Types Of Sensory Neurons Research Articles

Defining specificity determinants of cGMP mediated gustatory sensory transduction in Caenorhabditis elegans.

Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode Caenorhabditis elegans was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the gcy genes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the tax-2 and tax-4 genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the che-6 locus. che-6 mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking the tax-2 and tax-4 CNG channels. In contrast, thermosensory signal transduction, which also requires tax-2 and tax-4, does not require che-6, but requires another CNG, cng-3. We propose that CHE-6 may form together with two other CNG subunits, TAX-2 and TAX-4, a gustatory neuron-specific heteromeric CNG channel complex.

Experience-Dependent versus Experience-Independent Postembryonic Development of Distinct Groups of Zebrafish Olfactory Glomeruli

Olfactory glomeruli are innervated with great precision by the axons of different olfactory sensory neuron types and act as functional units in odor information processing. Approximately 140 glomeruli are present in each olfactory bulb of adult zebrafish; these units consist of either highly stereotypic large glomeruli or smaller anatomically indistinguishable glomeruli. In the present study, we investigated developmental differences among these types of glomeruli. We observed that 10 large and individually identifiable glomeruli already developed before hatching, at 72 h after fertilization, in configurations that resembled their mature organization. However, the cross-sectional area of these glomeruli increased throughout larval development, and they eventually comprised the largest units in postlarval olfactory bulbs. In contrast, small and anatomically indistinguishable glomeruli formed only after hatching, apparently by segregating from five larger precursors that were identifiable during embryonic development. The differentiation of these small glomeruli proceeded with conspicuous variation in number and arrangement, both among larvae and between olfactory bulbs of the same individuals. To determine factors that might contribute to this variability, we investigated the effects of olfactory enrichment on the development of amino acid-responsive lateral glomeruli, which include both large and small units. Larvae reared in an amino acid-enriched environment had normal large lateral glomeruli, but the small lateral glomeruli were more numerous and displayed reduced cross-sectional areas compared with glomeruli in control animals. Our results suggest that large and small glomeruli mature via distinct developmental processes that may be differentially influenced by sensory experience.

Modeling of genetic regulatory networks in the differentiation of neural crest stem cells to sensory neurons by means of boolean networks

In the present study we have generated a GRN comprising the process by which neural crest stem cells develop to two types of sensory neurons (Propioceptors and Nocioceptors). We have also been able to find patterns of regulation (motifs) that act cooperatively to control such process. Surprisingly, these motifs take place in similar stages during the development of erythrocytes from hematopoietic stem cells. Regarding the complexity of the GRN found, we then used Random Boolean Networks (RBN) for this purpose, which showed key components as well as the dynamics of the process through changes in initial conditions. Finally, the motifs were reflected in the model, suggesting insights for further studies.

Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation

Touch sensation is essential for behaviours ranging from environmental exploration to social interaction; however, the underlying mechanisms are largely unknown. In Drosophila larvae, two types of sensory neurons, class III and class IV dendritic arborization neurons, tile the body wall. The mechanotransduction channel PIEZO in class IV neurons is essential for sensing noxious mechanical stimuli but is not involved in gentle touch. On the basis of electrophysiological-recording, calcium-imaging and behavioural studies, here we report that class III dendritic arborization neurons are touch sensitive and contribute to gentle-touch sensation. We further identify NOMPC (No mechanoreceptor potential C), a member of the transient receptor potential (TRP) family of ion channels, as a mechanotransduction channel for gentle touch. NOMPC is highly expressed in class III neurons and is required for their mechanotransduction. Moreover, ectopic NOMPC expression confers touch sensitivity to the normally touch-insensitive class IV neurons. In addition to the critical role of NOMPC in eliciting gentle-touch-mediated behavioural responses, expression of this protein in the Drosophila S2 cell line also gives rise to mechanosensitive channels in which ion selectivity can be altered by NOMPC mutation, indicating that NOMPC is a pore-forming subunit of a mechanotransduction channel. Our study establishes NOMPC as a bona fide mechanotransduction channel that satisfies all four criteria proposed for a channel to qualify as a transducer of mechanical stimuli and mediates gentle-touch sensation. Our study also suggests that different mechanosensitive channels may be used to sense gentle touch versus noxious mechanical stimuli.

Organization of antennal lobe‐associated neurons in adult Drosophila melanogaster brain

The primary olfactory centers of both vertebrates and insects are characterized by glomerular structure. Each glomerulus receives sensory input from a specific type of olfactory sensory neurons, creating a topographic map of the odor quality. The primary olfactory center is also innervated by various types of neurons such as local neurons, output projection neurons (PNs), and centrifugal neurons from higher brain regions. Although recent studies have revealed how olfactory sensory input is conveyed to each glomerulus, it still remains unclear how the information is integrated and conveyed to other brain areas. By using the GAL4 enhancer-trap system, we conducted a systematic mapping of the neurons associated with the primary olfactory center of Drosophila, the antennal lobe (AL). We identified in total 29 types of neurons, among which 13 are newly identified in the present study. Analyses of arborizations of these neurons in the AL revealed how glomeruli are linked with each other, how different PNs link these glomeruli with multiple secondary sites, and how these secondary sites are organized by the projections of the AL-associated neurons.

BMP and Delta/Notch signaling control the development of amphioxus epidermal sensory neurons: insights into the evolution of the peripheral sensory system

The evolution of the nervous system has been a topic of great interest. To gain more insight into the evolution of the peripheral sensory system, we used the cephalochordate amphioxus. Amphioxus is a basal chordate that has a dorsal central nervous system (CNS) and a peripheral nervous system (PNS) comprising several types of epidermal sensory neurons (ESNs). Here, we show that a proneural basic helix-loop-helix gene (Ash) is co-expressed with the Delta ligand in ESN progenitor cells. Using pharmacological treatments, we demonstrate that Delta/Notch signaling is likely to be involved in the specification of amphioxus ESNs from their neighboring epidermal cells. We also show that BMP signaling functions upstream of Delta/Notch signaling to induce a ventral neurogenic domain. This patterning mechanism is highly similar to that of the peripheral sensory neurons in the protostome and vertebrate model animals, suggesting that they might share the same ancestry. Interestingly, when BMP signaling is globally elevated in amphioxus embryos, the distribution of ESNs expands to the entire epidermal ectoderm. These results suggest that by manipulating BMP signaling levels, a conserved neurogenesis circuit can be initiated at various locations in the epidermal ectoderm to generate peripheral sensory neurons in amphioxus embryos. We hypothesize that during chordate evolution, PNS progenitors might have been polarized to different positions in various chordate lineages owing to differential regulation of BMP signaling in the ectoderm.

CNG-Modulin: A Novel Ca-Dependent Modulator of Ligand Sensitivity in Cone Photoreceptor cGMP-Gated Ion Channels

The transduction current in several different types of sensory neurons arises from the activity of cyclic nucleotide-gated (CNG) ion channels. The channels in these sensory neurons vary in structure and function, yet each one demonstrates calcium-dependent modulation of ligand sensitivity mediated by the interaction of the channel with a soluble modulator protein. In cone photoreceptors, the molecular identity of the modulator protein was previously unknown. We report the discovery and characterization of CNG-modulin, a novel 301 aa protein that interacts with the N terminus of the β subunit of the cGMP-gated channel and modulates the cGMP sensitivity of the channels in cone photoreceptors of striped bass (Morone saxatilis). Immunohistochemistry and single-cell PCR demonstrate that CNG-modulin is expressed in cone but not rod photoreceptors. Adding purified recombinant CNG-modulin to cone membrane patches containing the native CNG channels shifts the midpoint of cGMP dependence from ∼91 μM in the absence of Ca(2+) to ∼332 μM in the presence of 20 μM Ca(2+). At a fixed cGMP concentration, the midpoint of the Ca(2+) dependence is ∼857 nM Ca(2+). These restored physiological features are statistically indistinguishable from the effects of the endogenous modulator. CNG-modulin binds Ca(2+) with a concentration dependence that matches the calcium dependence of channel modulation. We conclude that CNG-modulin is the authentic Ca(2+)-dependent modulator of cone CNG channel ligand sensitivity. CNG-modulin is expressed in other tissues, such as brain, olfactory epithelium, and the inner ear, and may modulate the function of ion channels in those tissues as well.

The transcription factor Cux2 marks development of an A-delta sublineage of TrkA sensory neurons

The developmental process and unique molecular identity between the many different types of dorsal root ganglion (DRG) sensory neurons generated during embryogenesis provide the cellular basis for the distinct perceptual modalities of somatosensation. The mechanisms leading to the generation of different types of nociceptive sensory neurons remain only partly understood. Here, we show that the transcription factor Cux2 is a novel marker of sensory neuron subpopulations of three main sublineages as defined by the expression of neurotrophic factor receptors TrkA, TrkB and TrkC. In particular, it is expressed in a subpopulation of early TrkA + neurons that arise during the early, Ngn1-independent initiated neurogenesis in the DRG. Postnatally, Cux2 marks a specific subtype of A-delta nociceptors as seen by expression of TrkA and NF200 but absence of TrpV1. Analysis of Cux2 mutant mice shows that Cux2 is not required for specification of Trk + neuronal subpopulations. However, Cux2 mutant mice are hypersensitive to mechanical, but not to heat or cold stimuli, consistent with a requirement in the process of specification of the mechanoreceptive neuron circuit. Hence, our results show that Cux2 is expressed and may participate in development of a specific subtype of myelinated TrkA + nociceptors.

Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of altered semaphorin 6D signaling inhibit synapse formation

Different types of sensory neurons in the dorsal root ganglia project axons to the spinal cord to convey peripheral information to the central nervous system. Whereas most proprioceptive axons enter the spinal cord medially, cutaneous axons typically do so laterally. Because heavily myelinated proprioceptive axons project to the ventral spinal cord, proprioceptive axons and their associated oligodendrocytes avoid the superficial dorsal horn. However, it remains unclear whether their exclusion from the superficial dorsal horn is an important aspect of neural circuitry. Here we show that a mouse null mutation of Sema6d results in ectopic placement of the shafts of proprioceptive axons and their associated oligodendrocytes in the superficial dorsal horn, disrupting its synaptic organization. Anatomical and electrophysiological analyses show that proper axon positioning does not seem to be required for sensory afferent connectivity with motor neurons. Furthermore, ablation of oligodendrocytes from Sema6d mutants reveals that ectopic oligodendrocytes, but not proprioceptive axons, inhibit synapse formation in Sema6d mutants. Our findings provide new insights into the relationship between oligodendrocytes and synapse formation in vivo, which might be an important element in controlling the development of neural wiring in the central nervous system.

Corneal Sensitivity in Diabetic Patients Subjected to Retinal Laser Photocoagulation

To determine the changes in corneal sensitivity to different stimulus modalities in diabetes mellitus (DM)1 and DM2 patients with retinopathy, and to explore whether argon laser photocoagulation exacerbates sensitivity loss in diabetic patients. Corneal sensitivity to different modalities of stimulus was determined in one randomized eye in 52 patients with DM1 (n = 35) or DM2 (n = 17), and in 27 healthy subjects. Medical history was obtained from all the patients, including age, sex, time from DM diagnosis, type of diabetes, time from onset of retinopathy, type of diabetic retinopathy, and type of argon laser treatment. Corneal sensitivity was determined using a gas esthesiometer. Mechanical, chemical, and thermal (heat and cold) stimuli were applied on the central cornea. Sensitivity thresholds to selective mechanical, chemical, and cold stimulation were significantly higher in DM patients compared to controls. Sensitivity threshold to mechanical and chemical stimuli was higher in DM2 than in DM1 patients. In DM1 patients, mechanical threshold increased with time after DM diagnosis. No correlation was found between sensitivity thresholds to chemical or thermal stimulation and the age of the patient, type of retinopathy, or time from its diagnosis. Laser treatment generated a further impairment of corneal sensitivity. Corneal sensitivity to mechanical, chemical, and thermal stimulation is decreased in DM patients, suggesting that diabetes affects homogeneously the different types of sensory neurons innervating the cornea. Corneal sensitivity appears to be more disturbed in DM2 than in DM1. Laser treatment of DM patients generates a further impairment in corneal sensitivity, probably as the result of physical damage to ciliary nerves.

Transcription Factor Short Stature Homeobox 2 Is Required for Proper Development of Tropomyosin-Related Kinase B-Expressing Mechanosensory Neurons

Dorsal root ganglia (DRG) contain somatosensory neurons of diverse sensory modalities. Among these different types of sensory neurons, the molecular mechanisms that regulate the development and specification of touch neurons are the least well understood. We took a candidate approach and searched for transcription factors that are expressed in subsets of DRG neurons, and found that the transcription factor Shox2 (short stature homeobox 2) is expressed in subpopulations of TrkB (tropomyosin-related kinase B)- and Ret-expressing neurons at neonatal stages. Since TrkB is a known marker that is selectively expressed in touch sensory neurons, we decided to examine the function of Shox2 in specifying TrkB-positive DRG neurons. Conditional deletion of Shox2 in neural crest cells (which give rise to all DRG neurons) caused a 60 ∼ 65% reduction in the number of TrkB-expressing neurons. It also resulted in an increase in coexpression of TrkC in Ret-positive sensory neurons. Deletion of Shox2 in differentiating DRG neurons at later time points caused only a moderate reduction in TrkB expression. Overexpression of Shox2 in all neural crest cells resulted in a small increase in the number of TrkB-expressing neurons. Finally, Shox2 deletion also caused reduced touch sensory axonal innervation to layers III/IV of the spinal cord. Together, our findings identify Shox2 as an essential but not sufficient component of the transcription programs required in neural progenitor cells for the proper specification of subsets of TrkB-expressing touch/mechanosensory neurons.

Regulation of Response Properties and Operating Range of the AFD Thermosensory Neurons by cGMP Signaling

The neuronal mechanisms that encode specific stimulus features in order to elicit defined behavioral responses are poorly understood. C. elegans forms a memory of its cultivation temperature (T(c)) and exhibits distinct behaviors in different temperature ranges relative to T(c). In particular, C. elegans tracks isotherms only in a narrow temperature band near T(c). T(c) memory is in part encoded by the threshold of responsiveness (T∗(AFD)) of the AFD thermosensory neuron pair to temperature stimuli. However, because AFD thermosensory responses appear to be similar at all examined temperatures above T∗(AFD), the mechanisms that generate specific behaviors in defined temperature ranges remain to be determined. Here, we show that the AFD neurons respond to the sinusoidal variations in thermal stimuli followed by animals during isothermal tracking (IT) behavior only in a narrow temperature range near T(c). We find that mutations in the AFD-expressed gcy-8 receptor guanylyl cyclase (rGC) gene result in defects in the execution of IT behavior and are associated with defects in the responses of the AFD neurons to oscillating thermal stimuli. In contrast, mutations in the gcy-18 or gcy-23 rGCs alter the temperature range in which IT behavior is exhibited. Alteration of intracellular cGMP levels via rGC mutations or addition of cGMP analogs shift the lower and upper ranges of the temperature range of IT behavior in part via alteration in T∗(AFD). Our observations provide insights into the mechanisms by which a single sensory neuron type encodes features of a given stimulus to generate different behaviors in defined zones.

H3 Receptors and Pain Modulation: Peripheral, Spinal, and Brain Interactions

Histamine H(3) receptors (H(3)Rs), distributed within the brain, the spinal cord, and on specific types of primary sensory neurons, can modulate pain transmission by several mechanisms. In the skin, H(3)Rs are found on certain Aβ fibers, and on keratinocytes and Merkel cells, as well as on deep dermal, peptidergic Aδ fibers terminating on deep dermal blood vessels. Activation of H(3)Rs on the latter in the skin, heart, lung, and dura mater reduces calcitonin gene-related peptide and substance P release, leading to anti-inflammatory (but not antinociceptive) actions. However, activation of H(3)Rs on the spinal terminals of these sensory fibers reduces nociceptive responding to low-intensity mechanical stimuli and inflammatory stimuli such as formalin. These findings suggest that H(3)R agonists might be useful analgesics, but these drugs have not been tested in clinically relevant pain models. Paradoxically, H(3) antagonists/inverse agonists have also been reported to attenuate several types of pain responses, including phase II responses to formalin. In the periaqueductal gray (an important pain regulatory center), the H(3) inverse agonist thioperamide releases neuronal histamine and mimics histamine's biphasic modulatory effects in thermal nociceptive tests. Newer H(3) inverse agonists with potent, selective, and brain-penetrating properties show efficacy in several neuropathic and arthritis pain models, but the sites and mechanisms for these actions remain poorly understood.

Complete mapping of glomeruli based on sensory nerve branching pattern in the primary olfactory center of the cockroach Periplaneta americana

AbstractGlomeruli are structural and functional units in the primary olfactory center in vertebrates and insects. In the cockroach Periplaneta americana, axons of different types of sensory neurons housed in sensilla on antennae form dorsal and ventral antennal nerves and then project to a number of glomeruli. In this study, we identified all antennal lobe (AL) glomeruli based on detailed innervation patterns of sensory tracts in addition to the shape, size, and locations in the cockroach. The number of glomeruli is ∼205, and no sex‐specific difference is observed. Anterograde dye injections into the antennal nerves revealed that axons supplying the AL are divided into 10 sensory tracts (T1–T10). Each of T1–T3 innervates small, oval glomeruli in the anteroventral region of the AL, with sensory afferents invading each glomerulus from multiple directions, whereas each of T4–T10 innervates large glomeruli with various shapes in the posterodorsal region, with a bundle of sensory afferents invading each glomerulus from one direction. The topographic branching patterns of all these tracts are conserved among individuals. Sensory afferents in a sub‐tract of T10 had axon terminals in the dorsal margin of the AL and the protocerebrum, where they form numerous small glomerular structures. Sensory nerve branching pattern should reflect developmental processes to determine spatial arrangement of glomeruli, and thus the complete map of glomeruli based on sensory nerve branching pattern should provide a basis for studying the functional significance of spatial arrangement of glomeruli and its developmental basis. J. Comp. Neurol. 518:3907–3930, 2010. © 2010 Wiley‐Liss, Inc.

Complete mapping of glomeruli based on sensory nerve branching pattern in the primary olfactory center of the cockroach Periplaneta americana

Glomeruli are structural and functional units in the primary olfactory center in vertebrates and insects. In the cockroach Periplaneta americana, axons of different types of sensory neurons housed in sensilla on antennae form dorsal and ventral antennal nerves and then project to a number of glomeruli. In this study, we identified all antennal lobe (AL) glomeruli based on detailed innervation patterns of sensory tracts in addition to the shape, size, and locations in the cockroach. The number of glomeruli is approximately 205, and no sex-specific difference is observed. Anterograde dye injections into the antennal nerves revealed that axons supplying the AL are divided into 10 sensory tracts (T1-T10). Each of T1-T3 innervates small, oval glomeruli in the anteroventral region of the AL, with sensory afferents invading each glomerulus from multiple directions, whereas each of T4-T10 innervates large glomeruli with various shapes in the posterodorsal region, with a bundle of sensory afferents invading each glomerulus from one direction. The topographic branching patterns of all these tracts are conserved among individuals. Sensory afferents in a sub-tract of T10 had axon terminals in the dorsal margin of the AL and the protocerebrum, where they form numerous small glomerular structures. Sensory nerve branching pattern should reflect developmental processes to determine spatial arrangement of glomeruli, and thus the complete map of glomeruli based on sensory nerve branching pattern should provide a basis for studying the functional significance of spatial arrangement of glomeruli and its developmental basis.

Evolution of bistable dynamics in spiking neural controllers for agents performing olfactory attraction and aversion

Research on the olfactory system of Drosophila has shown that individual glomeruli mediate innate olfactory attraction and aversion [1]. The authors showed that increasing concentrations of vinegar result in excitation of an additional glomerulus, which can initiate a behavioral switch from attraction to aversion. This implies that high concentrations of vinegar activate a specific set of sensory neurons that is not activated by low concentrations. In this research, we used a genetic algorithm to evolve spiking neural controllers for agents that were attracted by low concentrations of a simulated chemical but were repelled by high concentrations of the same chemical. We investigated how the evolved neural controllers could encode information about the chemical concentration to perform this task. We also wanted to see if the neural controllers needed to be equipped with different types of olfactory sensory neurons or if only one type was sufficient. We first performed experiments where the agent could use only one kind of sensors that responded to the whole range of concentrations. In a second set of experiments, the agents could use an additional pair of sensors only activated by high concentrations. In our model, simulated agents could move in a 2D environment and the neural controller was placed on a 2D substrate. We used leaky integrate-and-fire neurons with temporal synaptic integration and transmission delays. The neural network was generated using a developmental model with an indirect encoding strategy that mapped an artificial genome onto the network connectivity. Our model was able to evolve neural controllers with complex dynamics that used both neuronal firing rates and temporal coincidence to encode information about the olfactory environment. Surprisingly, the fittest evolved agent did not require an additional pair of sensors that responded only to high concentrations, different from what has been observed in Drosophila. A central feature that implemented the attraction and aversion behavior of the agent was the combination of bilateral inhibition and excitatory self-connections. This resulted in a cascade of two bi-stable systems, one of which was responsible for basic motor control and for attraction at low concentrations. The second bi-stable system controlled the switching between the states of the first bi-stable system when the concentration was too high. These results show that an artificial life based approach to the study of natural processes like olfaction is feasible, and that it can suggest neural coding strategies that may be used by natural systems.

Kinetic properties of mechanically activated currents in spinal sensory neurons

Dorsal root ganglion neurons in vitro express a number of types of mechanically activated currents that are thought to underlie somatic mechanosensory transduction in vivo. We have studied the inactivation properties of these currents to assess how they might influence the electrophysiological responses of dorsal root ganglion (DRG) neurons to mechanical stimulation. We show that the speed of ramp-like mechanical stimulation determines the dynamics of mechanically activated current responses and hence the type of DRG neuron most likely to be activated. We also show that both rapidly and slowly adapting currents inactivate as a function of membrane stretch. However, the rapidly adapting current inactivation time course is mainly dependent on channel opening whilst slowly adapting current kinetics are dependent on membrane stretch. In response to repeated stimulation, slowly adapting currents inactivate less and recover more quickly than rapidly adapting currents. Therefore, vibratory stimuli tend to inactivate rapidly adapting currents whilst static stimuli tend to inactivate slowly adapting currents. Current clamp experiments show that, physiologically, the response of different types of sensory neurons is dictated primarily by the static or dynamic nature of the mechanical stimulus and the interplay between voltage-gated and mechanically gated ion channels expressed in these neurons.

Conditioning lesions enhance growth state only in sensory neurons lacking calcitonin gene-related peptide and isolectin B4-binding

A conditioning lesion improves regeneration of central and peripheral axons of dorsal root ganglion (DRG) neurons after a subsequent injury by enhancing intrinsic growth capacity. This enhanced growth state is also observed in cultured DRG neurons, which support a more sparsely and rapidly elongating mode of growth after a prior conditioning lesion in vivo. Here we examined differences in the capacity or requirements of specific types of sensory neurons for regenerative growth, which has important consequences for development of strategies to improve recovery after injury. We showed that after partial or complete injury of the sciatic nerve in mice, an elongating mode of growth in vitro was activated only in DRG neurons that did not express calcitonin gene-related peptide (CGRP) or bind Bandeiraea simplicifolia I-isolectin B4 (IB4). We also directly examined the response of conditioned sensory neurons to nerve growth factor (NGF), which does not enhance growth in injured peripheral nerves in vivo. We showed that after partial injury, NGF stimulated a highly branched and linearly restricted rather than elongating mode of growth. After complete injury, the function of NGF was impaired, which immunohistochemical studies of DRG indicated was at least partly due to downregulation of the NGF receptor, tropomyosin-related kinase A (TrkA). These results suggest that, regardless of the type of conditioning lesion, each type of DRG neuron has a distinct intrinsic capacity or requirement for the activation of rapidly elongating growth, which does not appear to be influenced by NGF.

Structure–function relationship of sensory endings in the gut and bladder

Visceral afferents play a key role in neural circuits underlying the physiological function of visceral organs. They are responsible for the detection and transmission of a variety of visceral sensations (e.g. satiety, urge, discomfort and pain) from the viscera to the central nervous system. A comprehensive account of the different functional types of visceral sensory neurons would be invaluable in understanding how sensory dysfunction occurs and how it might be diagnosed and treated. Our aim was to explore the morphology of different nerve endings of visceral afferents within the gastrointestinal tract and urinary bladder and how the morphology of these nerve endings may relate to their functional properties. Morphological studies of mechanosensitive endings of visceral afferents to the gut and bladder correlated with physiological recordings have added a new dimension to our ability to distinguish different functional classes of visceral afferents.

Expression of odorant receptor genes on the olfactory epithelium following olfactory nerve disconnection

To constitute the animal model of unilateral olfactory nerve transection and observe the expression level and distribution of odorant receptors. Thirty-two rats were divided into two groups: the olfactory nerve transection group (20) and the control group (12). The former group received the operation to transect the left olfactory nerve following the left olfactory bulb was exposed under microscope and the latter group did not give any disposal. At every stage of five days, two weeks, four weeks and six weeks after the operation, five rats from the nerve transection group and three from the control group were anaesthetized simultaneously, and olfactory epithelium were taken out after transcardial perfusion, then paraffin imbedding. Coronal sections were sliced for HE staining to observe the thickness changes of the olfactory epithelium, and for in situ hybridization (ISHs) to investigate the expression of olfactory receptor genes (Olr287, Olr226, Olr1493 and Olr1654) in the epithelium, also to evaluate the changes of the expression level and location of the selected receptors during the regeneration of olfactory epithelium. HE staining showed that 5 days after the operation cell quantity and thickness of the olfactory epithelium decreased obviously, which increased gradually 2 or 4 weeks after operation. After 6 weeks' recovery, the thickness of the epithelium could reach the control level. The pattern of cell staining by ISH showed a specific spatial distribution along the anteroposterior (AP) and dorsoventral (DV) axis. Evidence suggested that odorant receptors were distributed in continuous and multiple overlapping bands in the normal or nerve transected-recovered epithelium rather than in the conventionally accepted three or four zones. The data also demonstrated that the distribution of sensory neuron types, as identified and defined by odorant receptor expression, was restored to normal or nearly so by 6 weeks after operation. Likewise, the numbers of probe-labeled neurons in the nerve transected-recovered had an obvious decrease 5 days after olfactory nerve transection. Reactive cells (x(-) +/- s) of Olr1493 in the operated side was (53.9 +/- 19.9), compared with (419.0 +/- 21.2) in the unoperated side, there was statistic significance between them (t = 63.960, P < 0.01). Reactive cells increased gradually according to the regeneration of the epithelium, and were nearly equivalent to the normal side 6 weeks later without significant differentiation (t = 2.600, P > 0.05), according to the absolute positive cells in the operated and unoperated side of (417.8 +/- 32.4) and (445.3 +/- 10.0) respectively. The regeneration of the sensory neurons and receptors, both the number and the distribution, can recover to normal after olfactory nerve transection.