Long-term Plasticity Research Articles

Donor-acceptor-type poly[chalcogenoviologen-alt-triphenylamine] for synaptic biomimicking and neuromorphic computing

SummaryPolymer memristors are preeminent candidates for low-power edge computing paradigms. Poly[chalcogenoviologen-alt-triphenylamine] (PCVTPA) has been synthesized by direct coupling of chalcogeno-viologen as electron acceptor and 4-(bromomethyl)-N-(4-(bromo-methyl)phenyl)-N-phenylaniline as electron donor. The introduction of chalcogen atoms (S, Se, Te) into viologen scaffolds can greatly improve electrical conductive, electrochemical, and electrochromic properties of the materials when compared with the conventional viologens. Taking PTeVTPA as an example, the as-fabricated electronic device with a configuration of Al/PTeVTPA/ITO exhibits excellent multilevel storage and history-dependent memristive switching performance. Associated with the unique memristive behavior, the PTeVTPA-based device can not only be used to emulate the synaptic potentiation/depression, the human's learning and memorizing functions, and the transition from short-term synaptic plasticity to long-term plasticity but also carry out decimal arithmetic operations as well. This work will be expected to offer a train of new thought for constructing high-performance synaptic biomimicking and neuromorphic computing system in the near future.

Reflections on Bharatanatyam and Neuroscience. A Dance Studies Perspective

Building on recent interest in the convergence of arts and sciences, we propose specific areas of intersection between the disciplines of Bharatanatyam, a classical Indian dance, and neuroscience. We present personal reflections by practitioners of both disciplines and propose that Bharatanatyam can be used to understand and explain brain functioning and that neuroscience can help analyze the dancing Bharatanatyam brain. We explore conceptual areas of convergence between the two fields as well as specific points of connection using language acquisition, rhythm, music, and cognition as examples. We conjecture that Bharatanatyam training and practice support long-term neuronal plasticity in various parts of the brain, including but not limited to the hippocampus, motor, premotor cortex, and the cerebellum. The beginning of the study of the intersection between these disciplines will pave the way for additional allied fields of rich thinking, exploration and potentially, therapy.

Tactile tribotronic reconfigurable p-n junctions for artificial synapses

The emulation of biological synapses with learning and memory functions and versatile plasticity is significantly promising for neuromorphic computing systems. Here, a robust and continuously adjustable mechanoplastic semifloating-gate transistor is demonstrated based on an integrated graphene/hexagonal boron nitride/tungsten diselenide van der Waals heterostructure and a triboelectric nanogenerator (TENG). The working states (p-n junction or n+-n junction) can be manipulated and switched under the sophisticated modulation of triboelectric potential derived from mechanical actions, which is attributed to carriers trapping and detrapping in the graphene layer. Furthermore, a reconfigurable artificial synapse is constructed based on such mechanoplastic transistor that can simulate typical synaptic plasticity and implement dynamic control correlations in each response mode by further designing the amplitude and duration. The artificial synapse can work with ultra-low energy consumption at 74.2 fJ per synaptic event and the extended synaptic weights. Under the synergetic effect of the semifloating gate, the synaptic device can enable successive mechanical facilitation/depression, short-/long-term plasticity and learning-experience behavior, exhibiting the mechanical behavior derived synaptic plasticity. Such reconfigurable and mechanoplastic features provide an insight into the applications of energy-efficient and real-time interactive neuromodulation in the future artificial intelligent system beyond von Neumann architecture.

Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy.

Status epilepticus (SE) causes persistent abnormalities in the functioning of neuronal networks, often resulting in worsening epileptic seizures. Many details of cellular and molecular mechanisms of seizure-induced changes are still unknown. The lithium–pilocarpine model of epilepsy in rats reproduces many features of human temporal lobe epilepsy. In this work, using the lithium–pilocarpine model in three-week-old rats, we examined the morphological and electrophysiological changes in the hippocampus within a week following pilocarpine-induced seizures. We found that almost a third of the neurons in the hippocampus and dentate gyrus died on the first day, but this was not accompanied by impaired synaptic plasticity at that time. A diminished long-term potentiation (LTP) was observed following three days, and the negative effect of SE on plasticity increased one week later, being accompanied by astrogliosis. The attenuation of LTP was caused by the weakening of N-methyl-D-aspartate receptor (NMDAR)-dependent signaling. NMDAR-current was more than two-fold weaker during high-frequency stimulation in the post-SE rats than in the control group. Application of glial transmitter D-serine, a coagonist of NMDARs, allows the enhancement of the NMDAR-dependent current and the restoration of LTP. These results suggest that the disorder of neuron–astrocyte interactions plays a critical role in the impairment of synaptic plasticity.

Site-Specific Regulated Memristors via Electron-Beam-Induced Functionalization of HfO2.

Emerging nonvolatile resistive switching, also known as the memristor, works with a distinct concept that relies mainly on the change in the composition of the active materials, rather than to store the charge. Particularly for oxide-based memristors, the switching is often governed by the random and unpredicted temporal/spatial migration of oxygen defects, resulting in possessing limitations in terms of control over conduction channel formation and inability to regulate hysteresis loop opening. Therefore, site specific dynamic control of defect concentration in the active materials can offer a unique opportunity to realize on-demand regulation of memory storage and artificial intelligence capabilities. Here, high-performance, site-specific spatially scalable memristor devices are fabricated by stabilizing the conduction channel via manipulation of oxygen defects using electron-beam irradiation. Specifically, the memristors exhibit highly stable and electron-beam dose-regulated multilevel analog hysteresis loop opening with adjustable switching ratios even higher than 104 . Additionally, broad modulation of neural activities, including short- and long-term plasticity, paired-pulse facilitation, spike-timing-dependent plasticity, and dynamic multipattern memory processing, are demonstrated. The work opens a new possibility to regulate the resistive switching behavior and control mimicking of neural activities, providing a hitherto unseen tunability in two-terminal oxide-based memristors.

The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice

Recent studies showed a possible association between perfluorooctane sulfonate (PFOS) and developmental disabilities. We previously found the specific effects of PFOS exposure on learning and memory, however, its effect on the other developmental disabilities such as motor and social deficits remains unclear. We examined the effect of early lactational PFOS exposure on motor coordination, social activity, and anxiety in male mice. We orally administered a PFOS solution to dams from postnatal day 1–14. At 10 weeks old, we conducted a behavior test battery to evaluate motor performance, social activity, and anxiety, followed by electrophysiology and Western blot analysis. PFOS-exposed mice displayed impaired motor coordination. Whole-cell patch-clamp recordings from Purkinje cells revealed that the short-term and long-term plasticity at parallel fiber-Purkinje cell synapses are affected by PFOS exposure. Western blot analysis indicated that PFOS exposure increased syntaxin binding protein 1 (Munc18-1) and glutamate metabotropic receptor 1 (mGluR1) protein levels, which may be associated with the change in neurotransmitter release from parallel fibers and the level of long-term depression, respectively. The present study demonstrates that lactational PFOS exposure may have disrupted the pre- and postsynaptic plasticity at parallel fiber-Purkinje cell synapses, causing profound, long-lasting abnormal effects on the cerebellar function.

Computational epidemiology study of homeostatic compensation during sensorimotor aging

The vestibulo-ocular reflex (VOR) stabilizes vision during head motion. Age-related changes of vestibular neuroanatomical properties predict a linear decay of VOR function. Nonetheless, human epidemiological data show a stable VOR function across the life span. In this study, we model cerebellum-dependent VOR adaptation to relate structural and functional changes throughout aging. We consider three neurosynaptic factors that may codetermine VOR adaptation during aging: the electrical coupling of inferior olive neurons, the long-term spike timing-dependent plasticity at parallel fiber – Purkinje cell synapses and mossy fiber – medial vestibular nuclei synapses, and the intrinsic plasticity of Purkinje cell synapses Our cross-sectional aging analyses suggest that long-term plasticity acts as a global homeostatic mechanism that underpins the stable temporal profile of VOR function. The results also suggest that the intrinsic plasticity of Purkinje cell synapses operates as a local homeostatic mechanism that further sustains the VOR at older ages. Importantly, the computational epidemiology approach presented in this study allows discrepancies among human cross-sectional studies to be understood in terms of interindividual variability in older individuals. Finally, our longitudinal aging simulations show that the amount of residual fibers coding for the peak and trough of the VOR cycle constitutes a predictive hallmark of VOR trajectories over a lifetime.

Lactate ions induce synaptic plasticity to enhance output from the central respiratory network.

Lactate ion sensing has emerged as a process that regulates ventilation during metabolic challenges. Most work has focused on peripheral sensing of lactate for the control of breathing. However, lactate also rises in the central nervous system (CNS) during disturbances to blood gas homeostasis and exercise. Using an amphibian model, we recently showed that lactate ions, independently of pH and pyruvate metabolism, act directly in the brainstem to increase respiratory-related motor outflow. This response had a long washout time and corresponded with potentiated excitatory synaptic strength of respiratory motoneurons. Thus, we tested the hypothesis that lactate ions enhance respiratory output using cellular mechanisms associated with long-term synaptic plasticity within motoneurons. In this study, we confirm that 2mM sodium lactate, but not sodium pyruvate, increases respiratory motor output in brainstem-spinal cord preparations, persisting for 2h upon the removal of lactate. Lactate also led to prolonged increases in the amplitude of AMPA-glutamate receptor (AMPAR) currents in individual motoneurons from brainstem slices. Both motor facilitation and AMPAR potentiation by lactate required classic effectors of synaptic plasticity, L-type Ca2+ channels and NMDA receptors, as part of the transduction process but did not correspond with increased expression of immediate-early genes often associated with activity-dependent neuronal plasticity. Altogether these results show that lactate ions enhance respiratory motor output by inducing conserved mechanisms of synaptic plasticity and suggest a new mechanism that may contribute to coupling ventilation to metabolic demands in vertebrates. KEY POINTS: Lactate ions, independently of pH and metabolism, induce long-term increases in respiratory-related motor outflow in American bullfrogs. Lactate triggers a persistent increase in strength of AMPA-glutamatergic synapses onto respiratory motor neurons. Long-term plasticity of motor output and synaptic strength by lactate involves L-type Ca2+ channels and NMDA-receptors as part of the transduction process. Enhanced AMPA receptor function in response to lactate in the intact network is causal for motor plasticity. In sum, well-conserved synaptic plasticity mechanisms couple the brainstem lactate ion concentration to respiratory motor drive in vertebrates.

The Alzheimer's disease risk gene CD2AP modulates mammalian synaptic structure and plasticity

CD2-Associated protein (CD2AP) is associated with increased risk of late-onset Alzheimer's disease. We have previously shown that loss of CD2AP's Drosophila homolog, cindr, exacerbates Tau toxicity and impairs synaptic maturation and function at the neuromuscular junction. However, little is understood about CD2AP at the central mammalian synapse. The present study demonstrates conservation of CD2AP function at the pre-synapse from fly to mouse, as well as characterizes CD2AP's role in maintaining post-synaptic structure and function.We examine short- and long-term plasticity using electrophysiologic measurements and synaptic structure and morphology using confocal imaging. Experiments were performed on homozygous CD2AP knockout mice and heterozygous CD2AP knockout mice to investigate potential haploinsufficient requirement. Mice constitutively expressing Cas9 endonuclease were used for brain-specific CD2AP knockout.Homozygous and heterozygous CD2AP knockout mice exhibit increased paired-pulse facilitation, a form of short-term plasticity. This matches data from Drosophila, implying conservation from fly to mouse, and indicates decreased probability of presynaptic vesicle release with CD2AP loss. We found no change in long-term potentiation (LTP) at 4 to 6 weeks; however, our preliminary experiments demonstrate decreased LTP in aged heterozygous CD2AP knockouts. Ongoing experiments are investigating age as a factor in CD2AP function. Lastly, CD2AP knockout neurons exhibit increased dendritic branching and homozygous knockout mice have increased expression of postsynaptic density protein 95.Our analyses implicate CD2AP in modulation of synaptic plasticity and structure, suggest a conservation of CD2AP function from flies to mice, and support CD2AP haploinsufficiency. Going forward, we will investigate how CD2AP loss affects existing Alzheimer's pathogenesis in a P301S tauopathy mouse model.

Synaptic tau and synaptogyrin‐3 are promising targets to tackle tauopathies

Different pathogenic conditions (Alzheimer's disease and other tauopathies) induce detachment of Tau protein from microtubules. Detached Tau accumulates at synapses and binds to synaptic vesicle-associated protein Synaptogyrin-3, hampering vesicle mobility and neurotransmitter release (Zhou et al., Nature Communications 2017). Lowering the levels of Synaptogyrin-3 alleviates synaptic dysfunction in fruit flies and mouse primary neurons McInnes et al., Neuron 2018).We pursued two strategies to lower Synaptogyrin-3 expression in a tauopathy mouse model (human P301S Tau-expressing mice; "PS19 mouse line"). We generated a synaptogyrin-3 knockout mouse usign CRISPR/Cas9 and crossed it with Tau P301S mice. In paralel, we designed several antisense oligonucleotides (ASOs) against common sequences of mouse and human Synaptogyrin-3.We showed that lowering expression of Synaptogyrin-3 is benign in mice, but strongly rescues mutant Tau-induced defects in long-term synaptic plasticity and working memory. We screened several anti-Synaptogyrin-3 ASOs in vitro and selected the most effective one to further study its effects in vivo.Lowering Synaptogyrin-3 is safe and sufficient to prevent cognitive decline in Tau P301S mice. Further research will determine the therapeutic potential of interfering with the interaction of Tau and Synaptogyrin-3 in the context of tauopathies.

Neonatal NMDA blockade alters the LTP, LTD and cognitive functions in male and female Wistar rats

There is compelling evidence that neonatal blockade of NMDA receptors by phencyclidine (PCP) is associated with cognitive impairment in adulthood but little is known about the effects of early life PCP treatment on synaptic function later in life. Here, we sought to determine whether early life exposure to PCP alters the electrophysiologic function of hippocampal CA1 neurons in adult rats. To this end, male and female Wistar rats received either saline or PCP (10 mg/kg) on postnatal days (PND) 7, 9, and 11, and then underwent separate behavioral and electrophysiology tests in adulthood. Neonatal PCP treatment did not alter basic synaptic transmission and had only a modest effect on frequency following (FF) capacity but significantly decreased the paired-pulse facilitation (PPF) in the Schaffer collateral (SC)–CA1 pathway. We found that PCP treatment significantly attenuated the long-term potentiation (LTP) and long-term depression (LTD) in CA1 neurons accompanied by pronounced alteration in complex response profile in adult rats. The electrophysiology data were comparable in male and female rats and reliably associated with impaired spatial reference and working memories in these animals. Overall, this study suggests that blockade of NMDA receptors during early life deteriorates the short-term and long-term synaptic plasticity and complex response profile of CA1 neurons in adulthood.

ZnO nanowire optoelectronic synapse for neuromorphic computing

Artificial synapses that integrate functions of sensing, memory and computing are highly desired for developing brain-inspired neuromorphic hardware. In this work, an optoelectronic synapse based on the ZnO nanowire (NW) transistor is achieved, which can be used to emulate both the short-term and long-term synaptic plasticity. Synaptic potentiation is present when the device is stimulated by light pulses, arising from the light-induced O2 desorption and the persistent photoconductivity behavior of the ZnO NW. On the other hand, synaptic depression occurs when the device is stimulated by electrical pulses in dark, which is realized by introducing a charge trapping layer in the gate dielectric to trap carriers. Simulation of a neural network utilizing the ZnO NW synapses is carried out, demonstrating a high recognition accuracy over 90% after only 20 training epochs for recognizing the Modified National Institute of Standards and Technology digits. The present nanoscale optoelectronic synapse has great potential in the development of neuromorphic visual systems.

ReSe2-Based RRAM and Circuit-Level Model for Neuromorphic Computing

Resistive random-access memory (RRAM) devices have drawn increasing interest for the simplicity of its structure, low power consumption and applicability to neuromorphic computing. By combining analog computing and data storage at the device level, neuromorphic computing system has the potential to meet the demand of computing power in applications such as artificial intelligence (AI), machine learning (ML) and Internet of Things (IoT). Monolayer rhenium diselenide (ReSe2), as a two-dimensional (2D) material, has been reported to exhibit non-volatile resistive switching (NVRS) behavior in RRAM devices with sub-nanometer active layer thickness. In this paper, we demonstrate stable multiple-step RESET in ReSe2 RRAM devices by applying different levels of DC electrical bias. Pulse measurement has been conducted to study the neuromorphic characteristics. Under different height of stimuli, the ReSe2 RRAM devices have been found to switch to different resistance states, which shows the potentiation of synaptic applications. Long-term potentiation (LTP) and depression (LTD) have been demonstrated with the gradual resistance switching behaviors observed in long-term plasticity programming. A Verilog-A model is proposed based on the multiple-step resistive switching behavior. By implementing the LTP/LTD parameters, an artificial neural network (ANN) is constructed for the demonstration of handwriting classification using Modified National Institute of Standards and Technology (MNIST) dataset.

Transcranial ultrasound stimulation of the human motor cortex

SummaryIt has been 40 years since the report of long-term synaptic plasticity on the rodent brain. Transcranial ultrasound stimulation (TUS) shows advantages in spatial resolution and penetration depth when compared with electrical or magnetic stimulation. The repetitive TUS (rTUS) can induce cortical excitability alteration on animals, and persistent aftereffects were observed. However, the effects of rTUS on synaptic plasticity in humans remain unelucidated. In the current study, we applied a 15-min rTUS protocol to stimulate left primary motor cortex (l-M1) in 24 male healthy participants. The single-pulsed transcranial magnetic stimulation-evoked motor evoked potential and Stop-signal task was applied to measure the rTUS aftereffects. Here, we report that conditioning the human motor cortex using rTUS may produce long-lasting and statistically significant effects on motor cortex excitability as well as motor behavior, without harmful side effects observed. These findings suggest a considerable potential of rTUS in cortical plasticity modulation and clinical intervention for impulsivity-related disorders.

Alterations in amperometric cholinergic signals accompanied by synaptic plasticity and γ oscillations in the hippocampus-medial prefrontal cortex pathway.

Neural projections from the ventral hippocampal CA1 (vCA1) to the medial prefrontal cortex (mPFC) and from the posterior dorsal hippocampal CA1 (pdCA1) to the mPFC are important for information processing. Previous studies have revealed that two forms of long-term synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), and γ oscillations, which are all believed to be neural bases for learning and memory in the vCA1-mPFC and the pdCA1-mPFC pathways, exhibited distinct profiles. However, the underlying mechanism is unclear. In the present study, amperometric cholinergic signals were monitored during in-vivo electrophysiological recordings of evoked extracellular postsynaptic potentials and spontaneous local field potentials. The results demonstrated that in the vCA1-mPFC pathway, increased cholinergic currents and γ power of the amperometric cholinergic signals were accompanied by the induction of LTD and increased γ power of local field potentials, whereas, in the pdCA1-mPFC pathway, decreased cholinergic currents and increased γ power of the amperometric cholinergic signals were accompanied by the induction of LTP and increased γ power of local field potentials. These findings indicated that some correlations may exist between amperometric cholinergic signals and synaptic plasticity in the hippocampus-mPFC pathway. The pattern of alterations in cholinergic signals may help to illustrate the specific properties of synaptic plasticity and γ oscillations in the vCA1-mPFC and the pdCA1-mPFC pathways.

Emphasizing roles of BDNF promoters and inducers in Alzheimer's disease for improving impaired cognition and memory.

Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophic factor adding to neurons' development and endurance. The amount of BDNF present in the brain determines susceptibility to various neurodegenerative diseases. In Alzheimer's disease (AD), often it is seen that low levels of BDNF are present, which primarily contributes to cognition deficit by regulating long-term potentiation (LTP) and synaptic plasticity. Molecular mechanisms underlying the synthesis, storage and release of BDNF are widely studied. New molecules are found, which contribute to the signal transduction pathway. Two important receptors of BDNF are TrkB and p75NTR. When BDNF binds to the TrkB receptor, it activates three main signalling pathways-phospholipase C, MAPK/ERK, PI3/AKT. BDNF holds an imperative part in LTP and dendritic development, which are essential for memory formation. BDNF supports synaptic integrity by influencing LTP and LTD. This action is conducted by modulating the glutamate receptors; AMPA and NMDA. This review paper discusses the aforesaid points along with inducers of BDNF. Drugs and herbals promote neuroprotection by increasing the hippocampus' BDNF level in various disease-induced animal models for neurodegeneration. Advancement in finding pertinent molecules contributing to the BDNF signalling pathway has been discussed, along with the areas that require further research and study.

A ZnO micro/nanowire-based photonic synapse with piezo-phototronic modulation

Neuromorphic computing systems that emulate the working principle of the biological brain is capable of overcoming the von Neumann bottleneck. Artificial synapses are critical information processing units in the neuromorphic computing systems. Because of the fast speed, large bandwidth, and high reliability, light or photonic interaction controlled artificial synapses (i.e., photonic synapses) are receiving great attention in recent years. Applying an additional stimuli to the photonic synapse will lead to a multi-level adjustment of synaptic plasticity behavior, which is useful for developing a multi-sensory neuromorphic system. In this work, we present a transparent and flexible photonic synapse based on a single ZnO micro/nanowire with modulation by piezo-phototronic effect, which is coupling by strain-induced piezoelectric effect and photoexcitation. The synaptic functions including paired-pulse facilitation, short-term plasticity, and long-term plasticity are demonstrated with pulsed UV illumination. Furthermore, the synaptic weight change can be effectively modulated by applying compressive strains due to the piezo-phototronic effect induced in the ZnO micro/nanowire. Specifically, the weight change can be reduced from 1437.5% to 191.4% with a compressive strain change from −0.00% to −0.28% under a UV light pulse of 4.2 mW cm−2. A mechanism is proposed to explain the observed phenomenon of the photonic synapse under compressive strains. In addition, the relaxation of long-term plasticity can be modulated by controlling the transport of photo-generated carriers through the Schottky contact via the piezo-phototronic effect. This work demonstrates an effective approach to developing photonic synapses with tunable functions for multi-sensory neuromorphic computing systems.

Analog Synaptic Transistor with Al-Doped HfO2 Ferroelectric Thin Film.

Neuromorphic computing has garnered significant attention because it can overcome the limitations of the current von-Neumann computing system. Analog synaptic devices are essential for realizing hardware-based artificial neuromorphic devices; however, only a few systematic studies in terms of both synaptic materials and device structures have been conducted so far, and thus, further research is required in this direction. In this study, we demonstrate the synaptic characteristics of a ferroelectric material-based thin-film transistor (FeTFT) that uses partial switching of ferroelectric polarization to implement analog conductance modulation. For a ferroelectric material, an aluminum-doped hafnium oxide (Al-doped HfO2) thin film was prepared by atomic layer deposition. As an analog synaptic device, our FeTFT successfully emulated short-term plasticity and long-term plasticity characteristics, such as paired-pulse facilitation and spike timing-dependent plasticity. In addition, we obtained potentiation/depression weight updates with high linearity, an on/off ratio, and low cycle-to-cycle variation by adjusting the amplitude and number of input pulses. In the simulation trained with optimized potentiation/depression conditions, we achieved a pattern recognition accuracy of approximately 90% for the Modified National Institute of Standard and Technology (MNIST) handwritten data set. Our results indicated that ferroelectric transistors can be used as an alternative artificial synapse.

Dendritic Organic Electrochemical Transistors Grown by Electropolymerization for 3D Neuromorphic Engineering.

One of the major limitations of standard top‐down technologies used in today's neuromorphic engineering is their inability to map the 3D nature of biological brains. Here, it is shown how bipolar electropolymerization can be used to engineer 3D networks of PEDOT:PSS dendritic fibers. By controlling the growth conditions of the electropolymerized material, it is investigated how dendritic fibers can reproduce structural plasticity by creating structures of controllable shape. Gradual topologies evolution is demonstrated in a multielectrode configuration. A detailed electrical characterization of the PEDOT:PSS dendrites is conducted through DC and impedance spectroscopy measurements and it is shown how organic electrochemical transistors (OECT) can be realized with these structures. These measurements reveal that quasi‐static and transient response of OECTs can be adjusted by controlling dendrites’ morphologies. The unique properties of organic dendrites are used to demonstrate short‐term, long‐term, and structural plasticity, which are essential features required for future neuromorphic hardware development.

Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum.

Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs, although their exact function has remained controversial. Here, we identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons. Interfering with astrocyte NMDAR or GluN2C NMDAR activity reduces the range of presynaptic strength distribution specifically in the stratum radiatum inputs without an appreciable change in the mean presynaptic strength. Mathematical modeling shows that narrowing of the width of presynaptic release probability distribution compromises the expression of long-term synaptic plasticity. Our findings suggest a novel feedback signaling system that uses astrocyte GluN2C NMDARs to adjust basal synaptic weight distribution of Schaffer collateral inputs, which in turn impacts computations performed by the CA1 pyramidal neuron.