Post-tetanic Potentiation Research Articles

Changes in synaptic plasticity are associated with electroconvulsive shock-induced learning and memory impairment in rats with depression-like behavior.

BackgroundAccompanied with the effective antidepressant effect, electroconvulsive shock (ECS) can induce cognitive impairment, but the mechanism is unclear. Synaptic plasticity is the fundamental mechanism of learning and memory. This study aimed to investigate the effect of ECS on synaptic plasticity changes in rats with depression-like behavior.MethodsChronic unpredictable mild stress procedure was conducted to establish a model of depression-like behavior. Rats were randomly divided into the following three groups: control group with healthy rats (group C), rats with depression-like behavior (group D), and rats with depression-like behavior undergoing ECS (group DE). Depression-like behavior and spatial learning and memory function were assessed by sucrose preference test and Morris water test, respectively. Synaptic plasticity changes in long-term potentiation (LTP), long-term depression (LTD), depotentiation, and post-tetanic potentiation (PTP) were tested by electrophysiological experiment.ResultsECS could exert antidepressant effect and also induced spatial learning and memory impairment in rats with depression-like behavior. And, data on electrophysiological experiment showed that ECS induced lower magnitude of LTP, higher magnitude of LTD, higher magnitude of depotentiation, and lower magnitude of PTP.ConclusionECS-induced learning and memory impairment may be attributed to postsynaptic mechanism of LTP impairment, LTD and depotentiation enhancement, and presynaptic mechanism of PTP impairment.

Biological Spiking Synapse Constructed from Solution Processed Bimetal Core-Shell Nanoparticle Based Composites.

Inspired by the highly parallel processing power and low energy consumption of the biological nervous system, the development of a neuromorphic computing paradigm to mimic brain-like behaviors with electronic components based artificial synapses may play key roles to eliminate the von Neumann bottleneck. Random resistive access memory (RRAM) is suitable for artificial synapse due to its tunable bidirectional switching behavior. In this work, a biological spiking synapse is developed with solution processed Au@Ag core-shell nanoparticle (NP)-based RRAM. The device shows highly controllable bistable resistive switching behavior due to the favorable Ag ions migration and filament formation in the composite film, and the good charge trapping and transport property of Au@Ag NPs. Moreover, comprehensive synaptic functions of biosynapse including paired-pulse depression, paired-pulse facilitation, post-tetanic potentiation, spike-time-dependent plasticity, and the transformation from short-term plasticity to long-term plasticity are emulated. This work demonstrates that the solution processed bimetal core-shell nanoparticle-based biological spiking synapse provides great potential for the further creation of a neuromorphic computing system.

Structural engineering of tantalum oxide based memristor and its electrical switching responses using rapid thermal annealing

We have demonstrated the co-existence of reliable analog and digital switching characteristics with tantalum oxide based memristor by appropriate rapid thermal annealing (RTA). The device without RTA exhibits a digital SET and multilevel RESET for positive and negative sweeps, respectively. On the other hands, the device shows only analog switching characteristics such that current level increases and decreases gradually for successive positive and negative voltage sweeps, respectively, before any electroforming process with the RTA in the nitrogen ambient at the crystalline temperature of tantalum oxide which is 700 °C for 60 s. Once electroforming process is done, the device exhibits a reliable digital switching with SET at positive sweep and RESET at negative sweep voltages. In the analog state of the device we successfully emulate the synaptic characteristic of the device like spike-rate dependent plasticity (SRDP), pulse-paired facilitation (PPF) and post-tetanic potentiation (PTP). Finally, the Hermann Ebbinghaus forgetting curve is obtained from these devices. The conversion of the device from the digital SET and multilevel RESET to analogue switching is attributed to structural transition of amorphous tantalum oxide to polycrystalline tantalum oxide, different defect density and interface variation in the device.

Epinephrine augments posttetanic potentiation in mouse skeletal muscle with and without myosin phosphorylation.

Sympathetic tone may influence force potentiation, that is, the stimulation‐induced increase in skeletal muscle mechanical function associated with myosin phosphorylation, although the mechanism for this effect remains unknown. The purpose of this study was to examine the influence of epinephrine on concentric twitch force potentiation of wild‐type and skeletal myosin light‐chain kinase devoid mouse muscle (skMLCK −/−). To this end, concentric twitch force was assessed before and after a potentiating stimulus (PS) to determine the peak and the duration of potentiation in the absence (−EPI) and presence (+EPI) of 1 μmol/L epinephrine in both genotypes. Twitch force of wild‐type and skMLCK −/− muscles was increased by up to 31 and 35% and 18 and 23% in the −EPI and EPI conditions, respectively (all data n = 8, P < 0.05). In wild‐type muscles, the PS increased RLC phosphorylation from 0.14 ± 0.05 (rest) to 0.66 ± 0.08 mol phos mol RLC; by 480 sec RLC phosphorylation had returned to baseline (all data n = 4 each time point, P < 0.05). Neither resting nor peak levels of RLC phosphorylation were altered by +EPI, although the duration of RLC phosphorylation was prolonged. In skMLCK −/− muscles, RLC phosphorylation was not elevated above constituent levels by stimulation in either the −EPI or +EPI condition. Thus, given the similarity in potentiation responses between genotypes our data suggest that the influence of epinephrine on potentiation was independent of skMLCK catalyzed phosphorylation of the RLC, although the clinical significance of this pathway for skeletal muscle function remains to be identified.

P/Q-type Calcium Channel Antibodies in Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction. Approximately 50-60% of patients with LEMS have a tumor, most often small cell lung cancer (SCLC), making LEMS a paraneoplastic neurological syndrome. In Japan, the clinical picture is a male: female ratio of 3:1; mean age, 62 years (17-80 years); and 61% of LEMS patients have SCLC (SCLC-LEMS), with the remainder of patients having no cancer. Patients with LEMS develop a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes with post-tetanic potentiation, and autonomic symptoms. Interestingly, less than 10% of patients with LEMS have cerebellar ataxia (LEMS with paraneoplastic cerebellar degeneration). Considering its pathomechanisms, LEMS is a presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine is impaired by autoantibodies against P/Q-type voltage-gated calcium channels (P/Q-VGCCs) at active zones reducing quantal release of acetylcholine, although an animal model using immunization with purified P/Q-VGCCs has not yet been established. The diagnosis can be confirmed by finding a reduced compound muscle action potential amplitude that increases by over 60% following maximum voluntary activation or 50 Hz nerve stimulation. Approximately 90% of patients who satisfy the above electrophysiological diagnostic criteria are positive for P/Q-VGCC antibodies have their diagnosis confirmed. Specific tumor therapy in SCLC-LEMS will often improve the neurologic deficit. Tumor removal is the primary treatment for LEMS. If primary tumor screening is negative, screening should be repeated after 3-6 months, followed by screening every 6 months until 2 years post diagnosis. Most patients benefit from 3,4-diaminopyridine being administered with pyridostigmine. In those with severe weakness, high-dose intravenous gamma-globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone, alone or combined with immunosuppressive drugs, can achieve long-term control of the disorder. The results of a prospective cohort study showed that the presence of LEMS with SCLC had a significant survival advantage independent of other prognostic factors including disease extent, age, sex, performance status, and serum sodium values.

S12-2. Excitation-contraction coupling in myasthenia gravis: Up to date

Although defective neuromuscular transmission is known to be a cause of muscle weakness in myasthenia gravis (MG), previous studies have shown the possible roles of other processes, the failure of which may also cause muscle weakness in MG. Especially, excitation-contraction (E-C) coupling may be defective in patients with MG. Some investigators have applied the post-tetanic potentiation and/or the staircase phenomenon to elucidate the impairment of E-C coupling in MG. Recently, we reported a new method to assess E-C coupling of masseter and abductor pollicis brevis muscles using an accelerometer. In this method, compound muscle action potentials (CMAP) in the belly-tendon fashion and movement-related potentials (MRP) of jaw and finger movements were simultaneously recorded following nerve stimulation. The E-C coupling time (ECCT) was obtained from the difference in onset latencies between CMAP and MRP. The impairment of E-C coupling was assessed by prolonged ECCT and/or low MRP amplitude. In this lecture, I will discuss our data in MG, (1) correlation of bite force with ECCT of the masseter, (2) correlation between anti-ryanodine receptor antibody and ECCT, (3) early effect of tacrolimus in improving ECCT, (4) impairment of post-tetanic potentiation of muscle twitch, (5) effect of local cooling on E-C coupling.

Retraction: Protein kinase C is a calcium sensor for presynaptic short-term plasticity.

In presynaptic boutons, calcium (Ca(2+)) triggers both neurotransmitter release and short-term synaptic plasticity. Whereas synaptotagmins are known to mediate vesicle fusion through binding of high local Ca(2+) to their C2 domains, the proteins that sense smaller global Ca(2+) increases to produce short-term plasticity have remained elusive. Here, we identify a Ca(2+) sensor for post-tetanic potentiation (PTP), a form of plasticity thought to underlie short-term memory. We find that at the functionally mature calyx of Held synapse the Ca(2+)-dependent protein kinase C isoforms α and β are necessary for PTP, and the expression of PKCβ in PKCαβ double knockout mice rescues PTP. Disruption of Ca(2+) binding to the PKCβ C2 domain specifically prevents PTP without impairing other PKCβ-dependent forms of synaptic enhancement. We conclude that different C2-domain-containing presynaptic proteins are engaged by different Ca(2+) signals, and that Ca(2+) increases evoked by tetanic stimulation are sensed by PKCβ to produce PTP.DOI: http://dx.doi.org/10.7554/eLife.03011.001.

Translating Neuronal Activity at the Synapse: The Role of the Protein Kinase C Cascade in Short-Term Plasticity

Neurons dynamically regulate neurotransmitter release through many processes known collectively as synaptic plasticity. Post-tetanic potentiation (PTP) is a widespread form of synaptic plasticity that lasts for tens of seconds, and which may have important computational roles and contribute to short-term memory. According to a leading mechanism, the high-frequency stimulation that is necessary to induce PTP increases presynaptic calcium, which activates calcium sensors to regulate the amplitude and time-course of increased release. At the “Synaptic Vesicle Fusion and Retrieval” symposium, I will discuss our investigations into the role of the calcium-sensitive protein kinase C (PKC) as an essential regulator of PTP at 3 mammalian excitatory synapses: the parallel fiber - Purkinje cell synapse in the cerebellar cortex, the calyx of Held in the auditory brainstem, and the CA3 - CA1 synapse in the hippocampus. I will introduce a conditional knock-in approach to selectively mutate all PKC phosphorylation sites in the prominent PKC phosphorylation substrate Munc18-1, an SM family protein that is essential for release. Finally, I will describe initial efforts using this new mouse model to delineate the molecular events underlying enhanced neurotransmission during PTP.

Recent progress in memristors for stimulating synaptic plasticity

With the rapid expansion of data information, modern computers based on the von Neumann architecture are facing severe challenges. Intelligent computers that can learn, store, and process information flexibly like a human brain will be the direction and goal of computers development. Brain controls almost all the complex life activities of human beings, and information transmission between cerebral neurons relies on the structure called “synapse, whose outstanding property — synaptic plasticity— is thought to be an important molecular basis of learning and memory. Therefore, it is widely believed that emulation of synapse and synaptic plasticity is the first step to realize effective artificial neural networks. Owing to the birth and development of the fourth fundamental passive circuit elements, memristors, which have unique nonlinear synaptic electrical transmission characteristics, it is possible to achieve this goal. Thus, over the past few years, a great deal of efforts have been made in mimicking synapse functions though memristors. In this review, recent simulations of synaptic plasticity using different memristor devices and various methods are comprehensively summarized, including short-term plasticity (paired-pulse depression, paired-pulse facilitation, and post-tetanic potentiation), long-term plasticity, spiking-rate-dependent plasticity, spiking-timing-dependent plasticity, learning experience, associative memory, and synaptic scaling. Finally, the current problems faced in the research and the development prospects in this area are briefly discussed.

Neuroprotective Effects of Macrovipera lebetina Snake Venom in the Model of Alzheimer’s Disease

Pathological features of Alzheimer’s disease (AD) include accumulation and deposition of β-amyloid (Aβ) in the brain, activation of astrocytes and microglia, and disruption of cholinergic neurotransmission. In our experiments on rats, a model of AD was created by intracerebroventricular (i.c.v.) injections of Aβ25–35 amyloid. In another animal group, this was combined with intramuscular (i.m.) injections of small doses of Macrovipera lebetina (ML) snake venom (50 μl of 5% solution of an LD50 dose per animal seven times with one-day-long intervals). In the AD model, the most vulnerable neurons were found in the hippocampal fields CA1 and CA3. The phosphatase activity in the hippocampus of Aβ-injected rats sharply dropped. Systemic administration of small doses of ML venom induced positive changes in the structural characteristics of hippocampal neurons, increased the density of neurons in the above fields, normalized metabolism, and intensified Ca2+-dependent phosphorylation. Under the action of ML venom, the proportion of responses of hippocampal pyramidal neurons after high-frequency tetanic stimulation of the ipsilateral entorhinal cortex in the form of tetanic depression–posttetanic potentiation increased, and an overall increase in the firing rate of hippocampal neurons was observed. The intensity of free radical processes in some tissues of Aβ-affected animals became much lower under the action of ML venom. Thus, small doses of this venom manifest clear neuroprotective effects in the rat AD model.

Establishing a relationship between EQ-5D-5L and QMG in patients with Lambert-Eaton myasthenic syndrome

Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare presymptomatic disorder of neuromuscular transmission in which quantal release of acetylcholine is impaired, causing clinical characteristics including proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation, and autonomic changes, impacting a patient’s quality of life. LEMS is a para-neoplastic syndrome in 40-50% of patients, but can present in the absence of any underlying tumour. In Europe, Amifampridine (3,4-diaminopyridine) phosphate (Firdapse®) has been the only licensed treatment for LEMS since 2009.

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function.

The tarantula skeletal muscle X-ray diffraction pattern suggested that the myosin heads were helically arranged on the thick filaments. Electron microscopy (EM) of negatively stained relaxed tarantula thick filaments revealed four helices of heads allowing a helical 3D reconstruction. Due to its low resolution (5.0nm), the unambiguous interpretation of densities of both heads was not possible. A resolution increase up to 2.5nm, achieved by cryo-EM of frozen-hydrated relaxed thick filaments and an iterative helical real space reconstruction, allowed the resolving of both heads. The two heads, "free" and "blocked", formed an asymmetric structure named the "interacting-heads motif" (IHM) which explained relaxation by self-inhibition of both heads ATPases. This finding made tarantula an exemplar system for thick filament structure and function studies. Heads were shown to be released and disordered by Ca2+-activation through myosin regulatory light chain phosphorylation, leading to EM, small angle X-ray diffraction and scattering, and spectroscopic and biochemical studies of the IHM structure and function. The results from these studies have consequent implications for understanding and explaining myosin super-relaxed state and thick filament activation and regulation. A cooperative phosphorylation mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 mono-phosphorylated free heads, explains super-relaxation, force potentiation and post-tetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction.

Systemic LPS resulted in a transient hippocampus malfunction but a prolonged corpus callosum injury

BackgroundTo investigate the effect of systemic lipopolysaccharide (LPS) on function of hippocampus and corpus callosum (CC) in adult rats.MethodsAdult rats with mature white matter tract were divided into systemic LPS and saline injection groups. Animal were euthanized following 3 daily injections (day 3) and 3-day after cessation of injections (day 6). At both time points, hippocampal long term potentiation (LTP) and CC compound action potentials (CAP) were recorded, beta amyloid precursor protein (β-APP) level in CC tissue was measured by Western blot, and microglia activation was examined by immunostaining and proportional area analysis.ResultsSystemic LPS significantly decreased amplitude of both post tetanic potentiation (PTP) and LTP at day 3, but PTP and LTP turned to be normal at day 6. CAP was significantly declined at day 3 but was further declined at day 6. The β-APP levels in CC tissues of LPS injected rats were significantly higher than that of saline group at both time-points. Interestingly, proportional area measurement disclosed that microglial areas in both hippocampus and CC significantly expanded at day3, but at the day 6, microglial area decreased in hippocampus but further increased in CC.ConclusionSystemic LPS resulted in a transient hippocampus malfunction but a prolonged CC injury. Microglia activation may correlate with such LPS induced white matter injury.

Ethanol Mediated Inhibition of Synaptic Vesicle Recycling at Amygdala Glutamate Synapses Is Dependent upon Munc13-2.

Chronic exposure to alcohol produces adaptations within the basolateral amygdala (BLA) that are associated with the development of anxiety-like behaviors during withdrawal. In part, these adaptations are mediated by plasticity in glutamatergic synapses occurring through an AMPA receptor mediated form of post-synaptic facilitation in addition to a unique form of presynaptic facilitation. In comparison to the post-synaptic compartment, relatively less is understood about the mechanisms involved in the acute and chronic effects of ethanol in the presynaptic terminal. Previous research has demonstrated that glutamatergic terminals in the mouse BLA are sensitive to ethanol mediated inhibition of synaptic vesicle recycling in a strain-dependent fashion. Importantly, the strain-dependent differences in presynaptic ethanol sensitivity are in accordance with known strain-dependent differences in ethanol/anxiety interactions. In the present study, we have used a short-hairpin RNA to knockdown the expression of the presynaptic Munc13-2 protein in C57BL/6J mice, whose BLA glutamate terminals are normally ethanol-insensitive. We injected this shRNA, or a scrambled control virus, into the medial prefrontal cortex (mPFC) which sends dense projections to the BLA. Accordingly, this knockdown strategy reduces the expression of the Munc13-2 isoform in mPFC terminals within the BLA and alters presynaptic terminal function in C57BL/6J mice in a manner that phenocopies DBA/2J glutamate terminals which are normally ethanol-sensitive. Here, we provide evidence that manipulation of this single protein, Munc13-2, renders C57BL/6J terminals sensitive to ethanol mediated inhibition of synaptic vesicle recycling and post-tetanic potentiation. Furthermore, we found that this ethanol inhibition was dose dependent. Considering the important role of Munc13 proteins in synaptic plasticity, this study potentially identifies a molecular mechanism regulating the acute presynaptic effects of ethanol to the long lasting adaptations in the BLA that occur during chronic ethanol exposure.

PKC\u03b1-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory

Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1SA/SA knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant alterations in the expressions of presynaptic function-related genes. Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1 (HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is involved in the regulation of presynaptic gene expression and subsequently regulates the hippocampus-dependent memory in phosphorylation-dependent manner.

Pre- and Postsynaptic Mechanisms of the Deprivation Potentiation of Neuron Population Responses in Rat Hippocampal Field CA1

Studies using in vitro rat hippocampal slices addressed the mechanism of deprivation potentiation (DeP) of neuron population responses in field CA1 developing as a result of prolonged (60 or 120 min) cessation of rare (0.05 Hz) test stimuli of Schaffer collaterals (SC). The development of DeP was found to involve two independent mechanisms: pre- and postsynaptic, responsible for induction of the short-term and long-term components of DeP, respectively. These studies showed that the interaction of DeP and long-term post-tetanic potentiation (LTP) is competitive in nature, providing evidence of similarity in the mechanisms of the long-term phase of DeP and the phase of LTP associated with protein phosphorylation. Our investigation showed that the Ca2+-dependent mechanism of induction of the postsynaptic component of DeP does not involve NMDA receptors, but does involve purine P2 receptors. A common curve for the relationship between the efficiency of synaptic transmission and the use/non-use of synapses including DeP, long-term depression (LTD), and LTP zones is presented.

Presenilins regulate synaptic plasticity and mitochondrial calcium homeostasis in the hippocampal mossy fiber pathway

BackgroundPresenilins play a major role in the pathogenesis of Alzheimer’s disease, in which the hippocampus is particularly vulnerable. Previous studies of Presenilin function in the synapse, however, focused exclusively on the hippocampal Schaffer collateral (SC) pathway. Whether Presenilins play similar or distinct roles in other hippocampal synapses is unknown.MethodsTo investigate the role of Presenilins at mossy fiber (MF) synapses we performed field and whole-cell electrophysiological recordings and Ca2+ imaging using acute hippocampal slices of postnatal forebrain-restricted Presenilin conditional double knockout (PS cDKO) and control mice at 2 months of age. We also performed quantitative electron microscopy (EM) analysis to determine whether mitochondrial content is affected at presynaptic MF boutons of PS cDKO mice. We further conducted behavioral analysis to assess spatial learning and memory of PS cDKO and control mice at 2 months in the Morris water maze.ResultsWe found that long-term potentiation and short-term plasticity, such as paired-pulse and frequency facilitation, are impaired at MF synapses of PS cDKO mice. Moreover, post-tetanic potentiation (PTP), another form of short-term plasticity, is also impaired at MF synapses of PS cDKO mice. Furthermore, blockade of mitochondrial Ca2+ efflux mimics and occludes the PTP deficits at MF synapses of PS cDKO mice, suggesting that mitochondrial Ca2+ homeostasis is impaired in the absence of PS. Quantitative EM analysis showed normal number and area of mitochondria at presynaptic MF boutons of PS cDKO mice, indicating unchanged mitochondrial content. Ca2+ imaging of dentate gyrus granule neurons further revealed that cytosolic Ca2+ increases induced by tetanic stimulation are reduced in PS cDKO granule neurons in acute hippocampal slices, and that inhibition of mitochondrial Ca2+ release during high frequency stimulation mimics and occludes the Ca2+ defects observed in PS cDKO neurons. Consistent with synaptic plasticity impairment observed at MF and SC synapses in acute PS cDKO hippocampal slices, PS cDKO mice exhibit profound spatial learning and memory deficits in the Morris water maze.ConclusionsOur findings demonstrate the importance of PS in the regulation of synaptic plasticity and mitochondrial Ca2+ homeostasis in the hippocampal MF pathway.

Prenatal melamine exposure induces impairments of spatial cognition and hippocampal synaptic plasticity in female adolescent rats

Developmental exposure to melamine induces long-term effects on brain and behavior in male rodents. To examine whether this prenatal event damages cognitive function in female offspring, we evaluated the behavioral effects and further attempted to investigate synaptic function. Prenatal melamine exposure (PME) was given by oral treatment to pregnant females through the whole gestational days with 400mg/day/kg bodyweight. On postnatal day (PD) 36, female offspring were assessed for spatial cognition in the Morris Water Maze (MWM) test. Simultaneously, the alterations in hippocampal synaptic plasticity in Schaffer collaterals-CA1 pathway in vivo were measured. The results of behavioral test showed that PME lead serious deficits of memory and re-acquisition abilities. PME depressed depotentiation in the hippocampal CA1 area of the PME group, but no alteration in LTP. Furthermore, variations of post-tetanic potentiation (PTP) and paired-pulse facilitation (PPF) were also observed in this pathway. This finding indicated that the PME affected spatial cognition in adolescent females, and the impairment of hippocampal synaptic functions may partly play a significant role in these effects.

The Mobility of AMPA-Type Glutamate Receptors as a Key Factor in the Expression and Maintenance of Synaptic Potentiation

The dynamics of the expression of post-tetanic potentiation of the focal response (the P spike) in the synaptic system consisting of Schaffer collaterals and field CA1 pyramidal neurons were studied in hippocampal slices from ICR mice. Potentiation was induced by high-frequency stimulation of Schaffer collaterals (1 sec, 100 Hz). At 10 sec, all slices in the group demonstrated an increase in the amplitude of the P spike in response to test stimuli. Slices with sharp increases in amplitude to maximal levels were seen, along with slices showing smooth increases in P-spike amplitude. Studies with the transport vesicle formation blocker brefeldin A assessed the relationship between the dependence of the phase of post-tetanic potentiation on intracellular transport. Brefeldin A was added to the perfusion solution before tetanic stimulation. This treatment of slices for 60 min had no effect on the magnitude of the basal P spike or the expression of post-tetanic potentiation, though it impaired the subsequent phase, i.e., maintenance of potentiation. A drop in P-spike amplitude was seen. The integrative activity of the system supporting the delivery of glutamate receptors to dendritic spines in the numbers and at the times required for rapid changes in and prolonged maintenance of the effectiveness of neurotransmission is discussed.

PECULIARITIES OF GANGLIONIC CONDUCTION OF EXCITATION AFTER DEPANCREATIZATION

Aim. To study the vegetative ganglion function after partial ablation of the pancreas. Materials and methods. Electrical activity of the postganglionic trunk fibers of the upper cervical sympathetic ganglion, with preganglionars stimulated by the rectangular impulse of supramaximal strength of 0,5 msec duration, was studied on 42 animals in the control and after depancreatization. Acetylcholine (AC) content in the ganglion before and after partial depancreatization, excitation conduction velocity by preganglionic fibers, amplitude and duration of postganglionic fibers action potential (AP), lability with stimulation of 10-40 Hz, posttetanic potentiation (PTP) was investigated. To assess the reliability of differences, Student’s t test was used. Critical significance level when controlling statistical hypotheses was accepted as equal to 0,05. Results. Ganglionic acetylcholine content on the day 9 after pancreatectomy decreased by three times. It was accompanied by the reduction of velocity of excitation spreading along the preganglionic fibers of the upper cervical sympathetic ganglion. Simultaneously, growth of latent period duration and postganglionic trunk action potential was registered. Development of pessimum with stimulation frequency of 20-40 Hz is significantly quickened, but posttetanic potentiation, typical for ganglion, completely disappears and is changed by the posttetanic depression. It proves fall in lability and functional properties of vegetative ganglion in the operated animals. Conclusions. Introduction of acetylcholine and lipocaic fully or partially compensated the occurring impairment of ganglionic conduction of excitation.