Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.

TNF-α-converting enzyme, a member of the ADAM (A disintegrin and metalloproteinase) protease family and also known as ADAM17, regulates inflammation and regeneration in health and disease. ADAM17 targets are involved in pain development and hypersensitivity in animal models of inflammatory and neuropathic pain. However, the role of ADAM17 in the pain pathway is largely unknown. Therefore, we used the hypomorphic ADAM17 (ADAM17ex/ex) mouse model to investigate the importance of ADAM17 in nociceptive behavior, morphology, and function of primary afferent nociceptors. ADAM17ex/ex mice were hyposensitive to noxious stimulation, showing elevated mechanical thresholds as well as impaired heat and cold sensitivity. Despite these differences, skin thickness and innervation were comparable to controls. Although dorsal root ganglia of ADAM17ex/ex mice exhibited normal morphology of peptidergic and nonpeptidergic neurons, a small but significant reduction in the number of isolectin ß-4-positive neurons was observed. Functional electrical properties of unmyelinated nociceptors showed differences in resting membrane potential, afterhyperpolarization, and firing patterns in specific subpopulations of sensory neurons in ADAM17ex/ex mice. However, spinal cord morphology and microglia activity in ADAM17ex/ex mice were not altered. Our data suggest that ADAM17 contributes to the processing of painful stimuli, with a complex mode of action orchestrating the function of neurons along the pain pathway.-Quarta, S., Mitric, M., Kalpachidou, T., Mair, N., Schiefermeier-Mach, N., Andratsch, M., Qi, Y., Langeslag, M., Malsch, P., Rose-John, S., Kress, M. Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States.

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics.

High-voltage-activated calcium current subtypes in mouse DRG neurons adapt in a subpopulation-specific manner after nerve injury.

Changes in ion channel function and expression are characteristic of neuropathic pain. Voltage-gated calcium channels (VGCCs) are integral for neurotransmission and membrane excitability, but relatively little is known about changes in their expression after nerve injury. In this study, we investigate whether peripheral nerve ligation is followed by changes in the density and proportion of high-voltage-activated (HVA) VGCC current subtypes in dorsal root ganglion (DRG) neurons, the contribution of presynaptic N-type calcium channels in evoked excitatory postsynaptic currents (EPSCs) recorded from dorsal horn neurons in the spinal cord, and the changes in expression of mRNA encoding VGCC subunits in DRG neurons. Using C57BL/6 mice [8- to 11-wk-old males (n = 91)] for partial sciatic nerve ligation or sham surgery, we performed whole cell patch-clamp recordings on isolated DRG neurons and dorsal horn neurons and measured the expression of all VGCC subunits with RT-PCR in DRG neurons. After nerve injury, the density of P/Q-type current was reduced overall in DRG neurons. There was an increase in the percentage of N-type and a decrease in that of P/Q-type current in medium- to large-diameter neurons. No changes were found in the contribution of presynaptic N-type calcium channels in evoked EPSCs recorded from dorsal horn neurons. The α2δ-1 subunit was upregulated by 1.7-fold and γ-3, γ-2, and ß-4 subunits were all downregulated 1.7-fold in injured neurons compared with sham-operated neurons. This comprehensive characterization of HVA VGCC subtypes in mouse DRG neurons after nerve injury revealed changes in N- and P/Q-type current proportions only in medium- to large-diameter neurons.

Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature.

Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted.

Polarization-sensitive descending neurons in the locust: connecting the brain to thoracic ganglia.

Many animal species, in particular insects, exploit the E-vector pattern of the blue sky for sun compass navigation. Like other insects, locusts detect dorsal polarized light via photoreceptors in a specialized dorsal rim area of the compound eye. Polarized light information is transmitted through several processing stages to the central complex, a brain area involved in the control of goal-directed orientation behavior. To investigate how polarized light information is transmitted to thoracic motor circuits, we studied the responses of locust descending neurons to polarized light. Three sets of polarization-sensitive descending neurons were characterized through intracellular recordings from axonal fibers in the neck connectives combined with single-cell dye injections. Two descending neurons from the brain, one with ipsilaterally and the second with contralaterally descending axon, are likely to bridge the gap between polarization-sensitive neurons in the brain and thoracic motor centers. In both neurons, E-vector tuning changed linearly with daytime, suggesting that they signal time-compensated spatial directions, an important prerequisite for navigation using celestial signals. The third type connects the suboesophageal ganglion with the prothoracic ganglion. It showed no evidence for time compensation in E-vector tuning and might play a role in flight stabilization and control of head movements.

Low-affinity CCK-A receptors are coexpressed with leptin receptors in rat nodose ganglia: implications for leptin as a regulator of short-term satiety.

The paradigm for the control of feeding behavior has changed significantly. Research has shown that leptin, in the presence of CCK, may mediate the control of short-term food intake. This interaction between CCK and leptin occurs at the vagus nerve. In the present study, we aimed to characterize the interaction between CCK and leptin in the vagal primary afferent neurons. Single neuronal discharges of vagal primary afferent neurons innervating the gastrointestinal tract were recorded from rat nodose ganglia. Three groups of nodose ganglia neurons were identified: group 1 responded to CCK-8 but not leptin; group 2 responded to leptin but not CCK-8; group 3 responded to high-dose CCK-8 and leptin. In fact, the neurons in group 3 showed CCK-8 and leptin potentiation, and they responded to gastric distention. To identify the CCK-A receptor (CCKAR) affinity states that colocalize with the leptin receptor OB-Rb, we used CCK-JMV-180, a high-affinity CCKAR agonist and low-affinity CCKAR antagonist. As expected, immunohistochemical studies showed that CCK-8 administration significantly potentiated the increase in the number of c-Fos-positive neurons stimulated by leptin in vagal nodose ganglia. Administration of CCK-JMV-180 eliminated the synergistic interaction between CCK-8 and leptin. We conclude that both low- and high-affinity CCKAR are expressed in nodose ganglia. Many nodose neurons bearing low-affinity CCKAR express OB-Rb. These neurons also respond to mechanical distention. An interaction between CCKAR and OB-Rb in these neurons likely facilitates leptin mediation of short-term satiety.

Biophysical basis for three distinct dynamical mechanisms of action potential initiation.

Transduction of graded synaptic input into trains of all-or-none action potentials (spikes) is a crucial step in neural coding. Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties. Despite widespread use of this classification scheme, a generalizable explanation of its biophysical basis has not been described. We recorded from spinal sensory neurons representing each class and reproduced their transduction properties in a minimal model. With phase plane and bifurcation analysis, each class of excitability was shown to derive from distinct spike initiating dynamics. Excitability could be converted between all three classes by varying single parameters; moreover, several parameters, when varied one at a time, had functionally equivalent effects on excitability. From this, we conclude that the spike-initiating dynamics associated with each of Hodgkin's classes represent different outcomes in a nonlinear competition between oppositely directed, kinetically mismatched currents. Class 1 excitability occurs through a saddle node on invariant circle bifurcation when net current at perithreshold potentials is inward (depolarizing) at steady state. Class 2 excitability occurs through a Hopf bifurcation when, despite net current being outward (hyperpolarizing) at steady state, spike initiation occurs because inward current activates faster than outward current. Class 3 excitability occurs through a quasi-separatrix crossing when fast-activating inward current overpowers slow-activating outward current during a stimulus transient, although slow-activating outward current dominates during constant stimulation. Experiments confirmed that different classes of spinal lamina I neurons express the subthreshold currents predicted by our simulations and, further, that those currents are necessary for the excitability in each cell class. Thus, our results demonstrate that all three classes of excitability arise from a continuum in the direction and magnitude of subthreshold currents. Through detailed analysis of the spike-initiating process, we have explained a fundamental link between biophysical properties and qualitative differences in how neurons encode sensory input.

A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors.

Despite increasing evidence for transcriptional control of neural connectivity, how transcription factors regulate discrete steps in axon guidance remains obscure. Projection neurons in the dorsal spinal cord relay sensory signals to higher brain centers. Some projection neurons send their axons ipsilaterally, whereas others, commissural neurons, send axons contralaterally. We show that two closely related LIM homeodomain proteins, Lhx2 and Lhx9, are expressed by a set of commissural relay neurons (dI1c neurons) and are required for the dI1c axon projection. Midline crossing by dI1c axons is lost in Lhx2/9 double mutants, a defect that results from loss of expression of Rig-1 from dI1c axons. Lhx2 binds to a conserved motif in the Rig-1 gene, suggesting that Lhx2/9 regulate directly the expression of Rig-1. Our findings reveal a link between the transcriptional programs that define neuronal subtype identity and the expression of receptors that guide distinctive aspects of their trajectory.

Temporal processing across multiple topographic maps in the electrosensory system.

Multiple topographic representations of sensory space are common in the nervous system and presumably allow organisms to separately process particular features of incoming sensory stimuli that vary widely in their attributes. We compared the response properties of sensory neurons within three maps of the body surface that are arranged strictly in parallel to two classes of stimuli that mimic prey and conspecifics, respectively. We used information-theoretic approaches and measures of phase locking to quantify neuronal responses. Our results show that frequency tuning in one of the three maps does not depend on stimulus class. This map acts as a low-pass filter under both conditions. A previously described stimulus-class-dependent switch in frequency tuning is shown to occur in the other two maps. Only a fraction of the information encoded by all neurons could be recovered through a linear decoder. Particularly striking were low-pass neurons the information of which in the high-frequency range could not be decoded linearly. We then explored whether intrinsic cellular mechanisms could partially account for the differences in frequency tuning across maps. Injection of a Ca2+ chelator had no effect in the map with low-pass characteristics. However, injection of the same Ca2+ chelator in the other two maps switched the tuning of neurons from band-pass/high-pass to low-pass. These results show that Ca2+-dependent processes play an important part in determining the functional roles of different sensory maps and thus shed light on the evolution of this important feature of the vertebrate brain.

Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation.

The c-kit receptor tyrosine kinase is expressed in a subpopulation of small- and medium-sized neurons of the dorsal root ganglia (DRG) and in the superficial layer of the spinal cord. Stem cell factor (SCF), a ligand of the c-kit receptor, induces neurite outgrowth from DRG and supports the survival of c-kit-expressing neurons. To clarify the possible function of the SCF/c-kit receptor system in the adult animal, we investigated the expression of c-kit receptor in the spinal cord and DRG in relation to pain by using H2C7, a newly developed anti-c-kit monoclonal antibody. S.c. and intrathecal injection of SCF markedly reduced the paw withdrawal threshold to mechanical stimuli and intrathecal SCF at 10 pg maximally induced mechanical allodynia in conscious mice. Intrathecal SCF also reduced the paw withdrawal latency to heat stimuli significantly but transiently. The c-kit receptor was co-expressed in 58.4% of calcitonin gene-related peptide (CGRP) -positive, but only 5.1% of isolectin B4-positive, DRG neurons. In the spinal cord, the c-kit receptor was detected in the superficial layer of the dorsal horn and co-localized there with CGRP in central terminals of DRG neurons. Selective elimination of unmyelinated C-fibers by neonatal capsaicin treatment resulted in marked reduction of the c-kit receptor and CGRP expression in the superficial layer of the spinal cord. Cell-size profiles showed that c-kit receptor expression was significantly up-regulated and down-regulated in medium-sized DRG neurons after neonatal capsaicin treatment and nerve injury, respectively. These results suggest that the c-kit receptor is mainly expressed in peptidergic small-sized DRG neurons and may be involved in pain regulation both peripherally and centrally.

Bladder afferent sensitivity in wild-type and TRPV1 knockout mice.

Understanding bladder afferent pathways may reveal novel targets for therapy of lower urinary tract disorders such as overactive bladder syndrome and cystitis. Several potential candidate molecules have been postulated as playing a significant role in bladder function. One such candidate is the transient receptor potential vanilloid 1 (TRPV1) ion channel. Mice lacking the TRPV1 channel have altered micturition thresholds suggesting that TRPV1 channels may play a role in the detection of bladder filling. The aim of this study was therefore to investigate the role of TRPV1 receptors in controlling bladder afferent sensitivity in the mouse using pharmacological receptor blockade and genetic deletion of the channel. Multiunit afferent activity was recorded in vitro from bladder afferents taken from wild-type (TRPV+/+) mice and knockout (TRPV1-/-) mice. In wild-type preparations, ramp distension of the bladder to a maximal pressure of 40 mmHg produced a graded increase in afferent activity. Bath application of the TRPV1 antagonist capsazepine (10 mum) caused a significant attenuation of afferent discharge in TRPV1+/+ mice. Afferent responses to distension were significantly attenuated in TRPV1-/- mice in which sensitivity to intravesical hydrochloric acid (50 mm) and capsaicin (10 microm) were also blunted. Altered mechanosensitivity occurred in the absence of any changes in the pressure-volume relationship during filling indicating that this was not secondary to a change in bladder compliance. Single-unit analysis was used to classify individual afferents into low-threshold and high-threshold fibres. Low threshold afferent responses were attenuated in TRPV1-/- mice compared to the TRPV1+/+ littermates while surprisingly high threshold afferent sensitivity was unchanged. While TRPV1 channels are not considered to be mechanically gated, the present study demonstrates a clear role for TRPV1 in the excitability of particularly low threshold bladder afferents. This suggests that TRPV1 may play an important role in normal bladder function.

Expression of TWIK-related acid sensitive K+ channels in capsaicin sensitive and insensitive cells of rat dorsal root ganglia.

Previous reports have demonstrated that small- to medium-diameter dorsal root ganglia (DRG) cells in rats can be subgrouped into individual cell types by patterns of voltage-activated currents. These cell types have consistent responses to algesic compounds and maintain characteristic histochemical phenotypes. Using immunocytochemical methods, we have now examined expression of TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related acid sensitive K+ (TASK) channels, TASK-1, TASK-2 and TASK-3, in nine electrophysiologically identified small- to medium-diameter DRG cell types. The immunoreactivity in DRG cells was diverse, with all nine cell types expressing one to all three TASK channels. Some cells expressed TASK-1 (types 1, 4, 6 and 9), some TASK-2 (types 2, 4, 5, 6, 7 and 9), and some TASK-3 (types 1, 2, 3, 4, 5, 6 and 8). The co-expression of TASK-1 and TASK-3 in cell types 1, 4 and 6 suggests that these sensory afferents might contain functional heterodimeric channels. In peripheral sensory afferents, TASK channels have been implicated in the pain sensory transduction pathway, and can be modulated by anesthetics and neuroprotective agents. This study seeks to identify TASK channel populations in electrophysiologically characterized populations of putative nociceptive afferents.

Major classes of sensory neurons to the urinary bladder.

A novel in vitro bladder preparation was used to examine effect of various stimuli (stretch, von Frey hair compression, stroking of receptive fields, applications of chemical stimuli to the mucosa) on electrophysiological recordings from guinea pig bladder afferents in vitro. Several functionally distinct classes of bladder sensory neurons were distinguished. These include stretch-sensitive afferents-muscle mechanoreceptors which behaved as "in-series tension receptors" and tension-mucosal mechanoreceptors, which could be activated by stretch, mucosal stroking with light von Frey hair (0.1-2 mN) and by hypertonic solutions (1 M mannitol and 490-850 mM NaCl) applied locally to their receptive fields in the mucosa. In addition, we have recorded stretch-insensitive afferents-mucosal mechanoreceptors and chemoreceptors. The non-selective P2X/P2Y purinoreceptor antagonist, PPADS (30 microM) did not affect stretch-induced firing by low threshold muscle mechanoreceptors but significantly inhibited alpha,beta-methylene ATP (30 microM)-induced contractions and associated afferent firing. Transduction by low threshold stretch-sensitive muscle mechanoreceptors does not appear to involve exocytotic synaptic transmission since it occurs in Ca2+-free (with 1 mM EDTA and 6 mM Mg2+) Krebs solution. The data suggest that the endogenous transmitter ATP is not involved in mechanotransduction by this specific class of low threshold muscle mechanoreceptors in the guinea pig bladder; rather they appear to transduce mechanical stimuli directly, possibly via stretch-activated ion channels. Mechanisms of activation of other classes of mechanoreceptors and chemoreceptors remain to be established.

"Runx"ing towards sensory differentiation.

Somatosensory stimuli are encoded by molecularly and anatomically diverse classes of dorsal root ganglia (DRG) neurons. In this issue of Neuron, three papers demonstrate that the Runx transcription factors, Runx1 and Runx3, respectively regulate the molecular identities and spinal terminations of TrkA+ nociceptive neurons and TrkC+ proprioceptive neurons. These findings emphasize the importance of intrinsic genetic programs in generating the diversity of DRG neurons and specifying the circuits into which they incorporate.

A role for Runx transcription factor signaling in dorsal root ganglion sensory neuron diversification.

Subpopulations of sensory neurons in the dorsal root ganglion (DRG) can be characterized on the basis of sensory modalities that convey distinct peripheral stimuli, but the molecular mechanisms that underlie sensory neuronal diversification remain unclear. Here, we have used genetic manipulations in the mouse embryo to examine how Runx transcription factor signaling controls the acquisition of distinct DRG neuronal subtype identities. Runx3 acts to diversify an Ngn1-independent neuronal cohort by promoting the differentiation of proprioceptive sensory neurons through erosion of TrkB expression in prospective TrkC+ sensory neurons. In contrast, Runx1 controls neuronal diversification within Ngn1-dependent TrkA+ neurons by repression of neuropeptide CGRP expression and controlling the fine pattern of laminar termination in the dorsal spinal cord. Together, our findings suggest that Runx transcription factor signaling plays a key role in sensory neuron diversification.

Graded activity of transcription factor Runx3 specifies the laminar termination pattern of sensory axons in the developing spinal cord.

Different functional classes of dorsal root ganglion sensory neurons project their axons to distinct target zones within the developing spinal cord. To explore the mechanisms that link sensory neuron subtype identity and axonal projection pattern, we analyzed the roles of Runx and ETS transcription factors in the laminar targeting of sensory afferents. Gain- and loss-of-function studies in chick embryos reveal that the status of Runx3 expression is a major determinant of the dorso-ventral position of termination of proprioceptive and cutaneous sensory axons. In addition, the level of expression and/or activity of Runx3 in individual proprioceptive sensory neurons appears to specify whether their axons terminate in intermediate or ventral regions. Our findings suggest that the selectivity of Runx3 expression, and its level of activity, control sensory afferent targeting in the developing spinal cord.

Differential responses of bladder lumbosacral and thoracolumbar dorsal root ganglion neurons to purinergic agonists, protons, and capsaicin.

The present study explored differences in sensitivity to purinergic agonists, protons, and capsaicin in lumbosacral (LS) and thoracolumbar (TL) sensory neurons that innervate the rat urinary bladder. The majority of LS neurons (93%) were sensitive to alpha,beta-methyleneATP (alpha,beta-metATP) compared with 50% of TL neurons. Based on inactivation kinetics, a slowly desensitizing current evoked by alpha,beta-metATP predominated in LS neurons (86%) compared with mixed components that characterized TL neuron responses (58%). The density of the slowly desensitizing current was greater in LS than in TL neurons (LS, 34.4 +/- 5.3 pA/pF; TL, 2.5 +/- 0.8 pA/pF). Almost all neurons in both ganglia responded to protons and to capsaicin (LS, 100%; TL, 98%). Proton-activated currents in bladder sensory neurons exhibited distinct inactivation kinetics as fast, intermediate, slowly desensitizing, and sustained components. More than one component was expressed in every cell. Although there was no difference in the percentage of neurons expressing more than one component, the density of the sustained current was significantly greater in LS than in TL neurons (LS, 86.1 +/- 16 pA/pF; TL, 30.3 +/- 7 pA/pF). Similarly, the capsaicin-evoked current was greater in LS than in TL neurons (LS, 129.6 +/- 17 pA/pF; TL, 86.9 +/- 11 pA/pF). Finally, a greater percentage of TL neurons bound isolectin B4 than LS neurons (LS, 61%; TL, 85%). The greater degree of alpha,beta-metATP, proton, and capsaicin responsiveness, in addition to differences in current type and current densities, in LS and TL neurons suggests that bladder pelvic and hypogastric/lumbar splanchnic afferents are functionally distinct and likely mediate different sensations arising from the urinary bladder.

Quantitative aspects of the spatial distribution and morphological characteristics of the sea bass (Dicentrarchus labrax L.; Teleostei, Serranidae) trunk lateral line neuromasts.

The results presented herein report quantitative data relative to the distribution and morphological characteristics of both types of neuromasts encountered on the trunk lateral line of the sea bass (Dicentrarchus labrax, L.). These data were obtained from scanning electron micrographs. They indicate that, as expected, each modified scale of the sea bass possessed a single canal neuromast with long axis oriented parallel to the fish's long axis. In contrast to several fish species, two thirds of superficial neuromasts observed herein were oriented perpendicular to the fish's long axis. However, whatever the main orientation of superficial neuromasts, two thirds of their hair bundles were oriented parallel to the long axis of the animal with approximately half of them in the direction of the head. Similar ratios were observed for canal neuromasts whatever the area of the maculae: central or peripheral. For both types of neuromasts it was not possible to clearly distinguish a paired organization of hair bundles with opposing polarities. Superficial neuromasts on each trunk canal scale were located on either the dorsal or ventral side of the canal and appeared to be distributed along the trunk lateral line with a higher probability to be encountered closer to the operculum. The frequency of presence and the average number of superficial neuromasts per scale increased with fish size. We observed a size gradient for canal neuromasts between the operculum and caudal peduncle. This gradation was correlated with a reduction of the width of the central area of the canal segment. Canal neuromasts were always localized in the larger portions of the canal segments. Taken together, these results point out some specific features associated with the sea bass trunk lateral line. With the previous report, they establish the first full description of the trunk lateral line of sea bass and will be useful for upcoming experiments regarding the function of the two types of neuromasts.

Amphiregulin acts as an autocrine survival factor for adult sensory neurons.

We studied the effect of amphiregulin on axonal outgrowth and survival in sensory neurons in organ cultured and dissociated mouse dorsal root ganglia (DRG). Amphiregulin at 20 ng/ml stimulated axonal outgrowth in both preparations. The EGF receptor inhibitor AG1478 inhibited outgrowth at 10 microM but not at 1 microM, where it abolished the stimulatory effects of amphiregulin. Fluoro-Jade staining and neuronal counting showed that more neurons survived in culture in the presence of amphiregulin while AG1478 at 10 microM but not 1 microM increased cell death. Small and medium sized neurons were immunopositive for both amphiregulin and the EGF receptor. Taken together these results suggest that amphiregulin can act as an autocrine survival factor for sensory neurons and stimulate axonal outgrowth through the EGF receptor.

Enhanced excitability of dissociated primary sensory neurons after chronic compression of the dorsal root ganglion in the rat.

A chronic compression of the dorsal root ganglion (CCD) produces ipsilateral cutaneous hyperalgesia and allodynia in rats. Intracellular electrophysiological recordings from formerly compressed neurons in the intact dorsal root ganglion (DRG) reveal lower than normal current thresholds (CTs) and abnormal spontaneous activity (SA) (Zhang JM, Song XJ, LaMotte RH. Enhanced excitability of sensory neurons in rats with cutaneous hyperalgesia produced by chronic compression of the dorsal root ganglion. J Neurophysiol 1999;82:3359-66). To determine if the neuronal hyperexcitability is intrinsic to the soma, L4 and L5 DRG neurons from rats that had prior CCD surgery or those that did not (controls) were dissociated, and intracellular recordings obtained 3-8 h (acute) or 24-30 h (1d) after culture. The CTs of large- (>45 microm diameter) and medium- (30 approximately 45 microm) sized neurons from control rats after acute or 1d culture were similar to those formerly recorded from the intact DRG and significantly lower for CCD than for control rats. However, the CTs of small- (