Post-tetanic Potentiation Research Articles

Energy-Efficient Artificial Synapses Based on Oxide Tunnel Junctions.

The development of artificial synapses has enabled the establishment of brain-inspired computing systems, which provides a promising approach for overcoming the inherent limitations of current computer systems. The two-terminal memristors that faithfully mimic the function of biological synapses have intensive prospects in the neural network field. Here, we propose a high-performance artificial synapse based on oxide tunnel junctions with oxygen vacancy migration. Both short-term and long-term plasticities are mimicked in one device. The oxygen vacancy migration through oxide ultrathin films is utilized to manipulate long-term plasticity. Essential synaptic functions, such as paired pulse facilitation, post-tetanic potentiation, as well as spike-timing-dependent plasticity, are successfully implemented in one device by finely modifying the shape of the pre- and postsynaptic spikes. Ultralow femtojoule energy consumption comparable to that of the human brain indicates its potential application in efficient neuromorphic computing. Oxide tunnel junctions proposed in this work provide an alternative approach for realizing energy-efficient brain-like chips.

Neonatal Proinflammatory Stress and Deficit of Induction of Long-Term Potentiation in the Hippocampus in Rats: Gender Differences

The characteristics of long-term potentiation (LTP) in field CA1 of living hippocampal slices from rats aged 17–33 days were studied after neonatal administration of bacterial lipopolysaccharide (LPS) to evaluate the long-term effects of neuroinflammation in early ontogeny on synaptic plasticity. A deficit of LTP was seen in field CA1 of the hippocampus of rats surviving neonatal proinflammatory stress (NPS), the most sensitive being the mechanism of induction. In rats of the NPS group, synaptic potentiation was absent or weak in 61% of experiments, though when normal induction occurred, LTP persisted throughout the observation period. Correlation analysis showed that impairments to the development of the mechanisms of long-term plasticity in response to NPS are probably associated with weakening of the afferent influx to hippocampal neurons. Initially low-amplitude responses in field CA1 to application of single stimuli to Schaffer collaterals dominated in the hippocampus of female rats of the NPS group but were significantly rarer in males. This is probably why the early phase of potentiation in living hippocampal slices from females was virtually absent, though slow potentiation gradually developed. The hippocampus of males of the NPS group showed a statistically significant link between the effects of suppression of LTP and synaptic depression of initial potentials; signs of convulsive activity appeared when potentiation was successful. In contrast to males and the results obtained from all control groups, the hippocampus of female rats showed facilitation of the development of post-tetanic potentiation. It is suggested that this effect may be relevant to protective functions, which are evidently less effectively utilized in the hippocampus of males.

Post-tetanic potentiation at the hippocampal mossy fiber–CA3 pyramidal neuron synapse shows a low induction threshold and is mediated by an increase in the readily releasable vesicle pool

Post-tetanic potentiation at the hippocampal mossy fiber–CA3 pyramidal neuron synapse shows a low induction threshold and is mediated by an increase in the readily releasable vesicle pool

Presynaptic mechanisms underlying post-tetanic potentiation at hippocampal mossy fiber synapses

Presynaptic mechanisms underlying post-tetanic potentiation at hippocampal mossy fiber synapses

Post-tetanic Potentiation and Depression in Hippocampal Neurons in a Rat Model of Alzheimer’s Disease: Effects of Teucrium Polium Extract

The plant Teucrium polium (T.p.) possesses a wide range of pharmacological activities due to the presence, in particular, of different phytochemicals, phenols and flavonoids. We examined the effects of the T.p. extract on impulse activity of hippocampal neurons in rats with a model of Alzheimer’s disease. Adult albino rats were divided into three groups (5 animals in each). The control group C obtained intracerebroventricular (i.c.v.) infusions of saline, animals of group Aβ were i.c.v. infused with amyloid β peptide 25–35, Aβ(25–35), and group Aβ+T.p. was treated by both Aβ(25–35) infusions and introductions of the T.p. extract. In group Aβ, a greater proportion of hippocampal neurons with post-tetanic depression after high-frequency stimulation of the entorhinal cortex, lower values of the frequency of background activity generated by the above neurons, and relatively weaker modifications of spike activity (post-tetanic potentiation and depression) were observed. Daily administrations of the T.p. extract partially but considerably reversed the above-mentioned negative shifts in spike activity of hippocampal neurons caused by Aβ(25–35). We suggest that T.p. extract containing important phytochemicals is capable of ameliorating the memory dysfunction caused by Aβ(25–35) via blocking amyloid deposition and a positive influence on the functions of hippocampal neurons.

Flexible oxide neuromorphic transistors with synaptic learning functions

Realization of brain-inspired hardware devices is deemed to be a significant step for constructing a neuromorphic system. Moreover, flexible bioinspired neuromorphic devices have broad applications in bioinspired intelligent electronics. Here, we propose flexible IWO neuromorphic transistors gated with proton-conducting chitosan-based electrolytes. The transistor exhibits a low subthreshold swing of ~112 mV/dec and a high mobility of ~17 cm2 V−1 s−1. Moreover, the transistor exhibits excellent mechanical robustness against mechanical stress. Some crucial synaptic functions in biological synapses are mimicked on the proposed flexible transistor, including excitatory post-synaptic currents, paired-pulse facilitation, post-tetanic potentiation, etc. Most importantly, ‘learning-experience’ behaviors are implemented in the device. The proposed flexible neuromorphic devices have applications in artificial perception learning systems, including electronic skin and personal health monitoring.

The Onset and Progression of Hippocampal Synaptic Plasticity Deficits in the Q175FDN Mouse Model of Huntington Disease.

Huntington disease (HD) is an inherited neurodegenerative disease characterized by a clinical triad of motor, psychiatric and cognitive symptoms. HD is caused by a CAG repeat expansion in the gene encoding the huntingtin protein. Homozygosity for the HD-causing mutation is extremely rare; thus, the majority of HD patients express the mutant huntingtin protein in addition to reduced levels of the non-pathogenic huntingtin protein. Deficits in synaptic plasticity, including hippocampal long-term potentiation (LTP), have been identified in various mouse models of HD and are thought to contribute to the debilitating cognitive symptoms associated with the disease. However, the bulk of these studies used N-terminal fragment or homozygous knock-in mouse models of HD at symptomatic ages, and our understanding of the onset and progression of synaptic plasticity deficits in the HD brain is lacking. To better understand the time-course of synaptic plasticity deficits in HD, as well as the impact of heterozygous and homozygous huntingtin mutations, we quantified basal synaptic connectivity, presynaptic release probability, presynaptically mediated post-tetanic potentiation (PTP) and postsynaptically mediated LTP at presymptomatic, early symptomatic and late symptomatic ages in heterozygous and homozygous Q175FDN knock-in HD mice. Our results demonstrate clear age-dependent effects of the HD-causing mutation on both short and long-term plasticity that generally emerge earlier in homozygous mice. Interestingly, deficits in presynaptic short-term plasticity were more closely linked to disease progression than deficits in postsynaptic LTP, and heterozygous mice were more susceptible to an LTP deficit when induced by high frequency stimulation compared to theta burst stimulation. To the best of our knowledge, the present study represents the most thorough characterization to date of the onset and progression of hippocampal synaptic plasticity deficits in a mouse model of HD, and should prove valuable to future studies exploring cellular mechanisms underlying the debilitating cognitive decline in HD.

Assessment of glutamatergic synaptic transmission and plasticity in brain slices: relevance to bioelectronic approaches

BackgroundGlutamatergic neurons represent the largest neuronal class in the brain and are responsible for the bulk of excitatory synaptic transmission and plasticity. Abnormalities in glutamatergic neurons are linked to several brain disorders and their modulation represents a potential opportunity for emerging bioelectronic medicine (BEM) approaches. Here, we have used a set of electrophysiological assays to identify the effect of the pyrimidine nucleoside uridine on glutamatergic systems in ex vivo brain slices. An improved understanding of glutamatergic synaptic transmission and plasticity, through this type of examination, is critical to the development of potential neuromodulation strategies.MethodsEx vivo hippocampal slices (400 μm thick) were prepared from mouse brain. We recorded field excitatory postsynaptic potentials (fEPSP) in the CA1’s stratum radiatum by stimulation of the CA3 Schaeffer collateral/commissural axons. Uridine was applied at concentrations (3, 30, 300 μM) representing the physiological range present in brain tissue. Synaptic function was studied with input-output (I-O) functions, as well as paired-pulse facilitation (PPF). Synaptic plasticity was studied by applying tetanic stimulation to induce post-tetanic potentiation (PTP), short-term potentiation (STP) and long-term potentiation (LTP). Additionally, we determined whether uridine affected synaptic responses carried solely by n-methyl-d-aspartate receptors (NMDARs), particularly during the oxygen-glucose deprivation (OGD) paradigm.ResultsThe presence of uridine altered glutamatergic synaptic transmission and plasticity. We found that uridine affected STP and LTP in a concentration-dependent manner. Low-dose uridine (3 μM) had no effect, but higher doses (30 and 300 μM) impaired STP and LTP. Moreover, uridine (300 μM) decreased NMDAR-mediated synaptic responses. Conversely, uridine (at all concentrations tested) had a negligible effect on PPF and basal synaptic transmission, which is mediated primarily by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). In addition, uridine (100 μM) exerted a protective effect when the hippocampal slices were challenged with OGD, a widely used model of cerebral ischemia.ConclusionsUsing a wide set of electrophysiological assays, we identify that uridine interacts with glutamatergic neurons to alter NMDAR-mediated responses, impair synaptic STP and LTP in a dose-dependent manner, and has a protective effect against OGD insult. This work outlines a strategy to identify deficits in glutamatergic mechanisms for signaling and plasticity that may be critical for targeting these same systems with BEM device-based approaches. To improve the efficacy of potential neuromodulation approaches for treating brain dysfunction, we need to improve our understanding of glutamatergic systems in the brain, including the effects of modulators such as uridine.

Proposal for a Revised Classification of the Depth of Neuromuscular Block and Suggestions for Further Development in Neuromuscular Monitoring.

Proposal for a Revised Classification of the Depth of Neuromuscular Block and Suggestions for Further Development in Neuromuscular Monitoring.

Effect of Interleukin-10 on Localization of AMPA Receptors in Synapses during Long-Term Posttetanic Potentiation in Cultured Hippocampal Slices.

The effect of the anti-inflammatory cytokine IL-10 on the ultrastructural distribution of AMPA receptor GluR1 subunit in CA1 field of cultured hippocampal slices was studied by using immunohistochemical technique. It was found that long-term posttetanic potentiation increased the content of GluR1 in the postsynaptic density of the axo-spinous synapse. Addition of IL-10 in concentrations of 1 and 10 ng/ml to the medium facilitated long-term posttetanic potentiation thereby changing the distribution of GluR1 in the spine: the number of receptors increased in the cytoplasm and decreased in the postsynaptic density. It is assumed that activation of neuronal IL-10 receptors affects the distribution of AMPA receptors in axo-spinous synapses of hippocampal field CA1 through interplay of intracellular signaling pathways, thereby participating in the mechanisms of synaptic plasticity under normal conditions.

Early existence and biochemical evolution characterise acutely synaptotoxic PrPSc.

Although considerable evidence supports that misfolded prion protein (PrPSc) is the principal component of “prions”, underpinning both transmissibility and neurotoxicity, clear consensus around a number of fundamental aspects of pathogenesis has not been achieved, including the time of appearance of neurotoxic species during disease evolution. Utilizing a recently reported electrophysiology paradigm, we assessed the acute synaptotoxicity of ex vivo PrPSc prepared as crude homogenates from brains of M1000 infected wild-type mice (cM1000) harvested at time-points representing 30%, 50%, 70% and 100% of the terminal stage of disease (TSD). Acute synaptotoxicity was assessed by measuring the capacity of cM1000 to impair hippocampal CA1 region long-term potentiation (LTP) and post-tetanic potentiation (PTP) in explant slices. Of particular note, cM1000 from 30% of the TSD was able to cause significant impairment of LTP and PTP, with the induced failure of LTP increasing over subsequent time-points while the capacity of cM1000 to induce PTP failure appeared maximal even at this early stage of disease progression. Evidence that the synaptotoxicity directly related to PrP species was demonstrated by the significant rescue of LTP dysfunction at each time-point through immuno-depletion of >50% of total PrP species from cM1000 preparations. Moreover, similar to our previous observations at the terminal stage of M1000 prion disease, size fractionation chromatography revealed that capacity for acute synpatotoxicity correlated with predominance of oligomeric PrP species in infected brains across all time points, with the profile appearing maximised by 50% of the TSD. Using enhanced sensitivity western blotting, modestly proteinase K (PK)-resistant PrPSc was detectable at very low levels in cM1000 at 30% of the TSD, becoming robustly detectable by 70% of the TSD at which time substantial levels of highly PK-resistant PrPSc was also evident. Further illustrating the biochemical evolution of acutely synaptotoxic species the synaptotoxicity of cM1000 from 30%, 50% and 70% of the TSD, but not at 100% TSD, was abolished by digestion of immuno-captured PrP species with mild PK treatment (5μg/ml for an hour at 37°C), demonstrating that the predominant synaptotoxic PrPSc species up to and including 70% of the TSD were proteinase-sensitive. Overall, these findings in combination with our previous assessments of transmitting prions support that synaptotoxic and infectious M1000 PrPSc species co-exist from at least 30% of the TSD, simultaneously increasing thereafter, albeit with eventual plateauing of transmitting conformers.

Effect of TGF-beta1 on long-term synaptic plasticity and distribution of AMPA receptors in the CA1 field of the hippocampus

Using the methods of electrophysiology and immunohistochemistry, the effect of the transforming factor beta-1(TGF-β1), an anti-inflammatory cytokine, on the long-term post-tetanic potentiation (LTP) in CA1 field hippocampal slices and the distribution of the GluR1 subunit of the AMPA receptor has been studied.It was shown that TGF-β1 at a concentration of 10 ng/ml did not significantly affect the initial stage of LTP and substantially changed the distribution of synaptic AMPA receptors in response to tetanic stimulation. Twenty five minutes after the tetanization, the main pool of AMPA receptors (90%) was due to the postsynaptic density (PSD). By contrast, LTP in the presence of TGF-β1 was accompanied by less pronounced changes in the distribution of AMPA receptors. Their localization in both pre- and postsynaptic regions remained nearly the same as that in the control. It may be suggested that the normal distribution of AMPA receptors in spinous synapses promotes the stabilization of potentiated synapses, thereby retaining LTP for longer terms.

Lack of influence of estrogen on myosin phosphorylation and post-tetanic potentiation in muscles from young adult C57BL mice

Estrogen influences myosin phosphorylation and post-tetanic potentiation in murine fast muscle. We tested the hypothesis that this influence is mediated by estrogen effects on skeletal myosin light chain kinase (skMLCK) activity. To this end, extensor digitorum longus muscles from female wildtype and skMLCK-absent (skMLCK-/-) mice were grouped as follows: ovariectomized with estrogen (E+), ovariectomized without estrogen (E-), sham surgery, and intact baseline. At 8 weeks of age, the ovariectomized groups were ovariectomized followed by implantation of either a 0.1 mg 17β-estradiol (E+) or placebo pellet (E-). Two weeks later, muscles were isolated and suspended in vitro (25° C) for determination of regulatory light chain phosphorylation and post-tetanic potentiation. Regulatory light chain phosphorylation was not different across conditions within either genotype although wildtype values were significantly greater than skMLCK-/- values. Consistent with this, the potentiation of concentric twitch force was similar between E+ and E- groups within each genotype but wildtype values were greater than skMLCK-/- values. However, unaltered estradiol levels following ovariectomy, likely due to previously underappreciated confounds of mouse age, development, and growth during estrogen supplementation, prevented direct testing of the hypothesis. Future studies should note the importance of estrous cycles and continuing physiological developments of young adult mice when working with ovarian hormones.

Proposal for a Revised Classification of the Depth of Neuromuscular Block and Suggestions for Further Development in Neuromuscular Monitoring

Proposal for a Revised Classification of the Depth of Neuromuscular Block and Suggestions for Further Development in Neuromuscular Monitoring

Tunable synaptic behavior realized in C3N composite based memristor

Inspired by the parallel performing of storage and processing information in biological synapse, artificial synapse that can control ionic and protonic currents are ideal means for attracted tremendous attention as a promising option to break the von Neumann bottleneck. Here we demonstrate an artificial synapse with tunable synaptic behavior based on solution-processed two-dimensional (2D) C3N/polyvinylpyrrolidone (PVPy). The proton modulated memristive characteristics of synaptic device are verified by ambient pressure X-ray photoelectron spectroscopy under different H2O gas atmosphere. The highly proton conducting of C3N/PVPy matrix stems from the hydrogen bonding network between C3N and PVPy, as well as the large amount of ordered nitrogen atoms in C3N. The artificial synapse ensure a direct imitation of short-term and long-term plasticity in biological synapses including excitatory post-synaptic current (EPSC), paired-pulse facilitation (PPF), paired-pulse depression (PPD), PPF following PPD and post-tetanic potentiation (PTP). The C3N/PVPy matrix-based memristor which can mimic the synapse cleft based on proton conducting mechanism may find further applications in artificial intelligence.

Emulating dynamic synaptic plasticity over broad timescales with memristive device

Memristive devices have shown great potential in realizing artificial synapses efficiently for neuromorphic computing. However, emulation of various subtle forms of plasticity over broad timescales in a single device remains a challenge. In this paper, we designed a Ag/MgO/Pt memristive device exhibiting a volatile switching behavior and demonstrated various forms of synaptic plasticity from milliseconds to days in a single device. The volatile behaviors are owing to the formation and spontaneous rupture of silver nano-filaments with and without applying electrical stimuli. By manipulating the input voltage pulse strength, such as pulse amplitude, interval, and pulse number, several key features of biological synaptic plasticity including paired pulse facilitation, augmentation, post-tetanic potentiation, early long-term plasticity (LTP), and late-LTP were emulated. In addition, a reversible transition between short-term plasticity and LTP was also demonstrated. This work enables artificial synapses with rich plasticity in a single nano-device, providing a pathway to develop a large scale artificial neural network for brain inspired computing systems.

Activity dependent post-tetanic potentiation of starch-based biopolymer electrolyte gated oxide synaptic transistors

Recently, neuromorphic devices have attracted great attentions in the field of brain-inspired neuromorphic engineering. As an important form of short-term synaptic plasticity, post-tetanic potentiation (PTP) plays a crucial role in the formation of short-term memory in biological nervous system. Here, indium-tin-oxide synaptic transistors were proposed by using solution-processed starch-based biopolymer electrolytes as gate dielectrics, demonstrating good electrical performances at a low operation voltage of 1 V. Short-term plasticities were mimicked on the proposed oxide synaptic transistors. PTP behaviors were demonstrated on the synaptic devices. Furthermore, effects of prior history of synaptic activity on PTP responses have been discussed in detail. The proposed synaptic transistors may have potential applications in neuromorphic system.

Artificial Synapse Emulated by Charge Trapping‐Based Resistive Switching Device

AbstractThe traditional Von Neumann architecture‐based computers are considered to be inadequate in the coming artificial intelligence era due to increasing computation complexity and rising power consumption. Neuromorphic computing may be the key role to emulate the human brain functions and eliminate the Von Neumann bottleneck. As a basic unit in the nervous system, a synapse is responsible for transmitting information between neurons. Resistive random access memory (RRAM) is able to imitate the synaptic functions because of its tunable resistive switching behavior. Here, an artificial synapse based on solution processed polyvinylpyrrolidone (PVPy)–Au nanoparticle (NP) hybrid is fabricated, various synaptic functions including paired‐pulse facilitation (PPF), posttetanic potentiation (PTP), transformation from short‐term plasticity (STP) to long‐term plasticity (LTP) and learning‐forgetting‐relearning process are emulated, making the polymer–metal NPs hybrid system valuable candidates for the design of novel artificial neural architectures.

Prion acute synaptotoxicity is largely driven by protease-resistant PrPSc species.

Although misfolding of normal prion protein (PrPC) into abnormal conformers (PrPSc) is critical for prion disease pathogenesis our current understanding of the underlying molecular pathophysiology is rudimentary. Exploiting an electrophysiology paradigm, herein we report that at least modestly proteinase K (PK)-resistant PrPSc (PrPres) species are acutely synaptotoxic. Brief exposure to ex vivo PrPSc from two mouse-adapted prion strains (M1000 and MU02) prepared as crude brain homogenates (cM1000 and cMU02) and cell lysates from chronically M1000-infected RK13 cells (MoRK13-Inf) caused significant impairment of hippocampal CA1 region long-term potentiation (LTP), with the LTP disruption approximating that reported during the evolution of murine prion disease. Proof of PrPSc (especially PrPres) species as the synaptotoxic agent was demonstrated by: significant rescue of LTP following selective immuno-depletion of total PrP from cM1000 (dM1000); modestly PK-treated cM1000 (PK+M1000) retaining full synaptotoxicity; and restoration of the LTP impairment when employing reconstituted, PK-eluted, immuno-precipitated M1000 preparations (PK+IP-M1000). Additional detailed electrophysiological analyses exemplified by impairment of post-tetanic potentiation (PTP) suggest possible heightened pre-synaptic vulnerability to the acute synaptotoxicity. This dysfunction correlated with cumulative insufficiency of replenishment of the readily releasable pool (RRP) of vesicles during repeated high-frequency stimulation utilised for induction of LTP. Broadly comparable results with LTP and PTP impairment were obtained utilizing hippocampal slices from PrPC knockout (PrPo/o) mice, with cM1000 serial dilution assessments revealing similar sensitivity of PrPo/o and wild type (WT) slices. Size fractionation chromatography demonstrated that synaptotoxic PrP correlated with PK-resistant species >100kDa, consistent with multimeric PrPSc, with levels of these species >6 ng/ml appearing sufficient to induce synaptic dysfunction. Biochemical analyses of hippocampal slices manifesting acute synaptotoxicity demonstrated reduced levels of multiple key synaptic proteins, albeit with noteworthy differences in PrPo/o slices, while such changes were absent in hippocampi demonstrating rescued LTP through treatment with dM1000. Our findings offer important new mechanistic insights into the synaptic impairment underlying prion disease, enhancing prospects for development of targeted effective therapies.

Synaptic Plasticity and Metaplasticity of Biological Synapse Realized in a KNbO3 Memristor for Application to Artificial Synapse.

Amorphous KNbO3 (KN) films were grown on a TiN/SiO2/Si substrate to synthesize a KN memristor as a potential artificial synapse. The Pt/KN/TiN memristor exhibited typical and reliable bipolar switching behavior with multiple resistance levels. It also showed the transmission properties of a biological synapse, with a good conductance modulation linearity. Moreover, the KN memristor can emulate various biological synaptic plasticity characteristics including short-term plasticity, long-term plasticity, spike-rate dependent plasticity, paired-pulse facilitation, and post-tetanic potentiation by controlling the number and rate of the potentiation spike. Spike-timing-dependent plasticity (STDP), which is an essential property of biological synapses, is also realized in the KN memristor. The synaptic plasticity of the KN memristor can be explained by oxygen vacancy movement and oxygen vacancy filaments. The metaplasticity of biological synapses was also implemented in the KN memristor, including the metaplasticity of long-term potentiation and depression, and of STDP. Therefore, the KN memristor could be used as an artificial synapse in neuromorphic computing systems.