Period Of Inhibition Research Articles

Identifying the building blocks for learning and memory in the carotid body

Glutamate is a major excitatory neurotransmitter with well-established roles for inducing neural plasticity, learning and memory in the central nervous system. In the carotid body, an organ derived in part from the neural crest, evidence suggests glutamatergic signalling is involved in its sensing of hypoxia. We hypothesized that altered glutamatergic signalling may underpin enhanced chemoreflex responses in carotid body in disease states. Therefore, we have initiated an investigation to assess the presence and location of glutamate receptors expressed in the carotid body of Wistar rats. We mined two independent RNA-sequencing (RNAseq) datasets to identify glutamate signalling components. Digital droplet PCR (ddPCR) was performed to validate the expression of selected glutamatergic target genes. Protein localisation was detailed using immunofluorescence and confocal microscopy in 12–16-week-old normotensive male Wistar rats. Neuronal phenotypes were identified using tyrosine hydroxylase (type I or glomus cells) and glial fibrillary acidic protein antibodies (type II cells). In carotid body extracts, RNAseq data revealed the presence of novel glutamatergic signalling components, not previously described. ddPCR analysis confirmed the expression of AMPA, NMDA and excitatory amino acid transporters. Glutamate ionotropic receptor AMPA type subunit 1 ( Gria1) showed co-localisation with the membrane of type I glomus cells. Glutamate ionotropic receptor NMDA type 1 ( Grin1) showed co-localisation with the nuclei membrane [JP1] of glomus cells. NMDA receptor type subunit 2C ( GRIN2C) showed co-localisation with the membranes of both glomus cells and type II cells. Expression of these receptors was not found on all glomus cells within a cluster suggesting functional heterogeneity within the carotid body. Synaptic Ras GTPase-activating protein 1 ( Syngap), a protein that interacts with glutamate synapses involved in learning, was expressed in both plasma and nuclear membranes of glomus cells. The excitatory amino acid transporter 5 ( EAAT5) showed co-localisation with both type I and type II cells. Additionally, we have observed that a local arterial injection of glutamate (via the internal carotid artery) evoked excitatory activity, followed by an inhibitory period as recorded from the carotid sinus nerve. Our results identified expression and location of glutamatergic AMPA and NMDA receptors in the carotid body[JP2]. We also found the presence of excitatory amino acid transporters, and proteins involved in chaperoning glutamate receptors for learning and memory, All told, we have identified the substrate for glutamate as a transmitter in the carotid body. Whether it plays a role in the learning and memory of carotid body function and/or sensitisation in disease remains to be elucidated. Funding: Health Research Council of New Zealand. Nothing to disclose. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Alteration of myoepithelial cells during botulinum toxin typeA-inhibited salivary secretion.

Intraglandular injection of botulinum toxin type A (BoNT/A) effectively treats sialorrhea. Myoepithelial cells (MECs) are essential for salivary secretion. The role of MECs in BoNT/A-inhibited salivary secretion, and its underlying mechanisms remain unknown. BoNT/A was injected into rat submandibular glands (SMGs). At 1, 2, 4, 8, and 12 weeks postinjection, salivary flow rate of SMGs was measured. Electron microscopy, immunohistochemistry, immunofluorescence, and Western blot analysis were used to detect morphological and functional changes in MECs and chemical denervation in SMGs. BoNT/A temporarily decreased salivary secretion in rat SMGs and this inhibitory effect lasted 4 weeks. During the inhibitory period, MECs atrophied and expressed reduced α-smooth muscle actin (α-SMA), vimentin, and phosphorylated myosin light chain 2 (p-MLC2), suggesting that BoNT/A attenuated MEC contractility. Furthermore, BoNT/A cleaved synaptosome-associated protein 25 (SNAP-25) and decreased the expression and activity of acetylcholinesterase (AChE), indicating that BoNT/A-induced chemical parasympathetic denervation of SMGs by cleaving SNAP-25. BoNT/A temporarily caused MEC atrophy and decreased MEC contractility in rat SMGs, which contributed to reversible inhibition of salivary secretion. The underlying mechanisms involved temporary parasympathetic denervation caused by SNAP-25 cleavage. These findings provide new insights into the mechanisms of BoNT/A-inhibited salivary secretion.

Progressive slowing of clonic phase predicts postictal generalized EEG suppression.

Postictal generalized electroencephalography (EEG) suppression (PGES) is a surrogate marker of sudden unexpected death in epilepsy (SUDEP). It is still unclear which ictal phenomena lead to prolonged PGES and increased risk of SUDEP. Semiology features of generalized convulsive seizure (GCS type 1) have been reported as a predictor of prolonged PGES. Progressive slowing of clonic phase (PSCP) has been observed in GCSs, with gradually increasing inhibitory periods interrupting the tonic contractions. We hypothesized that PSCP is associated with prolonged PGES. We analyzed 90 bilateral convulsive seizures in 50 consecutive patients (21 female; age: 11-62 years, median: 31 years) recruited to video-EEG monitoring. Five raters, blinded to all other data, independently assessed the presence of PSCP. PGES and seizure semiology were evaluated independently. We determined inter-rater agreement (IRA) for the presence of PSCP, and we evaluated its association, as well as that of other ictal features, with the occurrence of PGES, prolonged PGES (≥20 s) and very prolonged PGES (≥50 s) using multivariate logistic regression analysis. We found substantial IRA for the presence of PSCP (percent agreement: 80%; beyond-chance agreement coefficient: .655). PSCP was an independent predictor of the occurrence of PGES and prolonged PGES (p< .001). All seizures with very prolonged PGES had PSCP. GCS type 1 was an independent predictor of occurrence of PGES (p= .02) and prolonged PGES (p= .03) but not of very prolonged PGES. Only half of the seizures with very prolonged PGES were GCS type 1. PSCP predicts prolonged PGES, emphasizing the importance of gradually increasing inhibitory phenomena at the end of the seizures. Our findings shed more light on the ictal phenomena leading to increased risk of SUDEP. These phenomena may provide basis for algorithms implemented into wearable devices for identifying GCS with increased risk of SUDEP.

Unblock the Block! Preventing Inhibitory Failure to Maintain Inhibitory Restraint.

Disrupting Epileptiform Activity by Preventing Parvalbumin Interneuron Depolarization Block Călin A, Ilie AS, Akerman CJ. J Neurosci. 2021;41(45):9452-9465. doi:10.1523/JNEUROSCI.1002-20.2021. Epub 2021 Oct 5.Inhibitory synaptic mechanisms oppose epileptic network activity in the brain. The breakdown in this inhibitory restraint and propagation of seizure activity has been linked to the overwhelming of feedforward inhibition, which is provided in large part by parvalbumin-expressing (PV) interneurons in the cortex. The underlying cellular processes therefore represent potential targets for understanding and preventing the propagation of seizure activity. Here we use an optogenetic strategy to test the hypothesis that depolarization block in PV interneurons is a significant factor during the loss of inhibitory restraint. Depolarization block results from the inactivation of voltage-gated sodium channels and leads to impaired action potential firing. We used focal NMDA stimulation to elicit reproducible epileptiform discharges in hippocampal organotypic brain slices from male and female mice and combined this with targeted recordings from defined neuronal populations. Simultaneous patch-clamp recordings from PV interneurons and pyramidal neurons revealed epileptiform activity that was associated with an overwhelming of inhibitory synaptic mechanisms and the emergence of a partial, and then complete, depolarization block in PV interneurons. To counteract this depolarization block, we developed protocols for eliciting pulsed membrane hyperpolarization via the inhibitory opsin, archaerhodopsin. This optical approach was effective in counteracting cumulative inactivation of voltage-gated channels, maintaining PV interneuron action potential firing properties during the inhibitory restraint period, and reducing the probability of initiating epileptiform activity. These experiments support the idea that depolarization block is a point of weakness in feedforward inhibitory synaptic mechanisms and represents a target for preventing the initiation and spread of seizure activity.

Intracellular and extracellular protective mechanisms of the anammox consortia against exogenous sulfadimidine

Antibiotics and antibiotic resistance genes (ARGs) have been recognized as emerging high-risk pollutants for human and animal health. This study systematically investigated the comprehensive effects of a typical antibiotic (sulfadimidine, SDM) in livestock and poultry breeding wastewater on the anammox process, with the aim of elucidating the intracellular and extracellular protective mechanisms of the anammox consortia to the antibiotic stress. Results revealed that the high-concentration SDM significantly reduced the specific anammox activity (SAA) by 37.8%. Changes in the abundance of Candidatus Kuenenia showed a similar trend with that of SAA, while other nitrogen-related microorganisms (e.g., Nitrosomonas and Nitrospira) contributed to the nitrogen removal especially during the inhibitory period. Resistance of the anammox consortia to SDM mainly depended on the protection of ARGs and EPS. Network analysis revealed the host range of eARGs was relatively larger than that of iARGs, and intI1 was closely associated with representative denitrifiers. In addition, metaproteomic analysis and molecular docking results indicated that abundant proteins in EPS could detain SDM in the extracellular matrix through forming complex via hydrogen bond. These findings provide a guidance for the stable operation of anammox process and ARGs transfer controlling.

Sports Augmented Cognitive Benefits: An fMRI Study of Executive Function with Go/NoGo Task.

Exercise is believed to have significant cognitive benefits. Although an array of experimental paradigms have been employed to test the cognitive effects on exercising individuals, the mechanism as to how exercise induces cognitive benefits in the brain remains unclear. This study explores the effect of dynamic neural network processing with the classic Go/NoGo task with regular exercisers. We used functional magnetic resonance imaging to analyze the brain activation of areas involved in executive function, especially inhibitory control. Nineteen regular joggers and twenty-one subjects as a control group performed the task, and their brain imaging data were analyzed. The results showed that at the attentive visual period, the frontal and parietal areas, including the prefrontal cortex, putamen, thalamus, lingual, fusiform, and caudate, were significantly enhanced in positive activities than the control group. On the other hand, in the following inhibitory control processing period, almost the same areas of the brains of the exercise group have shown stronger negative activation in comparison to the control group. Such dynamic temporal response patterns indicate that sports augment cognitive benefits; i.e., regular jogging increases the brain's visual attention and inhibitory control capacities.

Disrupting Epileptiform Activity by Preventing Parvalbumin Interneuron Depolarization Block

Inhibitory synaptic mechanisms oppose epileptic network activity in the brain. The breakdown in this inhibitory restraint and propagation of seizure activity has been linked to the overwhelming of feedforward inhibition, which is provided in large part by parvalbumin-expressing (PV) interneurons in the cortex. The underlying cellular processes therefore represent potential targets for understanding and preventing the propagation of seizure activity. Here we use an optogenetic strategy to test the hypothesis that depolarization block in PV interneurons is a significant factor during the loss of inhibitory restraint. Depolarization block results from the inactivation of voltage-gated sodium channels and leads to impaired action potential firing. We used focal NMDA stimulation to elicit reproducible epileptiform discharges in hippocampal organotypic brain slices from male and female mice and combined this with targeted recordings from defined neuronal populations. Simultaneous patch-clamp recordings from PV interneurons and pyramidal neurons revealed epileptiform activity that was associated with an overwhelming of inhibitory synaptic mechanisms and the emergence of a partial, and then complete, depolarization block in PV interneurons. To counteract this depolarization block, we developed protocols for eliciting pulsed membrane hyperpolarization via the inhibitory opsin, archaerhodopsin. This optical approach was effective in counteracting cumulative inactivation of voltage-gated channels, maintaining PV interneuron action potential firing properties during the inhibitory restraint period, and reducing the probability of initiating epileptiform activity. These experiments support the idea that depolarization block is a point of weakness in feedforward inhibitory synaptic mechanisms and represents a target for preventing the initiation and spread of seizure activity.SIGNIFICANCE STATEMENT GABAA receptor-mediated synaptic transmission opposes seizure activity by establishing an inhibitory restraint against spreading excitation. Parvalbumin-expressing (PV) interneurons contribute significantly to this inhibitory restraint, but it has been suggested that these cells are overwhelmed as they enter a state of "depolarization block." Here we test the importance of this process by devising an optogenetic strategy to selectively relieve depolarization block in PV interneurons. By inducing brief membrane hyperpolarization, we show that it is possible to reduce depolarization block in PV interneurons, maintain their action potential firing in the face of strong excitation, and disrupt epileptiform activity in an in vitro model. This represents a proof of principle that targeting rate-limiting processes can strengthen the inhibitory restraint of epileptiform activity.

Human corticospinal-motoneuronal output is reduced with 5-HT2 receptor antagonism.

Animal models indicate that serotonin (5-HT) release onto motoneurons facilitates motor output, particularly during strong motor activities. However, evidence for 5-HT effects during human movement are limited. This study examined how antagonism of the 5-HT2 receptor, which is a 5-HT receptor that promotes motoneuron excitability, affects human movement. Ten healthy participants (24.2 ± 1.9 yr) ingested 8 mg of cyproheptadine (competitive 5-HT2 antagonist) in a double-blinded, placebo-controlled, repeated-measures design. Transcranial magnetic stimulation (TMS) of the motor cortex was used to elicit motor evoked potentials (MEPs) from biceps brachii. First, stimulus-response curves (90%-160% active motor threshold) were obtained during very weak elbow flexions (10% of maximal). Second, to determine if 5-HT effects are scaled to the intensity of muscle contraction, TMS at a fixed intensity was applied during elbow flexions of 20%, 40%, 60%, 80%, and 100% of maximal. Cyproheptadine reduced the size of MEPs across the stimulus-response curves (P = 0.045). Notably, MEP amplitude was 22.3% smaller for the cyproheptadine condition for the strongest TMS intensity. In addition, cyproheptadine reduced maximal torque (P = 0.045), lengthened the biceps silent period during maximal elbow flexions (P = 0.037), and reduced superimposed twitch amplitude during moderate-intensity elbow flexions (P = 0.035). This study presents novel evidence that 5-HT2 receptors influence corticospinal-motoneuronal output, which was particularly evident when a large number of descending inputs to motoneurons were active. Although it is likely that antagonism of 5-HT2 receptors reduces motoneuron gain to ionotropic inputs, supraspinal mechanisms may have also contributed to the study findings.NEW & NOTEWORTHY Voluntary contractions and responses to magnetic stimulation of the motor cortex are dependent on serotonin activity in the central nervous system. 5-HT2 antagonism decreased evoked potential size to high-intensity stimulation, and reduced torque and lengthened inhibitory silent periods during maximal contractions. We provide novel evidence that 5-HT2 receptors are involved in muscle activation, where 5-HT effects are strongest when a large number of descending inputs activate motoneurons.

Modulation of the excitatory phase following the cutaneous silent period by vibration.

The post-inhibition excitatory phase (E3) of the cutaneous silent period (CSP) is attributed to the resynchronization of motoneuron activity following the inhibitory period but there is also evidence that a somatosensory startle reflex may contribute to this phase. We hypothesized that the startle reflex component contained in E3 will decrease during vibration. Sixteen healthy individuals were included in the study. CSP was recorded from slightly contracted right thenar muscles after painful index finger stimulation, before, during, and immediately after vibration. The values of the percentage change of E3 relative to pre-stimulus baseline (E3%) were compared before, during, and after vibration for each individual. There was a reduction in E3% during vibration and the values returned to normal immediately after vibration (153.1 ± 43.5%, 115.2 ± 30.2%, 154.9 ± 68.2%, respectively; p = 0.030). E3 is reduced during vibration in healthy individuals, presumably due to suppression of a reflex component, which is superimposed upon the known resynchronization of motoneurons.

Transcranial magnetic stimulation induced early silent period and rebound activity re-examined.

Despite being widely studied, the underlying mechanisms of transcranial magnetic brain stimulation (TMS) induced motor evoked potential (MEP), early cortical silent period (CSP) and rebound activity are not fully understood. Our aim is to better characterize these phenomena by combining various analysis tools on firing motor units. Responses of 29 tibialis anterior (TA) and 8 abductor pollicis brevis (APB) motor units to TMS pulses were studied using discharge rate and probability-based tools to illustrate the profile of the synaptic potentials as they develop on motoneurons in 24 healthy volunteers. According to probability-based methods, TMS pulse produces a short-latency MEP which is immediately followed by CSP that terminates at rebound activity. Discharge rate analysis, however, revealed not three, but just two events with distinct time courses; a long-lasting excitatory period (71.2 ± 9.0 ms for TA and 42.1 ± 11.2 ms for APB) and a long-latency inhibitory period with duration of 57.9 ± 9.5 ms for TA and 67.3 ± 13.8 ms for APB. We propose that part of the CSP may relate to the falling phase of net excitatory postsynaptic potential induced by TMS. Rebound activity, on the other hand, may represent tendon organ inhibition induced by MEP activated soleus contraction and/or long-latency intracortical inhibition. Due to generation of field potentials when high intensity TMS is used, this study is limited to investigate the events evoked by low intensity TMS only and does not provide information about later parts of much longer CSPs induced by high intensity TMS. Adding discharge rate analysis contributes to obtain a more accurate picture about the characteristics of TMS-induced events. These results have implications for interpreting motor responses following TMS for diagnosis and overseeing recovery from various neurological conditions.

Dorsolateral prefrontal cortex hyperactivity during inhibitory control in children with ADHD in the antisaccade task.

Children with ADHD show significant deficits in response inhibition. A leading hypothesis suggests prefrontal hypoactivation as a possible cause, though, there is conflicting evidence. We tested the hypoactivation hypothesis by analyzing the response inhibition process within the oculomotor system. Twenty-two children diagnosed with ADHD and twenty control (CTRL) children performed the antisaccade task while undergoing an fMRI study with concurrent eye tracking. This task included a preparatory stage that cued a prosaccade (toward a stimuli) or an antisaccade (away from a stimuli) without an actual presentation of a peripheral target. This allowed testing inhibitory control without the confounding activation from an actual response. The ADHD group showed longer reaction times and more antisaccade direction errors. While both groups showed activations in saccade network areas, the ADHD showed significant hyperactivation in the dorsolateral prefrontal cortex during the preparatory stage. No other areas in the saccade network had significant activation differences between groups. Further ADHD group analysis OFF and ON stimulant medication did not show drug-related activation differences. However, they showed a significant correlation between the difference in OFF/ON preparatory activation in the precuneus, and a decrease in the number of antisaccade errors. These results do not support the hypoactivity hypothesis as an inhibitory control deficit general explanation, but instead suggest less efficiency during the inhibitory period of the antisaccade task in children. Our findings contrast with previous results in ADHD adults showing decreased preparatory antisaccade activity, suggesting a significant age-dependent maturation effect associated to the inhibitory response in the oculomotor system.

Deciphering the microbial and genetic responses of anammox biogranules to the single and joint stress of zinc and tetracycline

The feasibility of using anaerobic ammonium oxidation (anammox) process to treat wastewaters containing antibiotics and heavy metals was evaluated in this study. The nitrogen removal performance and characteristic parameters were monitored during the whole experimental period of 258 d. The single and joint effects of zinc and tetracycline on the microbial community were studied in upflow anaerobic sludge blanket (UASB) reactors. The anammox performance remained at levels comparable with the initial state at the lower inhibitor concentrations (zinc, 0–2.26 mg L−1; tetracycline, 0–0.5 mg L−1). When the concentrations of zinc and tetracycline increased to 3.39 mg L−1 in R1 and 1.0 mg L−1 in R2, an obvious deterioration in performance was observed. Dual inhibitors with a total concentration of ≥3 mg L−1 caused dramatic decreases in the nitrogen removal efficiency of R3. The quantification results showed that the abundances of eight antibiotic resistance genes (ARGs), czcA and intI1 in the experimental reactors generally increased under stress from metals or/and antibiotics, with final values higher than in the control, while the functional gene abundances were lower. Moreover, most genes exhibited significant correlations. Microbial community analysis indicated that Planctomycetes (represented by Candidatus Kuenenia) was inhibited by both zinc and tetracycline, but still held the dominant position. Furthermore, Caldilinea (belonging to Chloroflexi) maintained a higher abundance during the inhibitory period, implying its potential resistance to both inhibitors. These findings suggested that anammox could be inhibited by metals and antibiotics, but it has the potential to remove nitrogen from wastewaters containing both of them within the concentration threshold.

Investigating the transient and persistent effects of heat on Clostridium difficile spores.

Purpose. Clostridium difficile spores are extremely resilient to high temperatures. Sublethal temperatures are associated with the 'reactivation' of dormant spores, and are utilized to maximize C. difficile spore recovery. Spore eradication is of vital importance to the food industry. The current study seeks to elucidate the transient and persisting effects of heating C. difficile spores at various temperatures.Methods. Spores of five C. difficile strains of different ribotypes (001, 015, 020, 027 and 078) were heated at 50, 60 and 70-80 °C for 60 min in phosphate-buffered saline (PBS) and enumerated at 0, 15, 30, 45 and 60 min. GInaFiT was used to model the kinetics of spore inactivation. In subsequent experiments, spores were transferred to enriched brain heart infusion (BHI) broths after 10 min of 80 °C heat treatment in PBS; samples were enumerated at 90 min and 24 h.Results. The spores of all strains demonstrated log-linear inactivation with tailing when heated for 60 min at 80 °C [(x̄=7.54±0.04 log10 vs 4.72±0.09 log10 colony-forming units (c.f.u.) ml- 1; P<0.001]. At 70 °C, all strains except 078 exhibited substantial decline in recovery over 60 min. Interestingly, 50 °C heat treatment had an inhibitory effect on 078 spore recovery at 0 vs 60 min (7.61±0.06 log10 c.f.u. ml- 1 vs 6.13±0.05 log10 c.f.u. ml- 1; P<0.001). Heating at 70/80 °C inhibited the initial germination and outgrowth of both newly produced and aged spores in enriched broths. This inhibition appeared to be transient; after 24 h vegetative counts were higher in heat-treated vs non-heat-treated spores (x̄=7.65±0.04 log10 c.f.u. ml- 1 vs 6.79±0.06 log10 c.f.u. ml- 1; P<0.001).Conclusions. The 078 spores were more resistant to the inhibitory effects of higher temperatures. Heat initially inhibits spore germination, but the subsequent outgrowth of vegetative populations accelerates after the initial inhibitory period.

A CMOS-based Neuron Circuit for Spiking Neural Networks with Memristive Synapse

The brained-inspired spiking neural networks (SNNs), which can be applied on visual information processing and speech recognition, is attracting great attention especially when combined with emerging electronic synapse (i.e. memristor). The neuron, transmitting and receiving spiking signals, is a vital component to realize the biological rules of SNNs, such as leaky-integrate-and-fire (LIF), inhibitory period, winner takes all (WTA) and bidirectional transmission. In this work, we propose and implement a novel spiking neuron circuit based on complementary- metal-oxide-semiconductor (CMOS) technology. Experimental results show that the neuron circuit can generate spiking pulses, realize lateral inhibition and change the weight of synapse.

In situ detection of neurotransmitters and epileptiform electrophysiology activity in awake mice brains using a nanocomposites modified microelectrode array

A novel nanocomposites modified microelectrode array (MEA) was designed and fabricated for in situ detection of neurotransmitters (glutamate and dopamine) and electrophysiology activity. The MEAs were implanted into the hippocampus of four epileptic mice to detect the neuron activity along with their behaviours. Six spontaneous seizures were recorded, with each seizure having 5 periods. From the normal to the pre-seizure period, both the concentrations of neurotransmitters and the intensities of electrophysiology activities increased by 20%–70%. During the seizure period, the glutamate level dramatically increased to approximately 10 times its normal, while the dopamine level sharply decreased to approximately one third of the normal; the spike firing rate and the power of the local field potential significantly increased more than three-fold. During the inhibitory period, neurotransmitters and electrophysiology activities were significantly inhibited, and then they gradually returned to normal. These results revealed that seizures were highly correlated with glutamate, dopamine and electrophysiology activity and abnormalities in the neuron activity appeared earlier than any abnormal behaviour. Moreover, synchronized changes of these multiple signals in the pre-seizure period could be used to predict seizures. This novel MEA provides an effective technology and a new perspective for understanding the epileptic mechanism.

Effect of high temperature with Litsea cubeba Pers. to control mold growth on bamboo food packaging and its possible modes of action

This study examined the effect of high temperature and Litsea cubeba oil with its main components against molds (Aspergillus niger, Aspergillus flavus, Penicillium sp., Penicillium cyclopium, Rhizopus sp., Fusarium sp., and Cladosporium sp.) on bamboo food packaging. Response surface methodology (RSM) with X1 (concentration of L. cubeba oil at 100, 300, and 500 mg g-1), X2 (temperature at 60, 80, and 100 °C), and X3 (time at 12, 14, and 16 h) was used to find the inhibitory periods of natural mold on packaging plates. The physical properties and the change of chemical components on the bamboo packaging plate before and after temperature treatment were determined to find the mode of action using gas chromatography–mass spectrometry (GC-MS). High temperature (at 100 °C) was a good inhibitor of all mold growth with the MIC (minimum inhibitory concentration) of 300 mg g-1; without heat treatment, no MIC was found. In addition, it was found that by using 300 mg g-1 of L. cubeba oil at 100 °C with an exposure time of 12 h, spore germination on the bamboo surfaces was completely inhibited for at least 290 days. After using high temperature, citral was detected on the surface of the packaging plates. Therefore, these components could be the key factors for inhibiting molds.

Perceptual surprise aides inhibitory motor control.

Neurophysiological studies of cortico-motor excitability have shown that unexpected sounds are followed by motor inhibition. In a recent study, Leiva, Parmentier, Elchlepp, and Verbruggen (2015) derived a prediction from these findings: unexpected, task-irrelevant sounds should increase the ability to withhold motor responses in a Go/NoGo task. Contrary to that prediction, they found that playing unexpected sounds before NoGo-stimuli decreased the likelihood of successful motor inhibition. However, we here argue that the relative timing of unexpected events relative to NoGo-related motor activity is key. Cortico-motor inhibition can be found only until ∼150 ms after the onset of unexpected sounds. Therefore, since Leiva et al. (2015) placed their sounds 200 ms prior to NoGo-stimuli, the inhibitory influence of unexpected sounds may have fully abated before the critical inhibitory period. Consequently, we here repeated their study, with 1 key change: task-irrelevant sounds were presented 50 ms after NoGo-stimulus onset, which ensures that cortico-motor inhibition takes place when motor inhibition is needed. Across 4 experiments, this changed timing produced the results predicted by the previous cortico-motor suppression findings: More responses were successfully withheld after unexpected sounds. These data provide new evidence for the fact that unexpected events can engage an inhibitory control process and benefit motor inhibition. (PsycINFO Database Record

The effects of linalool on the excitability of central neurons of snail Caucasotachea atrolabiata

Linalool is a major constituent of the essential oil of several plant species and possesses several biological activities. In this work, we studied the effects of linalool on excitability of central neurons of land snail Caucasotachea atrolabiata and tried to elucidate the underlying mechanisms. The lower concentration of linalool (0.1mM) showed suppressive action on spontaneous activity and pentylenetetrazole-induced epileptiform activity. These effects were associated with elevation of the action potential threshold and reduction of action potential rising phase, supporting the inhibitory action of linalool on Na+ channels. At this concentration it also prolonged the post stimulus inhibitory period that can take part in its antiepileptic effect and apparently results from increased action potential duration and indirect augmentation of Ca2+-activated K+ currents. At higher concentration, however, linalool (0.4mM) increased the neuronal excitability and induced epileptiform activity. The modulatory effects on action potential waveform during preconvulsive period suggest that the recent effect is mainly dependent on the suppression of outward potassium currents underlying repolarization phase and afterhyperpolarization. The linalool-induced epileptiform activity was abolished by Ca2+ channel blockers, nifedipine and nickel chloride, and selective inhibitor of protein kinase C, chelerythrine, suggesting that Ca2+ inward currents and protein kinase C (PKC) activity are required for linalool-induced epileptiform activity.Our results support the antiepileptic activity of linalool at lower dose, but it shows epileptogenic activity when applied directly on snail neurons at higher dose. Linalool may also be a potential therapeutic agent for activating PKC.

Dual effects of eugenol on the neuronal excitability: An in vitro study

Besides its well-known actions on sensory afferents, eugenol also affects general excitability of the nervous system, but the mechanisms involved in the recent effect, especially through modulation of ion channels, have received much less attention. In this study, we studied the effects of eugenol on the excitability of central neurons of land snail Caucasotachea atrolabiata and tried to elucidate the underlying ionic mechanisms. The lower concentration of eugenol (0.5mM) reversibly reduced the frequency of spontaneous action potentials that was associated with elevation of threshold, reduction of maximum slope of rising phase and prolongation of actin potentials. These effects were mimicked by riluzole, suggesting that they might be mediated by inhibition of Na+ channels. Eugenol also prolonged the single-spike afterhyperpolarization and post stimulus inhibitory period, but these effects seemed to be consequent to action potential prolongation that indirectly augment Ca2+ inward currents and Ca2+-activated K+ currents. This concentration of eugenol was also able to prevent or abolish pentylenetetrazole-induced epileptiform activity. On the other hand, a higher concentration of eugenol (2mM) reversibly increased the frequency of action potentials and then induced epileptiform activity in majority of treated neurons. Several criteria suggest that the inhibition of K+ channels by higher concentration of eugenol and indirect augmentation of Ca2+ currents are central to the hyperexcitability and epileptiform activity induced by eugenol. Our findings indicate that while low concentration of eugenol could have antiepileptic properties, at higher concentration it induces epileptiform activity. It seems that does dependent inhibition of the ionic currents underlying rising and falling phases of action potential is relevant to the eugenol suppressant and excitatory actions, respectively.

Enhanced antifungal activity of michelia oil on the surface of bamboo paper packaging boxes using helium-neon (HeNe) laser and its application to brown rice snack bar

The objective of this research is to evaluate the antifungal activity of michelia oil (Michelia alba) and its main components (linalool and caryophyllene) at concentrations of 300–500 mg g−1against the growth of Aspergillus niger, Aspergillus flavus, Penicillium sp., Rhizopus sp., Fusarium sp. and Cladosporium sp. on the surface of bamboo paper packaging boxes. Next, Helium-Neon (He-Ne) laser operating at 543, 594, 604, 612, and 633 nm for 1 min was used to enhance the antifungal activity of these additives. A spore suspension of each mold (7log10 CFU ml−1) was inoculated on pieces of treated bamboo paper. Visible mycelium growth of all molds on treated bamboo paper compared to control specimens was to calculate minimum inhibitory concentration (MIC). The inhibitory period of michelia oil and linalool in a bamboo paper box with and without laser against natural mold infections on brown rice snack bars was further examined for 8 weeks at 25 °C and 100% RH. The MIC values of michelia oil and linalool with laser treatment were 300 mg g−1 and 150 mg g−1, respectively. Without laser treatment, no MICs were found at the maximum concentration (500 mg g−1). Therefore, linalool was shown to be a stronger inhibitor than the essential oil after laser treatment and should be the key factor in boosting the antifungal activity of michelia oil. In addition, the MICs showed the capability of bamboo paper boxes treated with michelia oil and linalool, with laser treatment to protect against mold growth on snack bars for at least 5–7 weeks in comparison with the control (3 days) during storage at accelerated conditions (25 °C and 100% RH).