Li-Ion Doped Artificial Synaptic Memristor for Highly Linear Neuromorphic Computing

Neuromorphic computing, an innovative technology inspired by the human brain, has attracted increasing attention as a promising technology for the development of artificial intelligence systems. This study proposes synaptic transistors with a Li1-xAlxTi2-x(PO4)3 (LATP) layer to analyze the conductance modulation linearity, which is essential for weight mapping and updating during on-chip learning processes. The high ionic conductivity of the LATP electrolyte provides a large hysteresis window and enables linear weight update in synaptic devices. The results demonstrate that optimizing the LATP layer thickness improves the conductance modulation and linearity of synaptic transistors during potentiation and degradation. A 20 nm-thick LATP layer results in the most nonlinear depression (αd = -6.59), whereas a 100 nm-thick LATP layer results in the smallest nonlinearity (αd = -2.22). Additionally, a device with the optimal 100 nm-thick LATP layer exhibits the highest average recognition accuracy of 94.8% and the smallest fluctuation, indicating that the linearity characteristics of a device play a crucial role in weight update during learning and can significantly affect the recognition accuracy.

Engineering of TiN/ZnO/SnO2/ZnO/Pt multilayer memristor with advanced electronic synapses and analog switching for neuromorphic computing

Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

Storage or processing of information underlies a mechanism able to change the efficacy of certain synapses depending on its activity. Long-term potentiation (LTP) and long-term depression (LTD) are two types of experimentally induced activity dependent change in synaptic efficacy (plasticity). The aim of this study was to determine the subtype specific involvement of group I metabotropic glutamate receptors (mGlus) in both forms of synaptic plasticity, namely LTP and LTD. The mGlu activation underlying pathological processes was also investigated. For all investigations, rats were chronically implanted with recording and stimulating electrodes to enable measurement of evoked potentials from medial perforant path -- dentate gyrus granule cell synapses. An injection cannula was inserted into the ipsilateral cerebral ventricle to enable drug application. Experiments were begun 10d subsequent to the implantation procedure. Histological investigations of hippocampal tissue was used to determine possible changes in cell viability after the induction of chemical LTD. Robust LTP which lasted for over 25h was generated using 200Hz tetanisation (HFT), whereas robust LTD was induced either by 1Hz low-frequency stimulation (LFS) or by pharmacological mGlu activation. The potent mGlu5 receptor agonist MPEP (2-methyl-6-(phenylethynyl)pyridine), applied in concentrations which did not affect basal synaptic transmission, dose-dependently impaired the induction and expression of LTP. Application of MPEP 5 min after tetanisation inhibited late LTP (> 24h). Injections of the potent mGlu1 agonist LY367385 ((S)-(+)-α-Amino-4-carboxy-2-methylbenzenacetic acid), in the concentrations investigated, did not effect basal synaptic transmission. In contrast, a dose- dependent impairment of LTP expression was observed. The lowest concentration used, had no effect on LTP induction, whereas higher concentrations reduced both LTP induction and expression. In contrast to MPEP application, the injection of LY367385 5min after LTP induction did not effect LTP expression. The results strongly implicate an involvement of mGlu1 in LTP induction, whereas the group I mGlu subtype 5 seems to be more involved in LTP expression. Investigating the subtype specific group I mGlu involvement in LTD afford differential results. Whereas LFS-induced LTD strongly required mGlu1 activation during LFS, chemical LTD is induced by activation of mGlu5. Induction of chemical LTD with the group I mGlu receptor agonist, (RS)-3,5-Dihydroxyphenylglycine (DHPG) occluded subsequent induction of LFS- induced LTD. Application of LFS following selective pharmacological activation of mGlu5 by (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) led to de-depression. Further analysis revealed that concurrent induction of chemically-induced and LFS-induced LTD led to an increase of intracellular calcium sufficient for the induction of LTP by LFS. Whereas LFS-induced LTD required mGlu1 activation during LFS, activation of mGlu5-mediated chemical LTD did not influence responses during LFS. In a next step, it was possible to induce stable LTD by application of the potent group III mGlu agonist AP4 (L-(+)-2-Amino-4-phosphonobutyric acid). The persistent LTD induced by the group I mGlu receptor agonist, DHPG, or the group III mGlu receptor agonist, AP4 were compared. Application of the protein synthesis inhibitor Anisomycin 2h prior to DHPG-injection inhibited the expression of LTD from 6h following DHPG injection. In contrast, Anisomycin did not affect LTD induced by AP4. A paired pulse paradigm determined that AP4-LTD is presynaptic whereas DHPG-LTD has both pre-and postsynaptic components. Histological evaluation at either 4h or 7d following AP4-injection showed that AP4-mediated LTD was ... [abstract truncated]

Cannabinoids, the active constituents of marijuana, are known to impair learning and memory. Receptors for cannabinoids are highly expressed in the hippocampus, a brain region that is believed to play an important role in certain forms of learning and memory. To investigate the possible contribution of cannabinoid receptor-mediated deficits in hippocampal function to the learning and memory impairments produced by marijuana, we studied the effects of cannabinoid receptor activation on two models of learning and memory, long-term potentiation (LTP) and long-term depression (LTD), in hippocampal slices. Although LTP and LTD of CA1 field potentials were blocked by cannabinoid receptor activation in the presence of Mg(2+), they could be induced after Mg(2+) was removed. Similarly, LTP and LTD of whole-cell EPSCs were unimpaired in the presence of cannabinoid receptor agonist when the postsynaptic membrane was depolarized during the LTP or LTD induction protocol. Cannabinoid receptor activation also reduced EPSCs and enhanced paired-pulse facilitation, while having no effect on the amplitude of spontaneous miniature EPSCs. Finally, as with cannabinoid receptor activation, inhibition of LTP by adenosine receptor activation could be overcome by removal of Mg(2+) or depolarization of the postsynaptic membrane during tetanus. Our results indicate that cannabinoid receptor activation does not directly inhibit the molecular mechanisms responsible for long-term synaptic plasticity but instead impairs LTP and LTD by reducing presynaptic neurotransmitter release to a level below that required to depolarize the postsynaptic membrane to relieve Mg(2+) blockade of NMDA receptors.

Ferrimagnetic materials with antiparallel exchange coupling, exhibit spin‐orbit‐torque‐induced dynamics, offering an emerging platform for realizing neuromorphic devices, such as artificial synapses. However, the state‐of‐the‐art artificial synapses based on ferrimagnet suffer from poor analog switching linearity, which serves as a bottleneck for achieving complex tasks with high accuracy in neuromorphic computing. Here, an artificial synapse is reported with high‐weight update linearity in a compensated ferrimagnetic crossbar device. In particular, the linear weight update of the synapses is enhanced by engineering the current density distribution. Using experimentally derived device parameters, handwritten digit recognition can be achieved with an accuracy of over 95% in a three‐layer fully connected artificial neural network. The work provides a universal method to improve the synaptic linearity, which also paves the way for applying the spin‐orbit device in neuromorphic computing.

In this paper, gradual and symmetrical long-term potentiation (LTP) and long-term depression (LTD) were achieved by applying the optimal electrical pulse condition of the interfacial phase-change memory (iPCM) based on a superlattice (SL) structure fabricated by stacking GeTe/Sb2Te3 alternately to implement an artificial synapse in neuromorphic computing. Furthermore, conventional phase-change random access memory (PCRAM) based on a Ge–Sb–Te (GST) alloy with an identical bottom electrode contact size was fabricated to compare the electrical characteristics. The results showed a reduction in the reset energy consumption of the GeTe/Sb2Te3 (GT/ST) iPCM by more than 69% of the GST alloy for each bottom electrode contact size. Additionally, the GT/ST iPCM achieved gradual conductance tuning and 90.6% symmetry between LTP and LTD with a relatively unsophisticated pulse scheme. Based on the above results, GT/ST iPCM is anticipated to be exploitable as a synaptic device used for brain-inspired computing and to be utilized for next-generation non-volatile memory.

Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus

1. Extracellular bath application of the selective Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor KN-62 to hippocampal slices in vitro blocked the induction of long-term depression (LTD) by low-frequency Schaffer collateral stimulation (1 Hz/15 min) of the same concentration as has been shown previously to prevent induction of long-term potentiation (LTP) at these synapses. 2. In contrast, postsynaptic intracellular infusion of KN-62 into single CA1 pyramidal neurons did not prevent induction of LTD, although it was quite effective in blocking LTP. 3. We conclude that there is a presynaptic CaMKII that must be activated to induce LTD, whereas postsynaptic CaMKII stimulation is needed to evoke LTP. 4. Bath application of KN-62 also blocked depotentiation by low-frequency stimuli of previously induced LTP, suggesting that induction of depotentiation and de novo LTD may require the same CaMKII-dependent mechanisms.

Zinc has complex effects on NMDA receptors (NMDARs) and may be an endogenous modulator of synaptic plasticity. In the CA1 region of rat hippocampal slices, we observed that low micromolar concentrations of zinc depress NMDAR synaptic responses by 40-50% and inhibit long-term depression (LTD) but not long-term potentiation (LTP). A combination of zinc plus ifenprodil, an inhibitor of NR1/NR2B receptors, produced no greater inhibition of synaptic NMDARs than either agent alone, suggesting overlapping effects on NMDARs. Similar to low micromolar zinc, ifenprodil inhibited LTD but not LTP. In contrast, low concentrations of 2-amino-5-phosphonovalerate (APV) did not block either LTP or LTD despite producing >50% inhibition of synaptic NMDARs. NVP-AAM077 ([(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydro-quinoxalin-5-yl)-methyl]phosphonic acid), an antagonist with relative NR1/NR2A selectivity at low concentrations, also inhibited synaptic NMDARs by approximately 50% at 0.05 mum but failed to completely block either LTP or LTD. These results suggest that LTD induction depends on specific NMDARs with sensitivity to low micromolar zinc and ifenprodil, but LTP is less dependent on specific NMDAR subtypes. Because high-affinity sites of NR2A are likely occupied by ambient zinc, we also examined effects of extracellular zinc chelators. Zinc chelation blocked LTP but had no effect on LTD. This LTP inhibition was overcome by APV and NVP-AAM077 but not ifenprodil, suggesting that zinc chelation unmasks tonic NR1/NR2A activation that negatively modulates LTP.

Two opposite types of synaptic plasticity in the CA1 hippocampus, long-term potentiation (LTP) and long-term depression (LTD), require postsynaptic Ca2+ elevation. To explain these apparently contradictory phenomena, the current view assumes that a moderate postsynaptic increase in Ca2+ leads to LTD, whereas a large increase leads to LTP. No detailed study has so far been attempted to investigate whether the instantaneous Ca2+ elevation level differentially induces LTP or LTD. We therefore used low-frequency (1 Hz) stimulation of Schaffer collateral/commissural fibers in rat hippocampal slices, during a Mg2+-free period, as the conditioning stimulus to investigate this. This allowed low-frequency afferent stimulation to cause a postsynaptic Ca2+ influx because the voltage-dependent block of N-methyl-D-aspartate (NMDA) receptor-channels by Mg2+ was removed. When delivered during the Mg2+-free period, a single pulse, as well as 2-600 pulses, induced LTP that was occluded with tetanus-induced LTP. To decrease the Ca2+ influx, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were completely blocked by the addition of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to the conditioning medium, in which 1 Hz afferent stimuli (1-600 pulses) induced less LTP and never induced LTD. To further reduce the Ca2+ influx, NMDA receptors were partially blocked with D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5). A small number of 1 Hz stimuli, however, never induced LTD. Only when the conditioning stimuli exceeded 200 pulses was LTD induced. The present findings provide definitive evidence that protracted conditioning is a prerequisite for the induction of LTD. Thus, not only the amplitude but also the duration of postsynaptic Ca2+ elevation could be essential factors for differentially inducing LTP or LTD.

Neuromorphic computing, inspired by the processing capabilities of the brain, aims to overcome the limitations of conventional computing architectures. Valence change memory (VCM), along with other emerging redox-based resistive random-access memory (ReRAM) devices, is a promising candidate for this endeavor due to its features, including fast write times. Moreover, VCM devices are also suitable for neuromorphic applications, such as long-term potentiation (LTP), short-term plasticity (STP), and gradual switching. However, the evaluation of these schemes on sub-100ps timescales presents significant challenges, as the capacitive current dominates the device current, obscuring the true conductance state. Therefore, robust methods are required to analyze the current response of ReRAM cells to ultrashort pulses and varying delays, which is critical for advanced neuromorphic applications. To address the challenge of dominating capacitive current, this study proposes two methods: the integration method and the reference method. The integration method integrates the current and eliminates capacitive charges across a full charge/discharge cycle, proving to be more reliable for longer pulses and delays exceeding 200ps. On the other hand, the reference method determines the device current by subtracting the capacitive current from the measured current, using a reference measurement. This method is particularly adept at analyzing shorter pulses and delays below 200ps. These methods provide effective solutions to the challenge of capacitive current dominance to ultrashort pulses and varying delays.

In the present report, we focused our attention on the role played by the muscarinic acetylcholine receptors (mAChRs) in different forms of long-term synaptic plasticity. Specifically, we investigated long-term potentiation (LTP) and long-term depression (LTD) expression elicited by theta-burst stimulation (TBS) and low-frequency stimulation (LFS), respectively, in visual cortical slices obtained from different mAChR knockout (KO) mice. A normal LTP was evoked in M(1)/M(3) double KO mice, while LTP was impaired in the M(2)/M(4) double KO animals. On the other hand, LFS induced LTD in M(2)/M(4) double KO mice, but failed to do so in M(1)/M(3) KO mice. Interestingly, LFS produced LTP instead of LTD in M(1)/M(3) KO mice. Analysis of mAChR single KO mice revealed that LTP was affected only by the simultaneous absence of both M(2) and M(4) receptors. A LFS-dependent shift from LTD to LTP was also observed in slices from M(1) KO mice, while LTD was simply abolished in slices from M(3) KO mice. Using pharmacological tools, we showed that LTP in control mice was blocked by pertussis toxin, an inhibitor of G(i/o) proteins, but not by raising intracellular cAMP levels. In addition, the inhibition of phospholipase C by U73122 induced the same shift from LTD to LTP after LFS observed in M(1) single KO and M(1)/M(3) double KO mice. Our results indicate that different mAChR subtypes regulate different forms of long-term synaptic plasticity in the mouse visual cortex, activating specific G proteins and downstream intracellular mechanisms.

NMDA receptor antagonists block heterosynaptic long-term depression (LTD) but not long-term potentiation (LTP) in the CA3 region following lateral perforant path stimulation

Being renowned for operating with visible light pulses and electrical signals, optoelectronic memristive synaptic devices have excellent potential for neuromorphic computing systems and artificial visual information processing. Here, wepresent a flexible back-end-of-line compatible optoelectronic memristor based on solution-processable black phosphorus/HfOx bilayer with excellent synaptic features, towards biomimetic retinas. The device shows highly stable synaptic features such as long-term potentiation (LTP) and long-term depression (LTD) for repetitive 1000 epochs, having 400 conductance pulses, each. The device presents advanced synaptic features in terms of long-term memory (LTM)/short term memory (STM), as well as learning-forgetting-relearning when visible light wasinduced on it. These advanced synaptic features can improve the information processing abilities for neuromorphic applications. Interestingly, the STM can be converted into LTM by adjusting the intensity of light and illumination time. Using the light induced characteristics of the device, a 6×6 synaptic array wasdeveloped to exhibit possible use in artificial visual perception. Moreover, the devices wereflexed using a Silicon back-etching process. The resulting flexible devices demonstrate stable synaptic features when bent down to 1cm radius. These multifunctional features in a single memristive cell make it highly suitable for optoelectronic memory storage, neuromorphic computing, and artificial visual perception applications. This article is protected by copyright. All rights reserved.