches of cranial nerve V, which emerged from the chondrocranium from the lateral sphenotic foramen. Cranial nerve I innervates the olfactory organ enclosed within the olfactory capsule and cranial nerve II innervates the eye. Cranial nerve V innervates the sense organs of the snout and upper lip, and, in conjunction with nerve IX and X, the sense organs of the posterior and lateral head. Cranial nerve VII is primarily a motor nerve, and a single branch innervates sense organs in the mandible. There are no connections between nerves V and VII, although both emerge from the brain close to each other. The third associated system consists of lymphatic vessels covered by an extracellular matrix of collagen, mineralised as tubules in fossils. Innervation of the sensory organs is separate from the lymphatic system and from the tubule system of fossil lungfish.

A Computational Model of a Descending Mechanosensory Pathway Involved in Active Tactile Sensing.

Many animals, including humans, rely on active tactile sensing to explore the environment and negotiate obstacles, especially in the dark. Here, we model a descending neural pathway that mediates short-latency proprioceptive information from a tactile sensor on the head to thoracic neural networks. We studied the nocturnal stick insect Carausius morosus, a model organism for the study of adaptive locomotion, including tactually mediated reaching movements. Like mammals, insects need to move their tactile sensors for probing the environment. Cues about sensor position and motion are therefore crucial for the spatial localization of tactile contacts and the coordination of fast, adaptive motor responses. Our model explains how proprioceptive information about motion and position of the antennae, the main tactile sensors in insects, can be encoded by a single type of mechanosensory afferents. Moreover, it explains how this information is integrated and mediated to thoracic neural networks by a diverse population of descending interneurons (DINs). First, we quantified responses of a DIN population to changes in antennal position, motion and direction of movement. Using principal component (PC) analysis, we find that only two PCs account for a large fraction of the variance in the DIN response properties. We call the two-dimensional space spanned by these PCs 'coding-space' because it captures essential features of the entire DIN population. Second, we model the mechanoreceptive input elements of this descending pathway, a population of proprioceptive mechanosensory hairs monitoring deflection of the antennal joints. Finally, we propose a computational framework that can model the response properties of all important DIN types, using the hair field model as its only input. This DIN model is validated by comparison of tuning characteristics, and by mapping the modelled neurons into the two-dimensional coding-space of the real DIN population. This reveals the versatility of the framework for modelling a complete descending neural pathway.

More a finger than a nose: the trigeminal motor and sensory innervation of the Schnauzenorgan in the elephant-nose fish Gnathonemus petersii.

The weakly electric fish Gnathonemus petersii uses its electric sense to actively probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is rich in electroreceptors. Physical measurements have demonstrated the importance of the position of the Schnauzenorgan in funneling the fish's self-generated electric field. The present study focuses on the trigeminal motor pathway that controls Schnauzenorgan movement and on its trigeminal sensory innervation and central representation. The nerves entering the Schnauzenorgan are very large and contain both motor and sensory trigeminal components as well as an electrosensory pathway. With the use of neurotracer techniques, labeled Schnauzenorgan motoneurons were found throughout the ventral main body of the trigeminal motor nucleus but not among the population of larger motoneurons in its rostrodorsal region. The Schnauzenorgan receives no motor or sensory innervation from the facial nerve. There are many anastomoses between the peripheral electrosensory and trigeminal nerves, but these senses remain separate in the sensory ganglia and in their first central relays. Schnauzenorgan trigeminal primary afferent projections extend throughout the descending trigeminal sensory nuclei, and a few fibers enter the facial lobe. Although no labeled neurons could be identified in the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic, possibly proprioceptive, pathway. In this first step toward understanding multimodal central representation of the Schnauzenorgan, no direct interconnections were found between the trigeminal sensory and electromotor command system, or the electrosensory and trigeminal motor command. The pathways linking perception to action remain to be studied.

A biophysical model of adaptive noise filtering in the shark brain.

Sharks detect their prey using an extremely sensitive electrosensory system that is capable of distinguishing weak external stimuli from a relatively strong background noise generated by the animal itself. Experiments indicate that part of the shark's hindbrain, the dorsal octavolateralis nucleus (DON), is responsible for extracting the external stimulus using an adaptive filter mechanism to suppress signals correlated with the shark's breathing motion. The DON's principal neuron integrates input from afferents as well as many thousands of parallel fibres transmitting, inter alia, breathing-correlated motor command signals. There are a number of models in the literature, studying how this adaptive filtering mechanisms occurs, but most of them are based on a spike-train model approach.This paper presents a biophysically based computational simulation which demonstrates a mechanism for adaptive noise filtering in the DON. A spatial model of the neuron uses the Hodgkin-Huxley equations to simulate the propagation of action potentials along the dendrites. Synaptic inputs are modelled by applied currents at various positions along the dendrites, whose input conductances are varied according to a simple learning rule.Simulation results show that the model is able to demonstrate adaptive filtering in agreement with previous experimental and modelling studies. Furthermore, the spatial nature of the model does not greatly affect its learning properties, and in its present form is effectively equivalent to an isopotential model which does not incorporate a spatial element.

Sensory neuroanatomy of stick insects highlights the evolutionary diversity of the orthopteroid subgenual organ complex.

The subgenual organ is a scolopidial sense organ located in the tibia of many insects. In this study the neuroanatomy of the subgenual organ complex of stick insects is clarified for two species, Carausius morosus and Siyploidea sipylus. Neuronal tracing shows a subgenual organ complex that consists of a subgenual organ and a distal organ. There are no differences in neuroanatomy between the three thoracic leg pairs, and the sensory structures are highly similar in both species. A comparison of the neuroanatomy with other orthopteroid insects highlights two features unique in Phasmatodea. The subgenual organ contains a set of densely arranged sensory neurons in the anterior-ventral part of the organ, and a distal organ with 16-17 scolopidial sensilla in C. morosus and 20-22 scolopidial sensilla in S. sipylus. The somata of sensory neurons in the distal organ are organized in a linear array extending distally into the tibia, with only a few exceptions of closely associated neurons. The stick insect sense organs show a case of an elaborate scolopidial sense organ that evolved in addition to the subgenual organ. The neuroanatomy of stick insects is compared to that studied in other orthopteroid taxa (cockroaches, locusts, crickets, tettigoniids). The comparison of sensory structures indicates that elaborate scolopidial organs have evolved repeatedly among orthopteroids. The distal organ in stick insects has the highest number of sensory neurons known for distal organs so far.

Structure, innervation and response properties of integumentary sensory organs in crocodilians.

Integumentary sensory organs (ISOs) are densely distributed on the jaws of crocodilians and on body scales of members of the families Crocodilidae and Gavialidae. We examined the distribution, anatomy, innervation and response properties of ISOs on the face and body of crocodilians and documented related behaviors for an alligatorid (Alligator mississippiensis) and a crocodylid (Crocodylus niloticus). Each of the ISOs (roughly 4000 in A. mississippiensis and 9000 in C. niloticus) was innervated by networks of afferents supplying multiple different mechanoreceptors. Electrophysiological recordings from the trigeminal ganglion and peripheral nerves were made to isolate single-unit receptive fields and to test possible osmoreceptive and electroreceptive functions. Multiple small (<0.1 mm(2)) receptive fields, often from a single ISO, were recorded from the premaxilla, the rostral dentary, the gingivae and the distal digits. These responded to a median threshold of 0.08 mN. The less densely innervated caudal margins of the jaws had larger receptive fields (>100 mm(2)) and higher thresholds (13.725 mN). Rapidly adapting, slowly adapting type I and slowly adapting type II responses were identified based on neuronal responses. Several rapidly adapting units responded maximally to vibrations at 20-35 Hz, consistent with reports of the ISOs' role in detecting prey-generated water surface ripples. Despite crocodilians' armored bodies, the ISOs imparted a mechanical sensitivity exceeding that of primate fingertips. We conclude that crocodilian ISOs have diverse functions, including detection of water movements, indicating when to bite based on direct contact of pursued prey, and fine tactile discrimination of items held in the jaws.

Serotonin-immunoreactive neurons in scorpion pectine neuropils: similarities to insect and crustacean primary olfactory centres?

The pectines of scorpions are a single pair of mechano- and chemosensory appendages located ventrally behind the most posterior pair of walking legs. They are used for probing the substrate in behaviours such as prey tracking and courtship. The sensory afferents on the pectines supply large segmental neuropils with a conspicuous glomerular structure. The pectine neuropils thus bear similarities to insect and crustacean deutocerebral chemosensory centres associated with the antennae, but they also possess idiosyncratic features. One characteristic property of many insect and decapod crustacean olfactory neuropils is their innervation by single, or very few, large serotonergic (inter-) neurons. This feature, among others, has been proposed to support homology of the olfactory lobes in the two arthropod groups. A possible serotonergic innervation of the scorpion pectine neuropils has not yet been studied, despite its apparent diagnostic and functional importance. We thus examined serotonin-immunoreactivity in the pectine neuropils of Androctonus australis and Pandinus imperator. Both scorpion species yielded similar results. The periphery of the neuropil and the matrix between the glomeruli are supplied by a dense network of serotonin-immunoreactive (5-HT-ir) arborisations and varicosities, while the glomeruli themselves are mostly free of 5-HT-ir fibres. The 5-HT-ir supply of the pectine neuropils has two origins. The first is a pair of neurons on each body side, up to 30 µm in diameter and thus slightly larger than the surrounding somata. These cell bodies are and associated with the neuromeres of the genital and pectine segments. The situation is reminiscent of the 5-HT supply of insect and crustacean olfactory and antennal neuropils. The second 5-HT innervation of the pectine neuropils is from a group of some 10-20 ipsilateral neuronal somata of slightly smaller size (15-20 µm). These are part of a much larger 5-HT-ir group comprising 70-90 somata. The whole group is located more anteriorly than the single soma mentioned above, and associated with the neuromere of the last (4th) walking leg. When compared to data from other arthropods, our findings may suggest that glomerular organisation is an ancestral feature of primary chemosensory centres innervated by arthropod appendages. This idea needs further scrutiny, although supporting evidence may have been overlooked previously, due to the small size of chemosensory neuropils in walking legs and in reduced segmental appendages.

The paratympanic organ: a barometer and altimeter in the middle ear of birds?

A century has passed since the discovery of the paratympanic organ (PTO), a mechanoreceptive sense organ in the middle ear of birds and other tetrapods. This luminal organ contains a sensory epithelium with typical mechanosensory hair cells and may function as a barometer and altimeter. The organ is arguably the most neglected sense organ in living tetrapods. The PTO is believed to be homologous to a lateral line sense organ, the spiracular sense organ of nonteleostean fishes. Our review summarizes the current state of knowledge of the PTO and draws attention to the astounding lack of information about the unique and largely unexplored sensory modality of barometric perception.

Histamine-immunoreactive local neurons in the antennal lobes of the hymenoptera.

Neural networks receive input that is transformed before being sent as output to higher centers of processing. These transformations are often mediated by local interneurons (LNs) that influence output based on activity across the network. In primary olfactory centers, the LNs that mediate these lateral interactions are extremely diverse. For instance, the antennal lobes (ALs) of bumblebees possess both gamma-aminobutyric acid (GABA)- and histamine-immunoreactive (HA-ir) LNs, and both are neurotransmitters associated with fast forms of inhibition. Although the GABAergic network of the AL has been extensively studied, we sought to examine the anatomical features of the HA-ir LNs in relation to the other cellular elements of the bumblebee AL. As a population, HA-ir LNs densely innervate the glomerular core and sparsely arborize in the outer glomerular rind, overlapping with the terminals of olfactory receptor neurons. Individual fills of HA-ir LNs revealed heavy arborization of the outer ring of a single "principal" glomerulus and sparse arborization in the core of other glomeruli. In contrast, projection neurons and GABA-immunoreactive LNs project throughout the glomerular volume. To provide insight into the selective pressures that resulted in the evolution of HA-ir LNs, we determined the phylogenetic distribution of HA-ir LNs in the AL. HA-ir LNs were present in all but the most basal hymenopteran examined, although there were significant morphological differences between major groups within the Hymenoptera. The ALs of other insect taxa examined lacked HA-ir LNs, suggesting that this population of LNs arose within the Hymenoptera and underwent extensive morphological modification.

Visceral organ cross-sensitization - an integrated perspective.

Viscero-somatic referral and sensitization has been well documented clinically and widely investigated, whereas viscero-visceral referral and sensitization (termed cross-organ sensitization) has only recently received attention as important to visceral disease states. Because second order neurons in the CNS have been extensively shown to receive convergent input from different visceral organs, it has been assumed that cross-organ sensitization arises by the same convergence-projection mechanism as advanced for viscero-somatic referral and sensitization. However, increasing evidence also suggests participation of peripheral mechanisms to explain referral and sensitization. We briefly summarize behavioral, morphological and physiological support of and focus on potential mechanisms underlying cross-organ sensitization.

Ultrastructure of the extensively developed nuchal organs of Laonice bahusiensis (Annelida: Canalipalpata: Spionidae).

The nuchal organs of annelid Laonice bahusiensis (Spionidae) from northern Europe have been studied using scanning and transmission electron microscopy. L. bahusiensis is the first spionid species in which extensively developed, continuous nuchal organs are described. The nuchal organs of this genus are the longest known among polychaete annelids. They consist of paired double bands extending from the prostomium on a mid-dorsal caruncle for about 24-30 setigers. Their microanatomy corresponds to the general structural plan of nuchal organs: there are ciliated supporting cells and bipolar sensory cells with sensory cilia traversing an olfactory chamber. The organs are overlaid by a secondary paving-stone-like cover and innervated by one pair of longitudinally elongated nuchal nerves. These findings clearly favor the hypothesis that the paired, extensively developed ciliated structures found in some Spionidae are homologous with the prostomial nuchal organs characteristic of polychaete annelids.

Different growth patterns of two adjacent glomeruli responsible for sex-pheromone processing during postembryonic development of the cockroach Periplaneta americana.

In many insect species, sex pheromone is processed by specific, enlarged glomeruli in the antennal lobes of males. In the male American cockroach, two closely located glomeruli (A and B) are responsible for processing the major pheromone components (periplanone-A and -B, respectively), and these collectively form the macroglomerular complex. Afferents originating from the dorsal and ventral surfaces of the antenna tend to project to the anterior and posterior regions of the macroglomerular complex via the dorsal and ventral antennal nerves, respectively. This topographic segregation of afferents is seen only in the macroglomerular complex, and not in other glomeruli that process normal environmental odors. Using differential, anterograde dye injection into the two antennal sensory nerves, we show that the macroglomerular complex is not formed by fusion of several glomeruli, as suggested in previous studies, but that the precursors of the A- and B-glomeruli already exist in the first larval instar. The volume of afferents in the macroglomerular complex precursor increases nearly exponentially with molting times, 430-fold from the first instar to the adult. The A- and B-glomeruli both undergo continuous growth during postembryonic development, but peak growth rates occur in different larval stages. The growth rate of the B-glomerulus peaked in the mid-developmental stage then declined, while growth of A-glomerulus was maintained at low level in early- to mid-developmental stages but increased greatly in later stages. These results suggest perception of sex pheromone occurs in early instars, and that PA and PB have distinct roles in different developmental stages.

Three-dimensional reconstruction and neural map of the serotonergic brain of Asplanchna brightwellii (Rotifera, Monogononta).

The basic organization of the rotifer brain has been known for nearly a century; yet, fine details on its structure and organization remain limited despite the importance of rotifers in studies of evolution and population biology. To gain insight into the structure of the rotifer brain, and provide a foundation for future neurophysiologic and neurophylogenetic research, the brain of Asplanchna brightwellii was studied with immunohistochemistry, confocal laser scanning microscopy, and computer modeling. A three-dimensional map of serotonergic connections reveals a complex network of approximately 28 mostly unipolar, cerebral perikarya and associated neurites. Cells and their projections display symmetry in quantity, size, connections, and pathways between cerebral hemispheres within and among individuals. Most immunopositive cells are distributed close to the brain midline. Three pairs of neurites form decussations at the brain midline and may innervate sensory receptors in the corona. A single neuronal pathway appears to connect both the lateral horns and dorsolateral apical receptors, suggesting that convergence of synaptic connections may be common in the afferent sensory systems of rotifers. Results show that the neural map of A. brightwellii is much more intricate than that of other monogonont rotifers; nevertheless, the consistency in neural circuits provides opportunities to identify homologous neurons, distinguish functional regions based on neurotransmitter phenotype, and explore new avenues of neurophylogeny in Rotifera.