Increase In Magnitude Of Response Research Articles

Multiple-stressors effects on Iberian freshwaters: A review of current knowledge and future research priorities

Freshwater ecosystems are exposed to an increasing number of stressors, challenging their biomonitoring and management. Despite recent advances in multiple-stressor research, regional-scale assessments in areas with high freshwater biodiversity and increasing anthropogenic pressure are urgently needed. We reviewed 61 studies focused on freshwater individuals, populations and communities from the Iberian Peninsula to (i) quantify the frequency of experimental approaches used (manipulative, observational), aquatic systems, biological organization levels, and types of organisms and modelled responses, (ii) identify key individual stressors and the frequency of significant positive (increase in response magnitude) and negative (decrease) effects and (iii) determine types of interacting stressors and the frequency of their combined effects. Our dataset comprised 409 unique responses to 13 types of individual stressors, 34 stressor pairs and 12 high-order interactions (3- and 4-way). We found a higher prevalence of manipulative (85 %) respect to observational studies, and a greater focus on lotic systems (59 %) and heterotrophic organisms (58 %). The most studied stressors were nutrient (Nutr), thermal (Therm), hydrologic (Hydr), ultraviolet radiation (UVR), toxic (Toxic) and salinity (Sal) stress and land-use pressure. Individual stressors showed a higher proportion of negative (34 %) than positive effects (26 %). Nutr × UVR, Toxic × Toxic, Therm × Toxic, Hydr × Toxic, Sal × Therm, and Nutr × Therm were the most studied stressor pairs. Non-interactive (50 %) and interactive responses (50 %) were balanced. Antagonistic effects (18 %) were slightly more common than synergisms (15 %), reversal or opposing (13 %) and high-order interactions (4 %). Such proportions varied within experimental approaches, biological organization levels and organism types. Our findings are helpful to manage certain stressor combinations in Iberian freshwaters. Further efforts in Iberian multiple-stressor research should be directed to (i) intensify the study of lentic systems, (ii) explore more observational data, (iii) autotrophic organisms and (vi) biodiversity-ecosystem functioning responses, and (v) cover a wider range of stressors and (vi) more complex interacting stressor scenarios.

Palladium Nanosheet-Based Dual Gas Sensors for Sensitive Room-Temperature Hydrogen and Carbon Monoxide Detection.

Palladium has long been explored for use in gas sensors because of its excellent catalytic properties and its unique property of forming hydrides in the presence of H2. However, pure Pd-based sensors usually suffer from low response and a relatively high limit of detection. Palladium nanosheets (PdNS) are of particular interest for gas sensing applications due to their high surface area and excellent electrical conductivity. Here, we demonstrate the design and fabrication of low-cost PdNS-based dual gas sensors for room-temperature detection of H2 and CO over a wide concentration range. We fabricated sensors using multiwalled carbon nanotube@PdNS (MWCNT@PdNS) composites and compared their performance against pure PdNS devices for hydrogen sensing based on electrical resistive response. Devices using PdNS alone had a response and response time of 0.4% and 50 s, respectively, to 1% H2 in air. MWCNT@PdNS (1:5 mass ratio) showed enhanced performance at a lower hydrogen concentration with a limit of detection (LODH2) of 5 ppm. Nearly an order of magnitude increase in response was observed on increasing the amount of MWCNT to 50 mass % in the nanocomposite, but the response fell off at low H2 concentration. Overall, these PdNS-based sensors were found to show good repeatability, stability, and performance under humid conditions. Their response was selective for H2versus CH4, CO2, and NH3; the response to CO was comparable in magnitude but opposite in sign to the response to H2. Upon simultaneous exposure to equal concentrations (10 ppm each) of H2 and CO, the response to CO was dominant. The PdNS showed high sensitivity to CO, detecting as little as 1 ppm CO in air at room temperature. The sensitivity to CO could be used either in a stand-alone room-temperature CO detector, where H2 is known not to be present, or in combination with CO and combustible gas detectors to distinguish H2 from other combustible gases.

Different word-learning contexts alter phonotactic rule learning in 6-month-olds

ABSTRACT Context can affect language processing and learning. We here compare the influence of two different contexts (pseudo-objects, data from [Obrig, H., Mock, J., Stephan, F., Richter, M., Vignotto, M., & Rossi, S. (2017). Impact of associative word learning on phonotactic processing in 6-month-old infants: A combined EEG and fNIRS study. Developmental Cognitive Neuroscience, 25, 185–197. https://doi.org/10.1016/j.dcn.2016.09.001] , vs. real objects) on the processing of phonotactically legal vs. illegal pseudowords (PW) in a 3-day learning paradigm in 6-month-olds. Using ERPs and functional Near InfraRed Spectroscopy (fNIRS) we find that short-term (pre-→post-test) and long-term (day1→ day2→day3) attunement to pseudowords is affected by both, learning context and phonotactic status. When real objects are used, fNIRS shows a long-term increase in response magnitude for legal PW. ERPs show a long-term decrease in negativities in response to trained legal PW. Conversely, the pseudo-objects context elicits neuronal attunement to all PW. We propose that legal PW in a real object context cause conflict, leading to difficulties in lexical integration. However, training eases lexical integration of trained legal PW through priming. Our results speak for the early relevance of phonotactics and context in language acquisition.

Evaluating Baseline and Sensitised Heat Nociception in Adult Drosophila.

Chronic pain is a complex disease that affects a large proportion of the population. With little to no effective treatments currently available for patients, this malady presents a large burden to society. Drosophila melanogaster has been previously used to describe conserved molecular components of nociception in larvae and adults. However, adult assays tend to rely on avoidance behaviours, and whilst larval acute thermal avoidance assays exist, larvae are not best suited to a chronic pain scenario as the condition must be long-term. Therefore, an adult thermal nociception response assay was required to study injury-evoked changes in heat nociception threshold (allodynia and hyperalgesia) over time, and we describe such a protocol here. Following leg amputation, flies display increased thermal sensitivity (allodynia) to innocuous temperatures but not an increase in magnitude of response (hyperalgesia) to noxious heat. Our method allows for individualised analysis of both allodynia and hyperalgesia.

Highly sensitive sensors based on quasi-2D rGO/SnS2 hybrid for rapid detection of NO2 gas

Nitrogen dioxide (NO2) sensing is important in terms of the agriculture development and healthcare monitoring. However, relatively poor recovery kinetics at a low temperature is still a problem for NO2 sensing and remains to be solved. In this work, we combine the excellent sensing properties and gas adsorption capacity of two- dimensional (2D) tin disulfide (SnS2) hexagonal nanoflakes with the beneficial electrical properties of graphene to build high-performance NO2 sensors by a simple and low-cost method. We found that the sensors based on the quasi-2D rGO-SnS2 hybrids exhibited exclusive selectivity towards NO2. The presence of rGO in hybrids decreased optimal working temperature effectively. Sensors based on 0.8% rGO-SnS2 (G-SS) show almost an order of magnitude increase in response (32) compared to pristine SnS2 (3.5). Especially, the response/recovery time is 50/48 s, respectively, demonstrating the favorable response/recovery kinetics of sensors. Such significant features can be attributed to the synergistic effect of the quasi-2D G-SS hybrid and the local heterojunctions in the interface between SnS2 and rGO.

Th17 responses to pneumococcus in blood and adenoidal cells in children.

Pneumococcal infections cause a large global health burden, and the search for serotype-independent vaccines continues. Existing conjugate vaccines reduce nasopharyngeal colonization by target serotypes. Such mucosal effects of novel antigens may similarly be important. CD4+ Th17 cell-dependent, antibody-independent reductions in colonization and enhanced clearance have been described in mice. Here we describe the evaluation of T helper type 17 (Th17) cytokine responses to candidate pneumococcal protein vaccine antigens in human cell culture, using adenoidal and peripheral blood mononuclear cells. Optimal detection of interleukin (IL)-17A was at day 7, and of IL-22 at day 11, in these primary cell cultures. Removal of CD45RO+ memory T cells abolished these responses. Age-associated increases in magnitude of responses were evident for IL-17A, but not IL-22, in adenoidal cells. There was a strong correlation between individual IL-17A and IL-22 responses after pneumococcal antigen stimulation (P<0·015). Intracellular cytokine staining following phorbol myristate acetate (PMA)/ionomycin stimulation demonstrated that >30% CD4+ T cells positive for IL-22 express the innate markers γδT cell receptor and/or CD56, with much lower proportions for IL-17A+ cells (P<0·001). Responses to several vaccine candidate antigens were observed but were consistently absent, particularly in blood, to PhtD (P<0·0001), an antigen recently shown not to impact colonization in a clinical trial of a PhtD-containing conjugate vaccine in infants. The data presented and approach discussed have the potential to assist in the identification of novel vaccine antigens aimed at reducing pneumococcal carriage and transmission, thus improving the design of empirical clinical trials.

Regulatory T Cells Suppress Effector T Cell Proliferation by Limiting Division Destiny.

Understanding how the strength of an effector T cell response is regulated is a fundamental problem in immunology with implications for immunity to pathogens, autoimmunity, and immunotherapy. The initial magnitude of the T cell response is determined by the sum of independent signals from antigen, co-stimulation and cytokines. By applying quantitative methods, the contribution of each signal to the number of divisions T cells undergo (division destiny) can be measured, and the resultant exponential increase in response magnitude accurately calculated. CD4+CD25+Foxp3+ regulatory T cells suppress self-reactive T cell responses and limit pathogen-directed immune responses before bystander damage occurs. Using a quantitative modeling framework to measure T cell signal integration and response, we show that Tregs modulate division destiny, rather than directly increasing the rate of death or delaying interdivision times. The quantitative effect of Tregs could be mimicked by modulating the availability of stimulatory co-stimuli and cytokines or through the addition of inhibitory signals. Thus, our analysis illustrates the primary effect of Tregs on the magnitude of effector T cell responses is mediated by modifying division destiny of responding cell populations.

How Configural Is the Configural Superiority Effect? A Neuroimaging Investigation of Emergent Features in Visual Cortex.

The perception of a visual stimulus is dependent not only upon local features, but also on the arrangement of those features. When stimulus features are perceptually well organized (e.g., symmetric or parallel), a global configuration with a high degree of salience emerges from the interactions between these features, often referred to as emergent features. Emergent features can be demonstrated in the Configural Superiority Effect (CSE): presenting a stimulus within an organized context relative to its presentation in a disarranged one results in better performance. Prior neuroimaging work on the perception of emergent features regards the CSE as an “all or none” phenomenon, focusing on the contrast between configural and non-configural stimuli. However, it is still not clear how emergent features are processed between these two endpoints. The current study examined the extent to which behavioral and neuroimaging markers of emergent features are responsive to the degree of configurality in visual displays. Subjects were tasked with reporting the anomalous quadrant in a visual search task while being scanned. Degree of configurality was manipulated by incrementally varying the rotational angle of low-level features within the stimulus arrays. Behaviorally, we observed faster response times with increasing levels of configurality. These behavioral changes were accompanied by increases in response magnitude across multiple visual areas in occipito-temporal cortex, primarily early visual cortex and object-selective cortex. Our findings suggest that the neural correlates of emergent features can be observed even in response to stimuli that are not fully configural, and demonstrate that configural information is already present at early stages of the visual hierarchy.

Statistical context shapes stimulus-specific adaptation in human auditory cortex.

Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity.

A mechanical model of the gating spring mechanism of stereocilia

The stereocilium is the basic sensory unit of nature's mechanotransducers, which include the cochlear and vestibular organs. In noisy environments, stereocilia display high sensitivity to miniscule stimuli, effectively dealing with a situation that is a design challenge in micro systems. The gating spring hypothesis suggests that the mechanical stiffness of stereocilia bundle is softened by tip-link gating in combination with active bundle movement, contributing to the nonlinear amplification of miniscule stimuli. To demonstrate that the amplification is induced mechanically by the gating as hypothesized, we developed a biomimetic model of stereocilia and fabricated the model at the macro scale. The model consists of an inverted pendulum array with bistable buckled springs at its tips, which represent the mechanically gated ion channel. Model simulations showed that at the moment of gating, instantaneous stiffness softening generates an increase in response magnitude, which then sequentially occurs as the number of gating increases. This amplification mechanism appeared to be robust to the change of model parameters. Experimental data from the fabricated macro model also showed a significant increase in the open probability and pendulum deflection at the region having a smaller input magnitude. The results demonstrate that the nonlinear amplification of miniscule stimuli is mechanically produced by stiffness softening from channel gating.

Exercise Induces Cortical Plasticity after Neonatal Spinal Cord Injury in the Rat

Exercise-induced cortical plasticity is associated with improved functional outcome after brain or nerve injury. Exercise also improves functional outcomes after spinal cord injury, but its effects on cortical plasticity are not known. The goal of this investigation was to study the effect of moderate exercise (treadmill locomotion, 3 min/d, 5 d/week) on the somatotopic organization of forelimb and hindlimb somatosensory cortex (SI) after neonatal thoracic transection. We used adult rats spinalized as neonates because some of these animals develop weight-supported stepping, and, therefore, the relationship between cortical plasticity and stepping could also be examined. Acute, single-neuron mapping was used to determine the percentage of cortical cells responding to cutaneous forelimb stimulation in normal, spinalized, and exercised spinalized rats. Multiple single-neuron recording from arrays of chronically implanted microwires examined the magnitude of response of these cells in normal and exercised spinalized rats. Our results show that exercise not only increased the percentage of responding cells in the hindlimb SI but also increased the magnitude of the response of these cells. This increase in response magnitude was correlated with behavioral outcome measures. In the forelimb SI, neonatal transection reduced the percentage of responding cells to forelimb stimulation, but exercise reversed this loss. This restoration in the percentage of responding cells after exercise was accompanied by an increase in their response magnitude. Therefore, the increase in responsiveness of hindlimb SI to forelimb stimulation after neonatal transection and exercise may be due, in part, to the effect of exercise on the forelimb SI.

Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters

Genetically encoded sensors of glutamate concentration are based on FRET between cyan and yellow fluorescent proteins bracketing a bacterial glutamate-binding protein. Such sensors have yet to find quantitative applications in neurons, because of poor response amplitude in physiological buffers or when expressed on the neuronal cell surface. We have improved our glutamate-sensing fluorescent reporter (GluSnFR) by systematic optimization of linker sequences and glutamate affinities. Using SuperGluSnFR, which exhibits a 6.2-fold increase in response magnitude over the original GluSnFR, we demonstrate quantitative optical measurements of the time course of synaptic glutamate release, spillover, and reuptake in cultured hippocampal neurons with centisecond temporal and spine-sized spatial resolution. During burst firing, functionally significant spillover persists for hundreds of milliseconds. These glutamate levels appear sufficient to prime NMDA receptors, potentially affecting dendritic spike initiation and computation. Stimulation frequency-dependent modulation of spillover suggests a mechanism for nonsynaptic neuronal communication.

Interactions between auditory and somatosensory feedback for voice F 0 control

Previous studies have demonstrated the importance of both kinesthetic and auditory feedback for control of voice fundamental frequency (F0). In the present study, a possible interaction between auditory feedback and kinesthetic feedback for control of voice F0 was tested by administering local anesthetic to the vocal folds in the presence of perturbations in voice pitch feedback. Responses to pitch-shifted voice feedback were larger when the vocal fold mucosa was anesthetized than during normal kinesthesia. A mathematical model incorporating a linear combination of kinesthesia and pitch feedback simulated the main aspects of our experimental results. This model indicates that a feasible explanation for the increase in response magnitude with vocal fold anesthesia is that the vocal motor system uses both pitch and kinesthesia to stabilize voice F0 shortly after a perturbation of voice pitch feedback has been perceived.

Effects of GABA A receptor inhibition on response properties of barrel cortical neurons in C-Fiber-depleted rats

C-fiber depletion results in expansion of low threshold somatosensory mechanoreceptive fields. In this study, we investigated the role of intact C-fibers in GABAA-mediated inhibition in barrel cortical neurons. We used electronically controlled mechanical stimulation of whiskers to quantitatively examine the responses of barrel cells to whisker displacements. After systemic injection of picrotoxin neuronal responses were recorded at 5 min intervals for 20 min and then at 10 min intervals for 100 min. Picrotoxin injection caused a 3-fold increase in response magnitude of adjacent whisker stimulation and 1.4-fold increase in response magnitude of principal whisker stimulation with a maximum enhancement 50 min after the injection. There was no significant change in spontaneous activity following picrotoxin injection. The response enhancement and receptive field expansion observed in normal rats were completely absent in the C-fiber-depleted rats. These results suggest that the GABAA-mediated inhibition that modulates the receptive field functional organization of the barrel cortex depends on intact C-fibers.

Responses of lateral line receptors to water flow in the Antarctic notothenioid, Trematomus bernacchii

The response properties of anterior lateral line afferent neurones in Trematomus bernacchii were recorded extracellularly while stimulating the fish with unidirectional water flows of varying velocity. Afferent neurone responses were either flow-sensitive or flow-insensitive. Flow-sensitive neurones showed linear increases in response magnitude with increasing flow rate and tonic non-adapting response properties. These findings indicate that flow-sensitive afferent neurones originate from lateral line receptors that detect absolute flow velocity. The likely explanation is that flow-sensitive afferent neurones innervate neuromasts located superficially on the skin and flow-insensitive neurones innervate neuromasts situated in sub-epidermal fluid-filled canals.

Inhibition has little effect on response latencies in the inferior colliculus.

The inferior colliculi of all mammals are characterized by a wide range of first-spike response latencies that can greatly exceed the minimum time required for the transmission of input through the lower brainstem. The mechanisms that account for long response latencies of up to 50 ms are unclear, but one hypothesis is that an early inhibition plays a role in shaping latency. To test this hypothesis, response latencies were measured in the inferior colliculi of the pallid and mustached bats before and during the blockade of GABAa and glycine receptors. The effect of blocking inhibition on response latency was compared under stimulus conditions that produced the shortest latency in the predrug condition. Multibarrel "piggyback" electrodes were used to iontophoretically apply bicuculline and strychnine sequentially while recording from single neurons. Predrug latencies ranged from 9 to 26 ms in the pallid bat and from 4 to 17 ms in the mustached bat. Despite large increases in response magnitude and response duration following disinhibition, the blockade of inhibitory receptors had modest effects on response latency. In the pallid bat, blocking GABA receptors produced latency changes that ranged from -3.8 to +0.2 ms, while blocking glycine receptors produced changes from -0.1 to +1.7 ms. Similarly, in the mustached bat, blocking GABA receptors caused changes ranging from -10.3 to +1.4 ms; blocking glycine receptors in the mustached bat caused changes from -3.6 to +1.0 ms. The large change of -10.3 ms was an exception. In both species, the majority of neurons showed changes of <1 ms. We conclude that a fast, early inhibitory input does not appear to play a significant role in shaping the wide range of response latencies present in the inferior colliculi of mustached and pallid bats.

Acute effect of an incision on mechanosensitive afferents in the plantar rat hindpaw.

The purpose of this study was to examine which primary afferent fibers are sensitized to mechanical stimuli after an experimental surgical incision to the glabrous skin of the rat hindpaw. Afferent fibers teased from the L(5) dorsal root or the tibial nerve were recorded in anesthetized rats. The mechanical response properties of each fiber were characterized before and 45 min after an incision (or sham procedure) within the mechanical receptive field. Sensitization is characterized by an expansion of the mechanical receptive field, an increase in background activity, an increase in response magnitude, or a decrease in response threshold. After incision, the background activity and response properties of Abeta-fibers (n = 9) to mechanical stimuli were unchanged. Four of 13 mechanosensitive Adelta-fibers exhibited sensitization after the incision; response threshold decreased, response magnitude increased, or receptive field size increased. Background activity of Adelta-fibers was not increased by the incision. Sensitization was observed in 4 of 18 mechanosensitive C-fibers 45 min after the incision. Background activity of C-fibers was not increased by the incision. In a group of mechanically insensitive afferent fibers (MIAs), 3 of 7 Adelta-fibers and 4 of 10 C-fibers sensitized 45 min after incision. Response threshold was decreased in only 2 of 17 MIAs; receptive field size increased in 7 of 17 MIAs. Abeta-fibers did not sensitize after the incision, and only 8 of 31 (26%) mechanosensitive Adelta- and C-fibers gave evidence of sensitization. In a group of MIA Adelta- and C-fibers, a greater percentage of 17 fibers studied (41%) were sensitized after incision. In this model, the principal effect of an incision, when examined 45 min after the insult, is an increase in receptive field size of the afferents, particularly those characterized as MIAs. To the extent that the mechanical hyperalgesia characterized in the same model is initiated in the periphery, it would appear that spatial summation of modestly increased response magnitude is important to the development of hyperalgesia.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Neurobiological concepts of fibromyalgia - the possible role of descending spinal tracts

In the spinal cord, long descending pathways are known to exist which modulate pain sensations by either inhibiting or facilitating the discharges of spinal nociceptive neurones. In this article, the hypothesis is discussed that the pain of fibromyalgia may be due to a dysfunction of these pain­modulating pathways. Theoretically, two kinds of disturbance could lead to pain, namely reduced activity in the pain­inhibiting (antinociceptive) system or increased activity in the pain­facilitating (pronociceptive) pathways. Data from animal experiments show that interruption of the dorsal descending systems leads to hyperactivity of spinal nociceptive neurones, namely increase in background activity, lowering in stimulation threshold, and increase in response magnitude to noxious stimuli. The responses of the neurones to input from nociceptors in deep tissues were more strongly inhibited by the descending pathways than were responses to input from cutaneous nociceptors. Collectively, the findings indicate that the dorsal descending systems are tonicly active and have a particularly strong inhibitory action on neurones that mediate pain from deep tissues. If these systems operate in a similar way also in patients, an impairment of their function is likely to lead to 1. spontaneous deep pain (because of an increased background activity in nociceptive neurones supplying deep tissues), 2. tenderness of deep tissues (because of a lowered mechanical threshold of the same neurones), and 3. hyperalgesia of deep tissues (because of increased neuronal responses to noxious stimuli). These changes will affect large areas of the body because the descending inhibitory systems have widespread terminations in the spinal cord. Thus, a dysfunction of the descending inhibitory pathways could mimick to a large extent the pain of fibromyalgia.

Striatal Neuronal Activity and Responsiveness to Dopamine and Glutamate after Selective Blockade of D1 and D2 Dopamine Receptors in Freely Moving Rats

Although striatal neurons receive continuous dopamine (DA) input, little information is available on the role of such input in regulating normal striatal functions. To clarify this issue, we assessed how systemic administration of selective D1 and D2 receptor blockers or their combination alters striatal neuronal processing in freely moving rats. Single-unit recording was combined with iontophoresis to monitor basal impulse activity of dorsal and ventral striatal neurons and their responses to glutamate (GLU), a major source of excitatory striatal drive, and DA. SCH-23390 (0.2 mg/kg), a D1 antagonist, strongly elevated basal activity and attenuated neuronal responses to DA compared with control conditions, but GLU-induced excitations were enhanced relative to control as indicated by a reduction in response threshold, an increase in response magnitude, and a more frequent appearance of apparent depolarization inactivation. In contrast, the D2 antagonist eticlopride (0.2 mg/kg) had a weak depressing effect on basal activity and was completely ineffective in blocking the neuronal response to DA. Although eticlopride reduced the magnitude of the GLU response, the response threshold was lower, and depolarization inactivation occurred more often relative to control. The combined administration of these drugs resembled the effects of SCH-23390, but whereas the change in basal activity and the GLU response was weaker, the DA blocking effect was stronger than SCH-23390 alone. Our data support evidence for DA as a modulator of striatal function and suggest that under behaviorally relevant conditions tonically released DA acts mainly via D1 receptors to provide a continuous inhibiting or restraining effect on both basal activity and responsiveness of striatal neurons to GLU-mediated excitatory input.