Synaptic Potentiation Research Articles

Mitochondrial ROS as a regulator of synaptic function.

Exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a well-studied hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis. Outside of the context of disease, the potential role of mitochondrial ROS in presynaptic function and plasticity remains largely understudied. Here, we investigated this potential role by combining electrophysiological recordings, confocal imaging, immunohistochemical staining, and optogenetics using a well-established protocol for induction and measurement of synaptic potentiation in drosophila neuromuscular preparations. We have previously found that optogenetic induction of ROS emission from presynaptic mitochondria expressing mito-killer red was accompanied by an increase in spontaneous mini junction potentials. The increase in electrical activity did not appear to be associated with major synaptic structure alterations such as the formation of presynaptic filopodia or the growth of ghost boutons. However, in existing boutons, we observed an increase in active zone markers such as nc82/Brp. We have not detected Wnt1/Wg release from synaptic boutons suggesting the involvement of other signaling pathways that underlie observed changes in electrophysiological activity mediated by ROS emission. Future studies will further inquire the role of mitochondrial ROS in synaptic potentiation, as well as the potential signaling targets of mitochondrial ROS in the presynaptic structure.

The plasticity of synaptic memristor based on 2D-MoS2 thin film prepared in large-scale by a PLD-assisted CVD method

Two-dimensional MoS2 film was directly grown via a two-step chemical vapour deposition (CVD) method in a large-scale on a phosphorus doped silicon substrate, where a precursor of Mo was Pre-deposited by pulsed laser deposition (PLD) to ensure the homogeneity of Mo source. The film was confirmed to be dense, uniform and continuous nanocrystalline of MoS2 by the characterization of XRD, Raman, SEM, TEM and XPS. Then MoS2 film was employed as the channel materials to fabricate the memristor with lateral structure of Cu/MoS2/Cu. Consequently, the devices show stable nonvolatile resistance switching characteristics, such as low operating voltages, repeated cyclic sweeps (600 times) without decrease and long retention time (>104 s). Such mechanism of resistive switching can be attributable to the space-charge limited conduction dominated by defects. Importantly, a variety of biological synaptic functions, such as synaptic potentiation, depression and repetitive learning processes, are effectively simulated. Furthermore, the relationships between the resistance state and the parameters of pulse sequence were explored based on MoS2 thin film memristors. This research provides a feasible method for manufacturing MoS2 based on memristor, which is used for information and computing applications in neural morphological devices.

Fast and Sustained Axonal Growth by BDNF Released from Chitosan Microspheres.

Brain-derived neurotrophic factor (BDNF) regulates dendritic branching and dendritic spine morphology, as well as synaptic plasticity and long-term potentiation. Consequently, BDNF deficiency has been associated with some neurological disorders such as Alzheimer's, Parkinson's or Huntington's diseases. In contrast, elevated BDNF levels correlate with recovery after traumatic central nervous system (CNS) injuries. The utility of BDNF as a therapeutic agent is limited by its short half-life in a pathological microenvironment and its low efficacy caused by unwanted consumption of non-neuronal cells or inappropriate dosing. Here, we tested the activity of chitosan microsphere-encapsulated BDNF to prevent clearance and prolong the efficacy of this neurotrophin. Neuritic growth activity of BDNF release from chitosan microspheres was observed in the PC12 rat pheochromocytoma cell line, which is dependent on neurotrophins to differentiate via the neurotrophin receptor (NTR). We obtained a rapid and sustained increase in neuritic out-growth of cells treated with BDNF-loaded chitosan microspheres over control cells (p < 0.001). The average of neuritic out-growth velocity was three times higher in the BDNF-loaded chitosan microspheres than in the free BDNF. We conclude that the slow release of BDNF from chitosan microspheres enhances signaling through NTR and promotes axonal growth in neurons, which could constitute an important therapeutic agent in neurodegenerative diseases and CNS lesions.

The beneficial effect on cognition of noninvasive brain stimulation intervention in patients with dementia: a network meta-analysis of randomized controlled trials

BackgroundDementia [i.e., Alzheimer disease (AD)], the most common neurodegenerative disease, causes profound negative impacts on executive function and quality of life. Available pharmacological treatments often fail to achieve satisfactory outcomes. Noninvasive brain stimulation (NIBS) techniques, which focally modify cortical function and enhance synaptic long-term potentiation, are potentially beneficial for the cognition in patients with AD. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and safety of different NIBS interventions in patients with AD through NMA.MethodsOnly randomized controlled trials (RCTs) examining NIBS interventions in patients with AD had been included. All NMA procedures were performed under the frequentist model. The primary and secondary outcomes were changes in cognitive function and quality of life, respectively.ResultsNineteen RCTs (639 participants) were included. The mean treatment and follow-up durations were 5.7 and 10.5 weeks, respectively. The combination of cathodal tDCS of the left dorsolateral prefrontal cortex and anodal tDCS over the right supraorbital region (c-tDCS-F3 + a-tDCS-Fp2) was associated with a significant beneficial effect on cognition compared with sham controls (standardized mean difference=2.43, 95% confidence interval=0.61–4.26, n=12 and 11). It was also associated with the greatest beneficial effect on cognition among all the investigated NIBS approaches. All the methods were well tolerated with regard to the safety profile, as reflected in the rates of adverse events or local discomfort, as well as acceptability, as indicated by dropout rate.ConclusionsThe present findings provide evidence of the benefits of NIBS, especially tDCS, for beneficial effect on cognition in patients with AD. However, because of few studies included, this effect was not replicated yet in the other studies. Therefore, future larger-scale and longer follow-up duration RCTs should be warranted.Trial registrationPROSPERO CRD42020209516. The current study had been approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).

Mechanisms That Underlie Expression of Estradiol-Induced Excitatory Synaptic Potentiation in the Hippocampus Differ between Males and Females.

17β-estradiol (E2) is synthesized in the hippocampus of both sexes and acutely potentiates excitatory synapses in each sex. Previously, we found that the mechanisms for initiation of E2-induced synaptic potentiation differ between males and females, including in the molecular signaling involved. Here, we used electrical stimulation and two-photon glutamate uncaging in hippocampal slices from adult male and female rats to investigate whether the downstream consequences of distinct molecular signaling remain different between the sexes or converge to the same mechanism(s) of expression of potentiation. This showed that synaptic activity is necessary for expression of E2-induced potentiation in females but not males, which paralleled a sex-specific requirement in females for calcium-permeable AMPARs (cpAMPARs) to stabilize potentiation. Nonstationary fluctuation analysis of two-photon evoked unitary synaptic currents showed that the postsynaptic component of E2-induced potentiation occurs either through an increase in AMPAR conductance or in nonconductive properties of AMPARs (number of channels × open probability) and never both at the same synapse. In females, most synapses (76%) were potentiated via increased AMPAR conductance, whereas in males, more synapses (60%) were potentiated via an increase in nonconductive AMPAR properties. Inhibition of cpAMPARs eliminated E2-induced synaptic potentiation in females, whereas some synapses in males were unaffected by cpAMPAR inhibition; these synapses in males potentiated exclusively via increased AMPAR nonconductive properties. This sex bias in expression mechanisms of E2-induced synaptic potentiation underscores the concept of latent sex differences in mechanisms of synaptic plasticity in which the same outcome in each sex is achieved through distinct underlying mechanisms.SIGNIFICANCE STATEMENT Estrogens are synthesized in the brains of both sexes and potentiate excitatory synapses to the same degree in each sex. Despite this apparent similarity, the molecular signaling that initiates estrogen-induced synaptic potentiation differs between the sexes. Here we show that these differences extend to the mechanisms of expression of synaptic potentiation and result in distinct patterns of postsynaptic neurotransmitter receptor modulation in each sex. Such latent sex differences, in which the same outcome is achieved through distinct underlying mechanisms in males versus females, indicate that molecular mechanisms targeted for drug development may differ between the sexes even in the absence of an overt sex difference in behavior or disease.

The Impact of Trap-Assisted Tunneling and Poole–Frenkel Emission on Synaptic Potentiation in an α-Fe2O3/p-Si Memristive Device

A signature of synaptic potentiation conductance has been observed in an α-Fe2O3/p-Si device fabricated using spin coating. The conductance of the device in dark conditions and illumination with a white light source was characterized as a function of the application of a periodic bias (voltage) with a triangular profile. The conductance of the device increases with the number of voltage cycles applied and plateaus to its maximum value of 0.70 μS under dark conditions and 12.00 μS under illumination, and this mimics the analog synaptic weight change with the action potential of a neuron. In the range of applied voltage from 0 V to 0.7 V, the conduction mechanism corresponds to trap-assisted tunneling (TAT) and in the range of 0.7–5 V it corresponds to the Poole–Frenkel emission (PFE). The conductance as a function of electrical pulses was fitted with a Hill function, which is a measure of cooperation in biological systems. In this case, it allows one to determine the turn-on threshold (K) of the device in terms of the number of voltage pulses, which are found to be 3 and 166 under dark and illumination conditions, respectively. The gradual conductance change and activation after a certain number of pulses perfectly mimics the synaptic potentiation of neurons. In addition, the threshold parameter extracted from the Hill equation fit, acting as the number of pulses for synaptic activation, is found to have programmability with the intensity of the light illumination.

The Influence of the Number of Spiking Neurons on Synaptic Plasticity.

The main advantages of spiking neural networks are the high biological plausibility and their fast response due to spiking behaviour. The response time decreases significantly in the hardware implementation of SNN because the neurons operate in parallel. Compared with the traditional computational neural network, the SNN use a lower number of neurons, which also reduces their cost. Another critical characteristic of SNN is their ability to learn by event association that is determined mainly by postsynaptic mechanisms such as long-term potentiation. However, in some conditions, presynaptic plasticity determined by post-tetanic potentiation occurs due to the fast activation of presynaptic neurons. This violates the Hebbian learning rules that are specific to postsynaptic plasticity. Hebbian learning improves the SNN ability to discriminate the neural paths trained by the temporal association of events, which is the key element of learning in the brain. This paper quantifies the efficiency of Hebbian learning as the ratio between the LTP and PTP effects on the synaptic weights. On the basis of this new idea, this work evaluates for the first time the influence of the number of neurons on the PTP/LTP ratio and consequently on the Hebbian learning efficiency. The evaluation was performed by simulating a neuron model that was successfully tested in control applications. The results show that the firing rate of postsynaptic neurons post depends on the number of presynaptic neurons pre, which increases the effect of LTP on the synaptic potentiation. When post activates at a requested rate, the learning efficiency varies in the opposite direction with the number of pres, reaching its maximum when fewer than two pres are used. In addition, Hebbian learning is more efficient at lower presynaptic firing rates that are divisors of the target frequency of post. This study concluded that, when the electronic neurons additionally model presynaptic plasticity to LTP, the efficiency of Hebbian learning is higher when fewer neurons are used. This result strengthens the observations of our previous research where the SNN with a reduced number of neurons could successfully learn to control the motion of robotic fingers.

The role of post-translational modifications in synaptic AMPA receptor activity.

AMPA-type receptors for the neurotransmitter glutamate are very dynamic entities, and changes in their synaptic abundance underlie different forms of synaptic plasticity, including long-term synaptic potentiation (LTP), long-term depression (LTD) and homeostatic scaling. The different AMPA receptor subunits (GluA1-GluA4) share a common modular structure and membrane topology, and their intracellular C-terminus tail is responsible for the interaction with intracellular proteins important in receptor trafficking. The latter sequence differs between subunits and contains most sites for post-translational modifications of the receptors, including phosphorylation, O-GlcNAcylation, ubiquitination, acetylation, palmitoylation and nitrosylation, which affect differentially the various subunits. Considering that each single subunit may undergo modifications in multiple sites, and that AMPA receptors may be formed by the assembly of different subunits, this creates multiple layers of regulation of the receptors with impact in synaptic function and plasticity. This review discusses the diversity of mechanisms involved in the post-translational modification of AMPA receptor subunits, and their impact on the subcellular distribution and synaptic activity of the receptors.

NMDA Receptor Activation-Dependent Antidepressant-Relevant Behavioral and Synaptic Actions of Ketamine.

Ketamine is a well-characterized NMDA receptor (NMDAR) antagonist, although the relevance of this pharmacology to its rapid (within hours of administration) antidepressant actions, which depend on mechanisms convergent with strengthening of excitatory synapses, is unclear. Activation of synaptic NMDARs is necessary for the induction of canonical long-term potentiation (LTP) leading to a sustained expression of increased synaptic strength. We tested the hypothesis that induction of rapid antidepressant effects requires NMDAR activation, by using behavioral pharmacology, western blot quantification of hippocampal synaptoneurosomal protein levels, and ex vivo hippocampal slice electrophysiology in male mice. We found that ketamine exerts an inverted U-shaped dose-response in antidepressant-sensitive behavioral tests, suggesting that an excessive NMDAR inhibition can prevent ketamine's antidepressant effects. Ketamine's actions to induce antidepressant-like behavioral effects, up-regulation of hippocampal AMPAR subunits GluA1 and GluA2, as well as metaplasticity measured ex vivo using electrically-stimulated LTP, were abolished by pretreatment with other non-antidepressant NMDAR antagonists, including MK-801 and CPP. Similarly, the antidepressant-like actions of other putative rapid-acting antidepressant drugs (2R,6R)-hydroxynorketamine (ketamine metabolite), MRK-016 (GABAAα5 negative allosteric modulator), and LY341495 (mGlu2/3 receptor antagonist) were blocked by NMDAR inhibition. Ketamine acted synergistically with an NMDAR positive allosteric modulator to exert antidepressant-like behavioral effects and activation of the NMDAR subunit GluN2A was necessary and sufficient for such relevant effects. We conclude rapid-acting antidepressant compounds share a common downstream NMDAR-activation dependent effector mechanism, despite variation in initial pharmacological targets. Promoting NMDAR signaling or other approaches that enhance NMDAR-dependent LTP-like synaptic potentiation may be an effective antidepressant strategy.SIGNIFICANCE STATEMENT The anesthetic and antidepressant drug ketamine is well-characterized as an NMDA receptor (NMDAR) antagonist; though, the relevance and full impact of this pharmacology to its antidepressant actions is unclear. We found that NMDAR activation, which occurs downstream of their initial actions, is necessary for the beneficial effects of ketamine and several other putative antidepressant compounds. As such, promoting NMDAR signaling, or other approaches that enhance NMDAR-dependent long-term potentiation (LTP)-like synaptic potentiation in vivo may be an effective antidepressant strategy directly, or acting synergistically with other drug or interventional treatments.

Forming-free plant resistive random access memory based on the Coulomb blockade effect produced by gold nanoparticles.

Resistive random access memory has been widely studied as a powerful candidate for building future memories and realizing high-efficiency artificial neuromorphic systems. In this paper, gold nanoparticles (Au NPs) are doped in a leaf solution of Scindapsus aureus (SA) as the active layer to fabricate Al/SA:Au NPs/ITO/glass resistive random access memory. The device exhibits stable bipolar resistance switching characteristics. More importantly, the device's multilevel storage capabilities and synaptic potentiation and depression behaviour have been proven. Compared with the device without doped Au NPs in the active layer, the device has a higher ON/OFF current ratio, which is attributed to the Coulomb blockade effect caused by the Au NPs. The device plays an important role in realizing high-density memory and efficient artificial neuromorphic systems.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

E-Syt1 Regulates Neuronal Activity-Dependent Endoplasmic Reticulum-Plasma Membrane Junctions and Surface Expression of AMPA Receptors.

Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites/junctions play important roles in cell physiology including signal transduction, ion and lipid transfer, and membrane dynamics. However, little is known about the dynamic regulation and functional roles of ER-PM junctions in neurons. Using a split green fluorescent protein-based membrane contact probe, we find that the density of ER-PM contact sites changes dynamically in the dendrites of hippocampal neurons undergoing long-term synaptic potentiation (LTP). We show that the Ca2±-sensing membrane tethering protein Extended Synaptotagmin 1 (E-Syt1) mediates the formation of ER-PM contact sites during LTP. We also show that E-Syt1 is required for neuronal activity-dependent surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors. These findings implicate ER-PM junctions in the regulation of neurotransmitter receptor trafficking and synaptic plasticity.

Remembering and forgetting in sleep: Selective synaptic plasticity during sleep driven by scaling factors Homer1a and Arc

Sleep is a conserved and essential process that supports learning and memory. Synapses are a major target of sleep function and a locus of sleep need. Evidence in the literature suggests that the need for sleep has a cellular or microcircuit level basis, and that sleep need can accumulate within localized brain regions as a function of waking activity. Activation of sleep promoting kinases and accumulation of synaptic phosphorylation was recently shown to be part of the molecular basis for the localized sleep need. A prominent hypothesis in the field suggests that some benefits of sleep are mediated by a broad but selective weakening, or scaling-down, of synaptic strength during sleep in order to offset increased excitability from synaptic potentiation during wake. The literature also shows that synapses can be strengthened during sleep, raising the question of what molecular mechanisms may allow for selection of synaptic plasticity types during sleep. Here I describe mechanisms of action of the scaling factors Arc and Homer1a in selective plasticity and links with sleep need. Arc and Homer1a are induced in neurons in response to waking neuronal activity and accumulate with time spent awake. I suggest that during sleep, Arc and Homer1a drive broad weakening of synapses through homeostatic scaling-down, but in a manner that is sensitive to the plasticity history of individual synapses, based on patterned phosphorylation of synaptic proteins. Therefore, Arc and Homer1a may offer insights into the intricate links between a cellular basis of sleep need and memory consolidation during sleep.

Adolescent morphine exposure impairs dark avoidance memory and synaptic potentiation of ventral hippocampal CA1 during adulthood in rats

Adolescence is a neurobiological critical period for neurodevelopmental processes. Adolescent opioid exposure can affect cognitive abilities via regional-specific lasting changes in brain structure and function. The current study was therefore designed to assess the long-term effects of adolescent morphine exposure on dark avoidance memory and synaptic plasticity of the ventral hippocampal CA1.Adolescent Wistar rats received escalating doses of morphine for 10 days. Morphine injections were started with an incremental dose of 2.5 mg/kg to reach a dose of 25 mg/kg. 30 days after the last injection, inhibitory memory and in vitro field potential recording were evaluated. Also, the weight of the animals was measured during drug and post-drug exposure.We found that adolescent morphine exposure decreased weight gain during morphine and post-morphine exposure. Passive avoidance memory was impaired in the morphine group. Moreover, adolescent morphine exposure caused an increase in baseline synaptic responsiveness and failed long-term potentiation (LTP) in the ventral hippocampal CA1 during adulthood. In the morphine group, the mean values of the field excitatory postsynaptic potential (fEPSP) slopes required to elicit a half-maximal population spike (PS) amplitude were significantly greater than that of the saline group. Therefore, adolescent morphine exposure has a durable effect on memory functions, synaptic activity, and plasticity of ventral hippocampal CA1.Adults with adolescent morphine exposures may experience maladaptive behaviors and cognitive disabilities.

Sleep slow-wave oscillations trigger seizures in a genetic epilepsy model of Dravet syndrome.

Sleep is the preferential period when epileptic spike-wave discharges appear in human epileptic patients, including genetic epileptic seizures such as Dravet syndrome with multiple mutations including SCN1A mutation and GABAA receptor γ2 subunit Gabrg2Q390X mutation in patients, which presents more severe epileptic symptoms in female patients than male patients. However, the seizure onset mechanism during sleep still remains unknown. Our previous work has shown that the sleep-like state-dependent homeostatic synaptic potentiation can trigger epileptic spike-wave discharges in one transgenic heterozygous Gabrg2+/Q390X knock-in mouse model.1 Here, using this heterozygous knock-in mouse model, we hypothesized that slow-wave oscillations themselves in vivo could trigger epileptic seizures. We found that epileptic spike-wave discharges in heterozygous Gabrg2+/Q390X knock-in mice exhibited preferential incidence during non-rapid eye movement sleep period, accompanied by motor immobility/facial myoclonus/vibrissal twitching and more frequent spike-wave discharge incidence appeared in female heterozygous knock-in mice than male heterozygous knock-in mice. Optogenetically induced slow-wave oscillations in vivo significantly increased epileptic spike-wave discharge incidence in heterozygous Gabrg2+/Q390X knock-in mice with longer duration of non-rapid eye movement sleep or quiet-wakeful states. Furthermore, suppression of slow-wave oscillation-related homeostatic synaptic potentiation by 4-(diethylamino)-benzaldehyde injection (i.p.) greatly attenuated spike-wave discharge incidence in heterozygous knock-in mice, suggesting that slow-wave oscillations in vivo did trigger seizure activity in heterozygous knock-in mice. Meanwhile, sleep spindle generation in wild-type littermates and heterozygous Gabrg2+/Q390X knock-in mice involved the slow-wave oscillation-related homeostatic synaptic potentiation that also contributed to epileptic spike-wave discharge generation in heterozygous Gabrg2+/Q390X knock-in mice. In addition, EEG spectral power of delta frequency (0.1-4 Hz) during non-rapid eye movement sleep was significantly larger in female heterozygous Gabrg2+/Q390X knock-in mice than that in male heterozygous Gabrg2+/Q390X knock-in mice, which likely contributes to the gender difference in seizure incidence during non-rapid eye movement sleep/quiet-wake states of human patients. Overall, all these results indicate that slow-wave oscillations in vivo trigger the seizure onset in heterozygous Gabrg2+/Q390X knock-in mice, preferentially during non-rapid eye movement sleep period and likely generate the sex difference in seizure incidence between male and female heterozygous Gabrg2+/Q390X knock-in mice.

Subclinical β‐amyloid peptides impair homeostatic synaptic potentiation in hippocampal neurons in 5XFAD mice

AbstractBackgroundAlzheimer’s disease (AD) patients exhibit early symptoms of non‐rapid eye movement sleep (NREM) reduction and relatively REM sleep increase, which influences homeostatic synaptic plasticity (HSP) in cortical and subcortical neurons. Meanwhile, β‐amyloid peptides can suppress synaptic plasticity in hippocampus to impair learning/memory in animal studies.MethodIn accordance with IACUC of Vanderbilt University Medical center, coronal brain slices were prepared from wt and hemi 5xFAD mice at postnatal days (P)30, 60‐90 and 120‐150. Whole‐cell patch‐clamp recordings were made from hippocampal CA1 pyramidal neurons to record spontaneous excitatory synaptic currents (sEPSCs) at 32°C (clamped at ‐55.8mV, chloride reversal potentials). Slow‐wave oscillations (SWOs, 0.5 Hz, 10 min) were induced by injecting sinusoidal currents into neurons to simulate neuronal activity (up/down state) during NREM sleep. 200 µM β‐amyloid peptides were used in ACSF for this study.ResultCompared with age‐matched wt littermates at P30 and P60‐90, sEPSCs in hippocampal neurons from hemi 5xFAD mice (n = 4 mice) exhibited larger amplitudes and higher frequency. However, at P120‐150, sEPSCs in neurons from hemi 5xFAD mice (n = 5 mice) became smaller than wt littermates (n = 4 mice), suggesting that excitatory synapses in hemi 5xFAD mice may be altered along the ageing course. Moreover, following SWO induction, HSP could be induced in neurons from wt littermates at all postnatal ages (n = 5 mice) and post‐SWO sEPSCs in neurons were increased. However, HSP could not be induced in neurons from hemi 5xFAD mice at P120‐150, except P30 and P60‐90. Moreover, 200 µM β‐amyloid peptides can suppress this synaptic potentiation in neurons from hemi 5XFAD mice at P90 (n = 4 mice).ConclusionReduced NREM sleep activity in hemi 5xFAD mice can impair sEPSCs and HSP in hippocampal CA1 neurons along the ageing course, and subclinical β‐amyloid peptides can suppress this sleep‐related homeostatic synaptic potentiation, which contributes to cognitive deficits in AD patients.

Ginsenoside-Rg1 mitigates cardiac arrest-induced cognitive damage by modulating neuroinflammation and hippocampal plasticity

Ginsenoside-Rg1 can effectively ameliorate mental disorders, but whether ginsenoside-Rg1 plays a neuroprotective role in cardiac arrest and cardiopulmonary resuscitation (CA/CPR)-induced cognitive impairment remains unclear. In this study, a 5-min asphyxia-based CA/CPR rat model was established to explore the mechanisms underlying the effects of ginsenoside-Rg1 (40 mg·kg-1·d-1, ip, 14 days) on its cognitive alterations. These CA/CPR rats displayed spatial learning and memory impairment in the Morris water maze, as reflected in the compromised basal synaptic transmission and long-term potentiation (LTP) at the Schaffer collateral of hippocampal CA1 area in vivo electrophysiology, whereas the ginsenoside-Rg1 remarkably mitigated these alterations. Next, we found that ginsenoside-Rg1 inhibited hippocampal neuroinflammation by alleviating the CA/CPR-induced hippocampal activation of microglia and astrocytes and the overexpression of related proinflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α). In addition, ginsenoside-Rg1 improved CA/CPR-induced hippocampal neuronal apoptosis, dendritic spines and synaptic ultrastructure defects as associated with the upregulation of the key synaptic regulatory proteins. Furthermore, ginsenoside-Rg1 could ameliorate CA/CPR-induced aberrant expression of the key regulators of hippocampal glutamate signaling pathways, excitatory amino acid transporter 2 (EAAT2), excitatory amino acid transporter 1 (EAAT1), Glutamine Synthetase (GS), GluN2B, and glutamate. In conclusion, ginsenoside-Rg1 exerts its neuroprotective effects by ameliorating hippocampus-dependent neuroglia activation-mediated neuroinflammation and neuroplasticity deficits, shedding new light on the therapeutic intervention of CA/CPR-related cognitive disorders.

Using Hebbian Learning for Training Spiking Neural Networks to Control Fingers of Robotic Hands

Adaptability is one of the main characteristics of the bio-inspired control units for the anthropomorphic robotic hands. This characteristic provides the artificial hands with the ability to learn new motions and to improve the accuracy of the known ones. This paper presents a method to train spiking neural networks (SNNs) to control anthropomorphic fingers using proprioceptive sensors and Hebbian learning. Being inspired from physical guidance (PG), the proposed method eliminates the need for complex processing of the natural hand motions. To validate the proposed concept we implemented an electronic SNN that learns to control using the output of neuromorphic flexion and force sensors, two opposing actuated fingers actuated by shape memory alloys. Learning occurs when the untrained neural paths triggered by a command signal activate concurrently with the sensor specific neural paths that drive the motion detected by the flexion sensors. The results show that a SNN with a few neurons connects by synaptic potentiation the input neurons activated by the command signal to the output neurons which are activated during the passive finger motions. This mechanism is validated for grasping when the SNN is trained to flex simultaneously the index and thumb fingers if a push button is pressed. The proposed concept is suitable for implementing the neural control units of anthropomorphic robots which are able to learn motions by PG with proper sensors configuration.

Conducting ferroelectric domain walls emulating aspects of neurological behavior

The electrical conductivity of lithium niobate thin film capacitor structures depends on the density of conducting 180° domain walls, which traverse the interelectrode gap, and on their inclination angle with respect to the polarization axis. Both microstructural characteristics can be altered by applying electric fields, but changes are time-dependent and relax, upon field removal, into a diverse range of remanent states. As a result, the measured conductance is a complex history-dependent function of electric field and time. Here, we show that complexity in the kinetics of microstructural change, in this ferroelectric system, can generate transport behavior that is strongly reminiscent of that seen in key neurological building blocks, such as synapses. Successive voltage pulses, of positive and negative polarity, progressively enhance or suppress domain wall related conductance (analogous to synaptic potentiation and depression), in a way that depends on both the pulse voltage magnitude and frequency. Synaptic spike-rate-dependent plasticity and even Ebbinghaus forgetting behavior, characteristic of learning and memory in the brain, can be emulated as a result. Conductance can also be changed according to the time difference between designed identical voltage pulse waveforms, applied to top and bottom contact electrodes, in a way that can mimic both Hebbian and anti-Hebbian spike-timing-dependent plasticity in synapses. While such features have been seen in, and developed for, other kinds of memristors, few have previously been realized through the manipulation of conducting ferroelectric domain walls.

A hybrid memristor with oxide-polymer heterojunction

A hybrid memristor based on the bilayer structure of indium gallium zinc oxide (IGZO)/polyvinyl alcohol (PVA) is developed, which demonstrates device state updates in an analog manner with high reliability. The IGZO/PVA heterojunction is crucial for the realization of the memristive characteristics, presumably associated with oxygen ion redistribution across the IGZO/PVA interface. The hybrid memristor may act as an electronic synapse, being capable of emulating synaptic potentiation with good linearity, synaptic depression, and paired-pulse facilitation. It highlights potential applications of the oxide-polymer heterojunction in the exploration of neuromorphic devices.