European Journal of Neuroscience最新文献

Pain is a morbidity or comorbidity with a high incidence that significantly impacts the well-being of patients. In this study, we evaluated the effects of systemic administration of tramadol, a weak mu-opioid receptor (MOR) agonist, plus quinpirole (a D2-like receptor agonist). The study was performed in naïve rats and in rats with induced inflammatory and neuropathic pain. To measure the antinociceptive effect of the drugs, thermonociceptive and mechanonociceptive stimuli were applied and the emotional aspects of pain were evaluated using conditional place preference (CPP) experiments.

Systemic quinpirole produced an antinociceptive effect only in naïve male rats. In naïve female animals, a small but significant pronociceptive effect was observed following quinpirole application. Tramadol plus quinpirole in male animals reversed allodynia and hyperalgesia induced by inflammatory and neuropathic insults, which were not alleviated by either drug alone. CPP experiments revealed that systemic quinpirole plus tramadol treatment was effective only in an inflammatory pain model. To evaluate whether tolerance to the antinociceptive effect was prevented by the combination of the drugs, a repeated administration five-day trial of tramadol plus quinpirole was evaluated under inflammatory pain conditions; quinpirole only slightly prevented the antinociceptive tolerance of MOR agonists.

D2-like agonists are effective adjuvants for treating painful conditions in combination with a low dose of MOR agonists. Our results could lead to an investigation of whether these dopaminergic drugs in combination with opioids might reduce the MOR agonist dose while obtaining a higher analgesic effect with fewer side effects in humans.

Interception, essential for activities like driving and sports, can be characterized by varying degrees of predictive behaviour. We developed a visually guided task to explore how target predictability and visibility influenced interception actions. The task featured a falling dot influenced by horizontal velocity, gravity and air friction, with predictability manipulated through external forces that altered the target's trajectory. We also introduced spatial occlusion to limit visual information. Our results show that low target variability favoured predictive behaviours, while high variability led to more reactive responses relying on online feedback. Manual responses displayed increased variability with changes in target motion, whereas eye trajectories maintained constant curvature across conditions. Additionally, higher target variability delayed the onset of hand movements but did not affect eye movement onset, making gaze position a poor predictor of hand position. This distinction highlights the different adaptive patterns in hand and eye movements in response to target trajectory changes. Participants maintained stable interception behaviours within and across sessions, indicating individual preferences for either predictive or more reactive actions. Our findings reveal a dynamic interplay between target predictability and interception, illustrating how humans combine predictive and reactive behaviours to manage external variability.

Brain astrocyte glycogenolysis is regulated in part by the second messenger adenosine 3′5′-cyclic monophosphate (cAMP). Hypothalamic astrocyte glycogen metabolism shapes glucose counterregulation, under the control of glucose transporter-2 (GLUT2), a plasma membrane glucose carrier and sensor. Hypothalamic astrocyte cAMP is subject to neurotransmitter control, but effects of nutrient cues on this messenger are unclear. Here, an established hypothalamic primary astrocyte culture model and gene knockdown tools were used to investigate the premise that GLUT2 exerts sex-dimorphic regulation of cAMP-protein kinase A (PKA) signalling in these glia. Data show that basal cAMP was elevated in female versus male; GLUT2 gene silencing up-regulated or down-regulated this profile in male versus female. Glucoprivation increased cAMP content in astrocytes of each sex, yet GLUT2 siRNA pretreatment exacerbated (male) or blunted (female) this stimulatory effect. PKA and phosphoPKA levels in glucose-supplied astrocytes were increased (male) or decreased (female) by GLUT2 knockdown. PKA protein was amplified, yet phosphoPKA was refractory to glucose withdrawal in male, while females showed sustained PKA expression alongside diminished phosphoPKA. GLUT2 siRNA pretreatment exacerbated glucoprivic augmentation of PKA content in male but down-regulated both PKA and phosphoPKA proteins in female. Evidence for parallel GLUT2 siRNA-associated changes in cAMP and PKA, albeit in opposing directions in the two sexes, infers that GLUT2 control of hypothalamic astrocyte cAMP-dependent PKA signalling is sex-specific. Data also disclose that in the female, GLUT2 curbs the baseline phosphoPKA/PKA expression ratio but is not involved in glucoprivic suppression of this ratio.

An unusually large amplitude spontaneous miniature endplate potentials (gMEPPs) occur naturally at low frequency at the vertebrate neuromuscular junction. Unlike the normal miniature endplate potentials (nMEPPs), these gMEPPs have long duration and long time to peak. More strikingly, gMEPPs seem to be independent of extracellular and intracellular Ca^+2. and have a greater temperature sensitivity than nMEPPs. They are potentiated by tetrodotoxin but inhibited by acetylcholine (ACh) receptor blockers indicating ACh is the neurotransmitter responsible for gMEPPs. The frequency of gMEPPs is greatly increased in muscles weakened by various drugs, toxins or disease conditions suggesting that gMEPPs may be a part of possible neurotrophic mechanism to preserve effective neuromuscular transmission when the normal function is compromised.

Here, I discuss data sharing and re-use as a moral imperative for research that uses animals in neuroscience. I argue that we are ethically required to make sure that we gain as much knowledge as possible from the animals we use, and that doing so involves making sure that the data from our experiment makes it into the public record of knowledge. I suggest several ways in which journals, grant bodies and policymakers can contribute to making data sharing and re-use mainstream practices.

When performing cognitive tasks in noisy conditions, the brain needs to maintain task performance while additionally controlling the processing of task-irrelevant and potentially distracting auditory stimuli. Previous research indicates that a fundamental mechanism by which this control is achieved is the attenuation of task-irrelevant processing, especially in conditions with high task demands. However, it remains unclear whether the processing of complex naturalistic sounds can be modulated as easily as that of simpler ones. To address this issue, the present fMRI study examined whether activity related to task-irrelevant meaningful speech is attenuated similarly as that related to meaningless control sounds (nonsense speech and noise-vocoded, unintelligible sounds). The sounds were presented concurrently with three numerical tasks varying in difficulty: an easy control task requiring no calculation, a ‘routine’ arithmetic calculation task and a more demanding ‘creative’ arithmetic task, where solutions are generated to reach a given answer. Consistent with their differing difficulty, the tasks activated fronto-parieto-temporal regions parametrically (creative > routine > control). In bilateral auditory regions, activity related to the speech stimuli decreased as task demands increased. Importantly, however, the attenuation was more pronounced for meaningful than nonsense speech, demonstrating that distractor type can strongly modulate the extent of the attenuation. This also suggests that semantic processing may be especially susceptible to attenuation under conditions with increased task demands. Finally, as this is the first study to utilize the ‘creative’ arithmetic task, we conducted exploratory analyses to examine its potential in assessing neural processes involved in mathematical problem-solving beyond routine arithmetic.

Achieving successful blinding is a persistent challenge for clinical trials involving transcranial direct current stimulation. Studies involving populations with increased sensory sensitivity, such as children, could be at risk for increased bias from inadequate blinding due to unique sensation of stimulation relative to adults. The objectives of this study were 1) To examine differences in transcranial stimulation blinding between children and young adults and its relationship to sensory sensitivity. 2) To test the efficacy of an ActiSham protocol for participant blinding, compared to a traditional sham protocol. Typically developing right-handed children (N = 12, 5–14 yr) and young adults (N = 15, 15–25 yr) completed a single-session study to test transcranial stimulation blinding after three conditions counterbalanced across participants: Active, Sham and ActiSham. Stimulation was paired with a motor learning task to simulate a combinatory neurorehabilitation intervention. After each condition, participants reported if they received real or fake stimulation and their response confidence. To quantify sensory sensitivity, participants completed the Sensory Profile (second edition). Compared to a chance level, 1) children and young adults correctly identified Active stimulation, 2) children incorrectly identified Sham and ActiSham stimulation and 3) young adults identified Sham and ActiSham stimulation at chance-level. Blinding accuracy was not related to sensory sensitivity. Children report stimulation as real stimulation with higher confidence for almost all conditions, indicating unsuccessful blinding compared to young adults. Future studies should consider alternative sham protocols or methods to improve blinding in child participants.

17β-Estradiol (E2) is a sex hormone that acts on many brain regions to produce changes in neuronal activity and learning. A key brain region sensitive to E2 is the dorsal striatum (also called caudate-putamen), which controls motor behaviour, goal-directed learning and habit learning. In adult rodents, oestrogen receptors (ERs) in the dorsal striatum are localized to the plasma membrane and include ERα, ERβ and G protein-coupled ER (GPER). E2, either naturally produced or exogenously applied, may influence neuronal excitability, basal synaptic transmission and long-term synaptic potentiation. These effects may be due to direct action on signalling pathways or may be due to changes in dopamine availability. In particular, estradiol influences dopamine release, dopamine receptor expression and dopamine transporter expression. We review the cellular effects that E2 has in the dorsal striatum, distinguishing between exogenously applied E2 and the oestrous cycle, as well as its influence on dorsal striatal-dependent motor and learning behaviour.

The aim of the present study was to determine if anodal transcutaneous spinal direct current stimulation (tsDCS) affects corticospinal excitability (CSE) and voluntary activation (VA) of the quadriceps femoris muscle (QM). This was a double-blind, randomized study in which spine-shoulder anodal tsDCS (active electrode centered over T11–12, 2.5 mA, 20 min) was applied in a seated position. Transcranial magnetic stimulation (TMS) was used to measure motor evoked potentials (MEP) and construct stimulus–response curves in healthy participants (eight females and five males, Experiment 1). VA was measured via the interpolated twitch technique, whereby muscle twitches were evoked using electrical femoral nerve stimulation and TMS (seven females and six males, Experiment 2). Measurements were carried out before, directly, and 30 min after sham and anodal tsDCS (with ≥4 days between sessions). There was no interaction between stimulation × time on stimulus–response curve expressed by slope, stimulus intensity corresponding to 50% of the maximal MEP, and peak-to-peak amplitude of the maximal MEP. Maximal voluntary isometric contraction (MVIC) torque did not change and VA was not affected regardless of the QM torque level (25, 50, or 100% of MVIC). A single, twenty-minute session of spine-shoulder anodal tsDCS did not increase CSE and VA of QM during submaximal and maximal contraction. This suggests that neither excitability to a known input nor responsiveness of motoneurons to submaximal and maximal cortical drive were affected by anodal tsDCS.