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The Inhibitory effect of electrical low-frequency stimulation (LFS) on neuronal excitability and seizure occurrence has been indicated in experimental models, but the precise mechanism has not established. This investigation was intended to figure out the role of α 1 and α 2 adrenergic receptors in LFS' inhibitory effect on neuronal excitability. Epileptiform activity induced in an in vitro rat hippocampal slice preparation by high K + ACSF and LFS (900 square wave pulses at 1 Hz) was administered at the beginning of epileptiform activity to the Schaffer collaterals. In CA1 pyramidal neurons, the electrophysiological properties were measured at the baseline, before high K + ACSF washout, and at 15 min after high K + ACSF washout using whole-cell, patch-clamp recording. Results indicated that after high K + ACSF washout, prazosine (10 µM; α 1 adrenergic receptor antagonist) and yohimbine (5 µM; α 2 adrenergic receptor antagonist) suppressed the LFS' effect of reducing rheobase current and utilization time following depolarizing ramp current, the latency to the first spike following a depolarizing current and latency to the first rebound action potential following hyperpolarizing current pulses. Thus, it may be proposed that LFS' inhibitory action on the neuronal hyperexcitability, in some way, is mediated by α 1 and α 2 adrenergic receptors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI) is associated with epileptiform activity in the hippocampus; however, the underlying mechanisms have not been fully determined. The goal was to understand what changes take place in intrinsic neuronal physiology in the hippocampus after blunt force trauma to the cortex. In this context, hyperpolarization-activated cation current (I h ) currents may have a critical role in modulating the neuronal intrinsic membrane excitability; therefore, its contribution to the TBI-induced hyperexcitability was assessed. In a model of TBI caused by controlled cortical impact (CCI), the intrinsic electrophysiological properties of pyramidal neurons were examined 1 week after TBI induction in rats. Whole-cell patch-clamp recordings were performed under current- and voltage-clamp conditions following ionotropic receptors blockade. Induction of TBI caused changes in the intrinsic excitability of pyramidal neurons, as shown by a significant increase and decrease in firing frequency and in the rheobase current, respectively (p < .05). The evoked firing rate and the action potential time to peak were also significantly increased and decreased, respectively (p < .05). In the TBI group, the amplitude of instantaneous and steady-state I h currents was both significantly smaller than those in the control group (p < .05). The I h current density was also significantly decreased (p < .001). Findings indicated that TBI led to an increase in the intrinsic excitability in CA1 pyramidal neurons and changes in I h current could be, in part, one of the underlying mechanisms involved in this hyperexcitability., (© 2020 Wiley Periodicals LLC.)

Introduction: Cisplatin is one of the most commonly used antineoplastic drugs; nonetheless, its ototoxic dose-limiting side effects have remained a significant challenge in clinical practice. The recognition of the exact template of hearing loss induced by multiple low doses of cisplatin could be of great help in managing the treatment process. The present study aimed to investigate the effects of multiple doses of this drug on the auditory system., Material and Methods: The present study was performed using an experimental guinea pig model in four groups as follows:1- 0.9% sodium chloride solution, 2- total dose of 7.5 mg/kg Cisplatin, 3- total dose of 10 mg/kg Cisplatin, and 4- total dose of 12.5 mg/kg cisplatin. The drugs were injected as 2.5 mg/kg/daily IP access in all groups. The auditory brainstem response (ABR) test was performed before the treatment and after every injection on a daily basis up to 72 h after the last injection., Results: There was dose-dependent significant hearing loss in all evaluated frequencies in three cisplatin groups. The general template of induced hearing loss during experimental days was almost the same in groups Cis7.5 and Cis10. In Cis 12.5 group, there was a jump in the threshold shift on the 5th day of the experiment and an upward trend in the function., Conclusion: As evidenced by the obtained results, the monitoring of hearing loss after every injection in patients who receive the drug and detecting the exact dose-dependent pattern of the induced hearing loss is of great help in controlling its undesirable destructive side effects on the auditory system.

Low frequency stimulation (LFS) has anticonvulsant effect and may restore the ability of long-term potentiation (LTP) to the epileptic brain. The mechanisms of LFS have not been completely determined. Here, we showed that LTP induction was impaired following in vitro epileptiform activity (EA) in hippocampal slices, but application of LFS prevented this impairment. Then, we investigated the involvement of α-adrenergic receptors in this effect of LFS. EA was induced by increasing the extracellular K + concentration to 12 mM and EPSPs were recorded from CA1 neurons in whole cell configuration. EA increased EPSP amplitude from 6.9 ± 0.7 mV to 9.6 ± 0.6 mV. For LTP induction, the Schaffer collaterals were stimulated by high frequency stimulation (HFS; two trains of 100 pulses, 100 Hz at the interval of 20 s). The application of HFS resulted in 40.9 ± 2.3% increase in the amplitude of EPSPs. However, following EA, HFS could not produce any significant changes in EPSP amplitude. Administration of LFS (1 Hz, 900 pulses) to Schaffer collaterals at the beginning of EA restored LTP induction to the hippocampal slices and HFS increased the EPSPs amplitude up to 41.7 ± 3.1% of baseline. When slices were perfused by prazosin (α 1 -adrenergic receptor antagonist; 10 μM) before and during LFS application, LFS improvement on LTP induction was reduced significantly. Perfusion of slices by yohimbine (α 2 -adrenergic receptor antagonist; 5 μM) had no effect on LFS action. Therefore, it may be concluded that following epileptiform activity, LFS can improve the impairment of LTP generation through α 1 , but not α 2 , adrenergic receptor activity., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Low-frequency stimulation has demonstrated promising seizure suppression in animal models of epilepsy, while the mechanism of the effect is still debated. Changes in intrinsic properties have been recognized as a prominent pathophysiologically relevant feature of numerous neurological disorders including epilepsy. Here, it was evaluated whether LFS can preserve the intrinsic neuronal electrophysiological properties in a rat model of epilepsy, focusing on the possible involvement of voltage-gated Ca 2+ channels. The amygdala kindling model was induced by 3 s monophasic square wave pulses (50 Hz, 1 ms duration, 12times/day at 5 min intervals). Both LFS alone and kindled plus LFS (KLFS) groups received four packages of LFS (each consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz with the after discharge threshold intensity), which in KLFS rats was applied immediately after kindling induction. Whole-cell patch-clamp recordings were made in the presence of fast synaptic blockers 24 h after the last kindling stimulations or following kindling stimulations plus LFS application. In the KLFS group, both the rebound excitation and kindling-induced intrinsic hyperexcitability were decreased, associated with a regular intrinsic firing as indicated by a lower coefficient of variation. The amplitude of afterdepolarization (ADP) and its area under the curve were both decreased in the KLFS group compared to the kindled group. LFS prevented the increasing effect of kindling on Ca 2+ currents in the KLFS group. Findings provided evidence for a novel form of epileptiform activity suppression by LFS in the presence of synaptic blockade possibly by decreasing Ca 2+ currents., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Autism spectrum disorder (ASD) is a common neuropsychiatric disorder, which is characterized by impairment in social interaction and cognitive behaviors. However, there is not much electrophysiological data available on alterations of neuronal excitability in autism. Here, we assessed the pattern of neuronal excitability and the possible contribution of Ih current to the altered excitability of hippocampal CA1 pyramidal neurons in a rat model of VPA-induced ASD-like behavior. Pregnant Wistar rats received valproic acid (VPA, 500 mg/kg) at gestational day 12.5. All offspring were subjected to behavioral tests to verify the induction of ASD-like behaviors. On postnatal day (PND) 45, whole-cell patch-clamp recordings were performed on hippocampal CA1 pyramidal neurons in slices obtained from control and prenatal VPA-exposed pups, under current and voltage-clamp conditions. Our results showed that beside the induction of behavioral abnormalities in ASD pups, higher excitability of hippocampal CA1 pyramidal neurons was also prominent, as evidenced by a significant increase in the spontaneous firing frequency and evoked firing rate, as well as a significant decrease in the rheobase current. In the VPA-exposed group, the steady-state (ISS) Ih current amplitude was significantly smaller than control cells. The Ih half-activation voltage shifted toward more negative potentials in the VPA-exposed group. The sag ratio was also significantly less than the control cells. Moreover, the cell soma size was shifted toward smaller diameter in VPA-exposed group. Overall, induction of ASD-like behaviors was associated with neuronal hyperexcitability, which, at least in part, could be attributed to the changes in Ih channels function., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: It is a long time that natural toxin research is conducted to unlock the medical potential of toxins. Although venoms-toxins cause pathophysiological conditions, they may be effective to treat several diseases. Since toxins including scorpion toxins target voltage-gated ion channels, they may have profound effects on excitable cells. Therefore, elucidating the cellular and electrophysiological impacts of toxins, particularly scorpion toxins would be helpful in future drug development opportunities., Methods: Intracellular recording was made from F1 cells of Helix aspersa in the presence of calcium Ringer solution in which Na + and K + channels were blocked. Then, the modulation of channel function in the presence of extracellular application of F4 and F6 toxins and kaliotoxin (KTX; 50 nM and 1 μM) was examined by assessing the electrophysiological characteristics of calcium spikes., Results: The two active toxin fractions, similar to KTX, a known Ca 2+ -activated K + channel blocker, reduced the amplitude of AHP, enhanced the firing frequency of calcium spikes and broadened the duration of Ca 2+ spikes. Therefore, it might be inferred that these two new fractions induce neuronal hyperexcitability possibly, in part, by blocking calcium-activated potassium channel current. However, this supposition requires further investigation using voltage clamping technique., Conclusion: These toxin fractions may act as blocker of calcium-activated potassium channels., Competing Interests: Conflict of interest The authors declare no conflict of interest.

Investigation of the role of the local field potential (LFP) fluctuations in encoding the received sensory information by the nervous system remains largely unknown. On the other hand, transmission of these translation rules in information transmission between the structure of sensory stimuli and the cortical oscillations to the bio-inspired artificial neural networks operating at the efficiency of the nervous system is still a vague puzzle. In order to move towards this important goal, computational neuroscience tools can be useful so, we simulated a large-scale network of excitatory and inhibitory spiking neurons with synaptic connections consisting of AMPA and GABA currents as a model of cortical populations. Spiking network was equipped with spike-based unsupervised weight optimization based on the dynamical behavior of the excitatory (AMPA) and inhibitory (GABA) synapses using Spike Timing Dependent Plasticity (STDP) on the MNIST benchmark and we specified how the generated LFP by the network contained information about input patterns. The main result of this article is that the calculated coefficients of Prolate spheroidal wave functions (PSWF) from the input pattern with mean square error (MSE) criterion and power spectrum of LFP with maximum correntropy criterion (MCC) are equal. The more important result is that 82.3% of PSWF coefficients are the same as the connecting weights of the cortical neurons to the classifying neurons after the completion of the training process. Higher compliance percentage of coefficients with synaptic weights (82.3%) gives the expectance us that this coding rule will be able to extend to biological systems. Eventually, we introduced the cortical spiking network as an information channel, which transmits the information of the input pattern in the form of PSWF coefficients to the power spectrum of the output generated LFP., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Traumatic brain injury (TBI), as an expanding public health epidemic, is a common cause of death among youth. TBI is associated with cognitive deficits and memory impairment. Hydrogen sulfide (H 2 S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. In the present study the potential neuroprotective role of sodium hydrosulfide (NaHS), an H 2 S donor on TBI induced memory deficit in a rat model of controlled cortical impact (CCI) injury was investigated. CCI model was used to induce TBI. Male rats were randomly assigned into the following groups: control, sham, sham treated with NaHS, TBI, and TBI treated with NaHS (3 and 5mg/kg). NaHS was injected intraperitoneally 5min before TBI induction. Learning and memory were assessed using Morris water maze (MWM) on days 8-12 following injury. CCI resulted in MWM deficits. Injured animals showed a slower rate of acquisition with respect to the sham-operated animals [F (1, 24)=13.97, P<0.01, two-way ANOVA]. NaHS improved spatial memory impairment of injured rats. Treatment with NaHS (5 mg/kg) decreased the escape latency [F (1, 24)=7.559, P<0.05, two-way ANOVA] and traveled distance [F (1, 12)=6.398, P<0.05, Two way ANOVA)]. In probe test, injured animals spent less time in target zone (P<0.05, unpaired t-test) and NaHS did not have any effect on this parameter (p>0.05, one way ANOVA). These findings suggest that NaHS has a neuroprotective effect on TBI-induced memory impairment in rats., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

Herein the effect of hippocampal orexin type-1 receptors (OX1Rs) blockade on morphine withdrawal syndrome was studied. Animals were made dependent by subcutaneous (s.c.) administration of morphine sulfate (10mg/kg) at an interval of 12h for 9 consecutive days. Thereafter, on day 10, naloxone hydrochloride (1.5mg/kg, i.p.) was injected and the somatic signs of withdrawal syndrome were monitored during a 25-min period. Two groups of animals received bilateral microinjection of either SB-334867, a selective OX1Rs antagonist, (0.5μg/0.5μl), or its vehicle into the dorsal hippocampus immediately before each morphine injection. Other groups of animals were made dependent at first and only received a single microinjection of SB-334867 or vehicle on day 10 before naloxone injection. The results showed that intra-hippocampal microinjection of SB-334867 before each morphine treatment, significantly decreased the signs of morphine withdrawal, including teeth chattering (dependent: 18.5±2.3, SB treated: 5±1, p<0.001), diarrhea (dependent: 8.7±0.6, SB treated: 4.1±0.6, p<0.001), ptosis (dependent: 33.8±3.7, SB treated: 11.6±1.1, p<0.001), and chewing (dependent: 40±2.3, SB treated: 29±2.4, p<0.01). SB-334867 did not attenuate withdrawal syndrome, when it was microinjected as a single dose immediately before naloxone injection. The present results suggest a role for orexin in naloxone-precipitated withdrawal and thus possibly morphine dependence and this effect is, at least in part, via OX1Rs in the dorsal hippocampus., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 Ca 2+ -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., (Copyright © 2016. Published by Elsevier Inc.)

Epilepsy affects about 1-2 % of world population as a chronic neurological disease that is manifested by repeated and consecutive seizures (Grone and Baraban, Nat Neurosci 18(3):339-343, 2015). There is no definitive therapy for epilepsy and antiepileptic drugs cannot offer a permanent and definitive cure for epilepsy, and most epileptic patients become drug resistant (Sasa, J Pharmacol Sci 100(5):487-494, 2006). Surgery and removal of the epileptic focus is a substitute method for treating drug-resistant patients and epilepsy surgery of either side of the brain improves seizure control. Temporal lobectomy is the most common epilepsy surgery and is associated with high success rates. Other studies have reported higher success rates for carefully selected temporal lobe seizure patients. Some physicians still consider temporal lobectomy an extreme procedure, citing the risks of side effects, including loss of memory, visual disturbances, and emotional change, associated with the removal of brain tissue (Spencer, Lancet Neurol 1(6):375-382, 2002; Wiebe et al., N Engl J Med 345(5):311-318, 2001; Yasargil et al., J Neurosurg 112(1):168-185, 2010). Nowadays, direct electrical stimulation (in the form of low- or high-frequency stimulation) in the location involved in seizures is used as a potentially suitable treatment method for this destructive disease in both laboratory animals and humans (Goodman et al., Epilepsia 46(1):1-7, 2005; Richardson et al., Epilepsia 44(6):768-777, 2003; Velasco et al., Epilepsia 41(2):158-169, 2000). Low-frequency stimulation causes less damage to the epileptic area and surrounding neuronal structures compared to high-frequency stimulation, and it can be a suitable option for patients suffering from epilepsy (Goodman et al., Epilepsia 46(1):1-7, 2005). Since the cellular mechanism of this stimulation is not clearly known, the purpose of this review research was to investigate the anticonvulsive effects of low-frequency electrical stimulation and the probable cellular mechanism involved in it.

In this study, the effect of repetitive transcranial magnetic stimulation (rTMS) on the kindling induced changes in electrophysiological firing properties of hippocampal CA1 pyramidal neurons was investigated. Male Wistar rats were kindled by daily electrical stimulation of the basolateral amygdala in a semi-rapid manner (12 stimulations/day) until they achieved stage-5 seizure. One group (kindled+rTMS (KrTMS)) of animals received rTMS (240 pulses at 1 Hz) at 5 min after termination of daily kindling stimulations. Twenty-four hours following the last kindling stimulation electrophysiological properties of hippocampal CA1 pyramidal neurons were investigated using a whole-cell patch clamp technique, under current clamp condition. Amygdala kindling significantly decreased the adaptation index, post-afterhyperpolarization, rheobase current, utilization time, and delay to the first rebound spike. It also caused an increase in the voltage sag, number of rebound spikes and number of evoked action potential. Results of the present study revealed that application of rTMS following kindling stimulations had antiepileptogenic effects. In addition, application of rTMS prevented hyperexcitability of CA1 pyramidal neurons induced by kindling and conserved the normal neuronal firing., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is characterized by the formation of amyloid beta (Aβ) plaques in the brain. Dysfunctional excitatory synaptic transmission and neuronal plasticity are generally accepted as primary events in the development of AD. There is evidence to suggest that both COX-1 expression and COX-2 expression are changed in the brain of AD patients. However, the impact of COX-dependent mechanisms on synaptic dysfunction underlying the memory deficit is not fully elucidated. In the present study effects of non-selective NSAIDs (aspirin and sodium salicylate) on associated memory impairment as well as Aβ-mediated suppression of synaptic plasticity in the hippocampus were examined. Aβ1-42 (5μg/μl) and ibotenic acid (5μg/μl) were injected bilaterally into the dorsal hippocampus of rats and the spatial memory and long term potentiation (LTP) were assessed by water maze performance and in vivo field potential recording, respectively. Field excitatory post synaptic potentials (fEPSP) were recorded from stratum radiatum of area CA1 following Schaffer collateral stimulation. Behavioral study revealed that both sub-chronic high dose of sodium salicylate (SS) and chronic low dose of aspirin improved the spatial memory impairment of Aβ treated rats, however the effects of SS were lower than those of aspirin. Animals treated with SS and aspirin showed a significant decrease in escape latency (SS: F(1, 24)=15.85, p<0.01, aspirin: F(1, 22)=25.24, p<0.001, ANOVA). Furthermore, in probe test, animals treated with aspirin (p<0.05) but not SS (p>0.05) spent more time (one-way ANOVA) in target quadrant zone. Both applied drugs restored the suppression of fEPSP slope LTP that was induced by Aβ treatment (unpaired t-test, p<0.001). Aspirin showed a preventative effect also against Aβ-induced changes in LTP and memory task when applied before Aβ administration. Since aspirin and SS improved synaptic dysfunction, we can suggest that COX-dependent mechanisms may play a role in synaptic dysfunction in an experimental model of AD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) has emerged as a potential therapeutic strategy in the treatment of neurological disorders including epilepsy. However, the cellular mechanism responsible for the effects of DBS remains largely undefined. Therefore, using electrophysiological approach, we aimed to determine the antiepileptic effects and restorative potential of low frequency stimulation (LFS) on amygdala kindling-induced changes in electrophysiological properties of rat hippocampal CA1 pyramidal neurons., Methods: Animals were kindled by electrical stimulation of amygdala in a rapid kindling manner (12 times per day). In one group of animals, immediately after termination of daily 12 rapid kindling stimulations, the kindling site was subjected to 4 packages of LFS at intervals of 5 min (each package contained 200 monophasic square-wave pulses, 0.1 ms pulse duration at 1 Hz). Whole cell patch clamp recording under current clamp conditions was performed on visually identified pyramidal neurons in hippocampal slice preparations obtained from amygdala-kindled rats and the rats receiving LFS., Results: Kindling of the right basolateral amygdala profoundly affected spontaneous firing behavior and repetitive discharge characteristics of pyramidal neuronal electrophysiological properties. Application of LFS at the kindling site almost completely prevented the development of epilepsy and the disruptive effects of kindling on neuronal electrical activity through restoration of the normal electrophysiological characteristics., Conclusions: The results of this study implied that application of LFS during kindling acquisition prevents the kindling induced changes in functional electrical properties of CA1 pyramidal neurons, suggesting that this action may be involved in the antiepileptogenic mechanism of LFS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The main goal of this ex vivo study was to assess and compare the cellular and electrophysiological effects of two dental biomaterials, white mineral trioxide aggregate (WMTA) and calcium enriched mixture (CEM) cement, on neuronal cell excitability and electrical properties., Materials and Methods: A conventional intracellular current clamp technique was used to study the cellular effects of WMTA and CEM on the excitability, firing and the shape of action potential of neuronal soma membrane of F(1) nerve cells. The dental biomaterials were prepared according to the manufacturers' directions and were applied to the bathing media and 0.05 mL of total mixture of each dental material at a distance of 3 mm from the cells., Results: Findings indicated that exposure to both dental biomaterials shifted the irregular high frequency firing type observed in control conditions to a more regular low frequency firing pattern. Neuronal exposure to WMTA, but not CEM, significantly hyperpolarized the cell resting membrane potential. Both treatments significantly influenced the duration and the amplitude of action potentials. Extracellular application of either CEM or WMTA caused a significant increase in the after hyperpolarization (AHP) amplitude and AHP area, but the potentiating effect of WMTA was more effective than CEM., Conclusion: Treatment with WMTA or CEM resulted in a profound alteration in the firing behaviour of F(1) cells and changed the AP characteristics. Both dental biomaterials reduced the neuronal activity possibly through enhancement of K(+) outward current. This may possibly explain the positive mechanisms of these biomaterials in regenerative endodontics, though further research is needed for such a conclusion.

In the present research, we extend a biologically plausible cortical neural population model (CPM), which was developed previously in the literature, by integrating the functional role of astrocytes in the synaptic transmission in the model. In other words, the original CPM is modified to consider neuron-astrocyte interaction. Then, two modified CPMs (MCPMs) are coupled via excitatory synapses; the astrocytes are also coupled through gap junctions. Using the coupled MCPMs (CMCPMs), it is demonstrated that the healthy astrocytes provide appropriate feedback control in regulating neural activity. As a result, the astrocytes compensate the coupling variations between CPMs in order to maintain the normal level of synchronized behavior. Next, malfunction of astrocytes in the regulatory feedback loop as one of the plausible causes of seizures is investigated. In this way, dysfunctional astrocytes are not any more able to regulate the excessive increase of the inter-population coupling strength. Consequently, disruption of the homeostatic function of astrocytes may initiate the hypersynchronous firing of neurons. This suggests that the neuron-astrocyte interaction may represent a novel target to develop effective therapeutic strategies for epilepsy., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

In the present study, a biologically plausible neuronal population model is developed, which considers functional outcome of neuron-astrocyte interactions. Based on established neurophysiologic findings, astrocytes dynamically regulate the synaptic transmission of neuronal networks. The employed structure is based on the main physiological and anatomical features of the CA1 subfield of the hippocampus. Utilizing our model, we demonstrate that healthy astrocytes provide appropriate feedback control in regulating neural activity. In this way, the astrocytes compensate the increase of excitation coupling strength among neurons and stabilize the normal level of synchronized behavior. Next, malfunction of astrocytes in the regulatory feedback loop is investigated. In this way, pathologic astrocytes are no longer able to regulate and/or compensate the excessive increase of the excitation level. Consequently, disruption of astrocyte signaling initiates hypersynchronous firing of neurons. Our results suggest that diminishing of neuron-astrocyte cross-talk leads to an abnormal synchronized neuronal firing, which suggests that astrocytes could be a proximal target for the treatment of related disorders including epilepsy., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Introduction: Mineral trioxide aggregate (MTA) is an endodontic material with different clinical applications e.g. root-end filling, pulp capping and perforation repair. It has been reported to possess antimicrobial and antifungal activities. The aim of this study was to examine the effect of White MTA on formalin-induced hyperalgesia in a rat with inflammatory pain., Materials and Methods: Inflammatory pain was induced by subcutaneous (SC) injection of formalin (40 µL, 2.5%) into the rat upper lip. The nociceptive behavioral responses i.e. shaking of the lower jaw and face rubbing were quantified. 40 µL of eugenol (50 mg/kg), WMTA (20 mg/0.2 mL) or ketoprofen were injected solely or in combination with formalin 2.5% and the behavioral responses were compared with those observed after formalin treatment alone. One-way ANOVA, Tukey were used for analysis of data., Results: Formalin 2.5% provoked a biphasic nociceptive response, with an early and short lasting first tonic phase followed by a second phase. Solely SC injection of either WMTA or ketoprofen (a non steroidal anti-inflammatory drug) did not stimulate any significant nociceptive behaviour. However, injection of eugenol (a pain relieving agent) induced the early phase not the tonic phase of nociceptive response. WMTA, eugenol or ketoprofen injection 20 min before formalin injection attenuated the first phase but somehow prevented the induction of the second phase of nociceptive responses which were produced by formalin. Behavioural nociceptive responses including shaking of the lower jaw and face rubbing were significantly reduced when the subject was pretreated with either WMTA or ketoprofen (P<0.001)., Conclusion: In this study, WMTA induced pain reduction by suppression of the formalininduced nociceptive response.

Riluzole has been shown to possess neuroprotective effects in a variety of neurological and animal model of diseases, including motor diseases. However, the mechanism(s) by which riluzole preserves the intrinsic electrophysiological characteristics of neuronal membrane has not been fully delineated. Ataxia is a clinical manifestation of disturbance in coordinated motor activity, which may be caused by cerebellar impairment. Here, the in vivo neuroprotective effect of riluzole on the intrinsic activity of Purkinje cells (PCs) in a rat model of cerebellar ataxia induced by 3-acetylpyridine (3-AP) was studied. Behavioural assessment tests, histological examination and whole cell patch clamp recording under current clamp conditions were used to explore the possible protective effect of riluzole against induction of ataxia with 3-AP treatment. Combined treatment with riluzole and 3-AP not only almost completely prevented the neuronal degeneration in cerebellar Purkinje cells layer but also the development of ataxia, which occurred following injection of 3-AP alone and partially improved the motor behaviour in comparison with ataxic rats. The normal firing behaviour and action potential characteristics of Purkinje neurones were preserved. The amplitude of both fast after hyperpolarization potential (fAHP) and post train after hyperpolarization potential, a marker of slow AHP (sAHP), along with the duration of post train AHP, which play an important role in regulating the firing behaviour were restored to the control conditions. These findings suggest that riluzole-induced neuroprotection may be mediated at least in part by activation of Ca(2+)-dependent K(+) channel function.