INDUCTION OF SPINAL LONG-TERM SYNAPTIC POTENTIATION IS SENSITIVE TO INHIBITION OF NEURONAL NOS IN L5 SPINAL NERVE-TRANSECTED RATS

The role of neuronal nitric oxide synthase (nNOS) in the central mechanism of neuropathic pain and long-term potentiation (LTP) of peripheral afferents remains obscure. The current study investigated the effect of intrathecal application of 7-nitroindazole (7-NI), a selective nNOS inhibitor (8.15 μg/5μl), on mechanical allodynia on day 14 after L5 spinal nerve transection. Furthermore, using in vivo single unit extracellular recording, we examined the effect of 7-NI on the induction of LTP of Aδ- and C-fiber-evoked responses. We have demonstrated that 7-NI attenuates nerve-injury-evoked mechanical allodynia. Additionally, our electrophysiological study has shown that the spinal administration of 7-NI significantly inhibits the induction of the LTP of Aδ- and C-fiber-evoked responses on day 14 after neuropathy. These data suggest that activation of nNOS may be crucial for the induction of the spinal LTP of Aδ- and C-fiber-evoked responses following peripheral nerve damage

Paired-pulse Inhibition and Disinhibition of the Dentate Gyrus Following Orexin Receptors Inactivation in the Basolateral Amygdala

Introduction: The Basolateral Amygdala (BLA) substantially affects neuronal transmission and synaptic plasticity processes through the dentate gyrus. Orexin neuropeptides play different roles in the sleep/wakefulness cycle, feeding, learning, and memory. The present study aimed to investigate the function of the orexin receptors of the BLA in the hippocampal local interneuron circuits.  Methods: For this, the region’s paired-pulse responses from the Dentate Gyrus (DG) were recorded. Within the procedure, SB-334867-A (12μg/0.5μL) and TCS-OX2-29 (10μg/0.5μL (orexin 1 & 2 receptors antagonists, respectively), were administered into both sides of the BLA areas of the rat brain. Dimethyl Sulfoxide (DMSO) was used as the solvent in the control animals with a volume of 0.5μL. Results: Our data indicated that the Paired-pulse (PP) responses were not affected by the inactivation of the orexin receptors of the BLA. Conclusion: Due to not observing any significant changes in the short form of synaptic plasticity, after inactivation of the orexin system of the BLA, we hypothesize that the orexinergic fibers to the basolateral part of the amygdala influence the long-term synaptic efficacy; however, the primary processing of information in short-term plasticity model is not affected by the same system. The elementary processing of the data by the amygdala might happen through the action of other neurotransmitter systems

The Effect of glial cells inhibition on the progression of seizures induced by chemical kindling in male rats

Background &amp; Objectives: Considering the role of glial cells in synaptic transmission, regulation of neurotransmitter concentration in synaptic cleft, K+ buffering, and releasing the gliotransmitters, the purpose of this study is to investigate the effect of glial cells inhibition on the progression of seizures induced by chemical kindling in rats. Materials &amp; Methods: In chemical kindling, animals received Pentylenetetrazol, 35 mg/kg each 48 hours, intraperitoneally and five different stages of seizure were appeared gradually and seizure parameters including maximum seizure stage (SS), stage 4 latency (S4L), stage 4&amp;5 duration (S5D), and seizure duration (SD) were measured during 20 min after PTZ injection. Then seizure parameters were evaluated in animals treated with intracerebroventricular (icv) administration of Fluorocitrate (as a glial cells inhibitor), injected 30 min before PTZ, and compared with PTZ treated animals. Results: Results showed that glial cells inhibition with ICV injection of Fluorocitrate decreased SS, S5D, and SD and increased S4L significantly (P<0.05, P<0.01, P<0.001). Â Conclusion: On the basis of obtained results, it may be concluded that glial cells inhibition reduces spreading rate of epileptiform activity in the nervous system, and the duration of neuronal hyperexcitability and, also, prevents the progression of seizure to final stages

The role of glial glutamate transporter in the baseline synaptic response and short-term synaptic plasticity of CA1 area of the hippocampus in male Wistar rat

Background. Glial cells release different gliotransmitters and response to neurotransmitters released from neurons. These cells especially astrocytes, having different transporters, play an important role in synaptic space homeostasis and synaptic plasticity. In this study, the role of hippocampal glial glutamate transporter (EAAT2) in baseline synaptic response and short term synaptic plasticity were investigated. Methods. In this experimental study, ceftriaxone, EAAT2 activator (0.5mmol/0.5μl), was microinjected intrahippcampally for activation of hippocampal glial glutamate transporter in male wistar rats. Baseline synaptic response and short term synaptic plasticity were evaluated by field potential recording. fEPSP was recorded from CA1 following Schaffer collaterals stimulation. After Input/Output curve construction, short term synaptic plasticity was induced by paired pulse stimulations. Results. Activation of EAAT2 by ceftriaxone microinjection in CA1 did not have any effect on baseline synaptic response (P> 0.05, Two Way ANOVA). There was no significant difference in Paired Pulse Index at 20, 80, and 200 ms inter-pulse interval between ceftriaxone treated and control group (P> 0.05, Two Way ANOVA). Conclusion. The results suggest that hippocampal glial glutamate transporter activation does not have effect on baseline synaptic response and short term synaptic plasticity in CA1 area of the hippocampus. Practical implications. Considering the role of glial cells in regulating the excitability of the nervous system as well as synaptic plasticity, correcting these features of the nervous system by manipulating glial cells can help the treatment or prevention of neurological diseases. In this study, the role of glial cells in the homeostasis of the glutamate in the synaptic space of the hippocampus was evaluated, through the stimulation of its uptake, on the basic synaptic activity and short-term synaptic plasticity

The Role of Astrocytic Cx43 in Baseline Synaptic Response and Short Term Synaptic Plasticity in CA1 Area of the Hippocampus

Background and purpose: Astrocytic connexins (Cxs) play roles in ion diffusion to the extracellular milieu and in release of ATP and gliotransmitters including glutamate. Connexin 43 (Cx43) is one of the most abundant Cxs in brain tissue, especially in the hippocampus, so, we investigated its role on CA1 baseline synaptic response and short term synaptic plasticity. Materials and methods: In this experimental study, bilateral intrahippocampal microinjection of TAT-Gap19, Cx43 blocker (1nmol/1μl) was performed for inhibition of hippocampal astrocytic connexin 43. Baseline synaptic response and short term synaptic plasticity were evaluated by field potential recording. Results:  According to two-way ANOVA, inhibition of hippocampal Cx43 did not have any effect on baseline synaptic response (P>0.05). TAT-Gap19 decreased paired pulse index (PPI) at 20 and 80 ms inter pulse intervals (IPI, Unpaired t-test, P0.05). Conclusion: The results suggest that the function of hippocampal astrocytic Cx43 does not affect baseline synaptic response but affects short term synaptic plasticity in CA1 area of the hippocampus

Characterization of Functional Effects of Two New Active Fractions Isolated From Scorpion Venom on Neuronal Ca2+ Spikes: A Possible Action on Ca2+-Dependent Dependent K+ Channels

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 Ca2+-activated K+ channel blocker, reduced the amplitude of AHP, enhanced the firing frequency of calcium spikes and broadened the duration of Ca2+ 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

Suppressive Effects of Resveratrol Treatment on The Intrinsic Evoked Excitability of CA1 Pyramidal Neurons

Objective: Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neuronal function, little effort, if any, has been made to investigate the cellular effect of resveratrol treatment on intrinsic neuronal properties. Materials and Methods: This experimental study was performed to examine the acute effects of resveratrol (100 μM) on the intrinsic evoked responses of rat Cornu Ammonis (CA1) pyramidal neurons in brain slices, using whole cell patch clamp recording under current clamp conditions. Results: Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant (P<0.05) increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential (AP) when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol. Conclusion: Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity