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| Open AccessInhibitory neurotransmission drives endocannabinoid degradation to promote memory consolidation
Endocannabinoid levels are controlled by the fine balance between their synthesis and degradation. Here, the authors show that memory formation through fear conditioning selectively accelerates the degradation of endocannabinoids in the cerebellum via a lasting increase in GABA release.
- Christophe J. Dubois
- , Jessica Fawcett-Patel
- & Siqiong June Liu
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Article
| Open AccessTactile modulation of memory and anxiety requires dentate granule cells along the dorsoventral axis
Touch can positively modulate cognitive performance and emotional response. Here the authors demonstrate that enriched tactile experience improves memory and reduces anxiety in adult mice by remodelling the pathway from the primary somatosensory cortex to the dentate gyrus.
- Chi Wang
- , Hui Liu
- & Xiao-Dong Wang
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Article
| Open AccessAcute EPA-induced learning and memory impairment in mice is prevented by DHA
Acute administration of EPA impairs learning and memory and hippocampal LTP in mice that was mediated through enhancing GABAergic transmission via the 5-HT6R. DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT2CR.
- Ji-Hong Liu
- , Qian Wang
- & Tian-Ming Gao
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Article
| Open AccessSynaptic vesicle traffic is supported by transient actin filaments and regulated by PKA and NO
Transport of membrane proteins within the cell is thought to mainly rely on microtubule-based transport, but the role of microtubules in neuronal cell recycling of synaptic vesicles is unclear. Here, the authors show that axonal movement of recycling vesicles may be driven not by microtubules but primarily by actin polymerization.
- Nicolas Chenouard
- , Feng Xuan
- & Richard W. Tsien
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Article
| Open AccessEndoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses
In hippocampal pyramidal cells, a subset of dendritic spines contain endoplasmic reticulum (ER). Here, the authors show that ER enters dendritic spines in a non-random manner, during high synaptic activity with the function of limiting synaptic strength.
- Alberto Perez-Alvarez
- , Shuting Yin
- & Thomas G. Oertner
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Article
| Open AccessSurfaceome dynamics reveal proteostasis-independent reorganization of neuronal surface proteins during development and synaptic plasticity
Cell surface proteins contribute to neuronal development and activity-dependent synaptic plasticity. Here, the authors perform a time-resolved surfaceome analysis of developing primary neurons and in response to homeostatic synaptic scaling and chemical long-term potentiation (cLTP), revealing surface proteome remodeling largely independent of global proteostasis.
- Marc van Oostrum
- , Benjamin Campbell
- & Bernd Wollscheid
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Article
| Open AccessInterneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output
Inhibitory interneuron subtypes differentially control place cell representations in CA1. Here, the authors show that parvalbumin and somatostatin interneuron synapses onto CA1 pyramidal neurons exhibit distinct plasticity mechanisms and incorporating this insight into circuit-level modeling leads to stable place cell representations.
- Matt Udakis
- , Victor Pedrosa
- & Jack R. Mellor
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| Open AccessAstrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development
Presynaptic spike timing-dependent long-term depression at hippocampal CA3-CA1 synapses is evident until the third postnatal week in mice. The authors show that maturation beyond four weeks is associated with a switch to long-term potentiation in which astrocytes play a central role.
- Rafael Falcón-Moya
- , Mikel Pérez-Rodríguez
- & Antonio Rodríguez-Moreno
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Article
| Open AccessReduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
Stein, Barbosa et al. show that anti-NMDAR encephalitis and schizophrenia are characterized by reduced serial dependence in spatial working memory. Cortical network simulations show that this can be parsimoniously explained by a reduction in NMDAR-dependent short-term synaptic potentiation in these diseases.
- Heike Stein
- , Joao Barbosa
- & Albert Compte
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Article
| Open AccessDifferential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization
Inhibition in spinal nociceptive pathways is weaker and more labile in lamina I —where thermal input is primarily processed— than in lamina II that encodes predominantly high threshold mechanical input. This explains why noxious thermal input makes spinal circuits prone to catastrophic sensitization.
- Francesco Ferrini
- , Jimena Perez-Sanchez
- & Yves De Koninck
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Article
| Open AccessA solution to the learning dilemma for recurrent networks of spiking neurons
Bellec et al. present a mathematically founded approximation for gradient descent training of recurrent neural networks without backwards propagation in time. This enables biologically plausible training of spike-based neural network models with working memory and supports on-chip training of neuromorphic hardware.
- Guillaume Bellec
- , Franz Scherr
- & Wolfgang Maass
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Article
| Open AccessAutophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling
NMDA receptor-dependent long-term depression (NMDAR-LTD) is a form of synaptic plasticity mediated by reduced recycling of AMPA receptors to the plasma membrane. Here the authors show that autophagy is a regulator of this endocytic recycling and autophagy upregulation dampens NMDAR-LTD in adulthood.
- Hongmei Shen
- , Huiwen Zhu
- & Zheng Li
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Article
| Open AccessFMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome
Fragile X Mental Retardation Protein regulates synaptic plasticity and its loss results in Fragile X Syndrome. Here, the authors show that the FMRP(1-297)-tat peptide can permeate the BBB, restore protein translation and mossy fiber LTP, and reduce elevated levels of activity in Fmr1 KO mice.
- Xiaoqin Zhan
- , Hadhimulya Asmara
- & Ray W. Turner
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Article
| Open AccessStress gates an astrocytic energy reservoir to impair synaptic plasticity
Enduring changes in synaptic efficacy are highly sensitive to stress. Here, the authors show that astrocytic delivery of metabolites has an important role in the stress-mediated impairment of synaptic plasticity.
- Ciaran Murphy-Royal
- , April D. Johnston
- & Grant R. Gordon
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Article
| Open AccessImpact of functional synapse clusters on neuronal response selectivity
The formation of functional synaptic clusters (FSCs) and their impact on somatic membrane potential (sVm) in vivo are poorly understood. Here, the authors develop a computational approach to show that FSCs have to form via local rather than global plasticity and be moderately large to impact sVm.
- Balázs B. Ujfalussy
- & Judit K. Makara
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Article
| Open AccessEncoding of contextual fear memory in hippocampal–amygdala circuit
Previous studies implicate the hippocampal–amygdala pathway in contextual fear conditioning, in which animals learn to associate a neutral context with an aversive stimulus and display fear responses to dangerous situations. Here the authors show that selective strengthening of hippocampal–amygdala pathway contributes to encoding adaptive fear memory for threat-predictive context.
- Woong Bin Kim
- & Jun-Hyeong Cho
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Article
| Open AccessEarly life experiences selectively mature learning and memory abilities
The mechanisms underlying the maturation of learning and memory abilities are poorly understood. Here, authors show that episodic learning produces persistent neuronal activation, BDNF-dependent increase in excitatory synapse markers (synaptophysin and PSD-95), and significant maturation of AMPA receptor synaptic responses in the hippocampus of infant rats and mice compared to juveniles and adults.
- Benjamin Bessières
- , Alessio Travaglia
- & Cristina M. Alberini
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Article
| Open AccessAudio-visual experience strengthens multisensory assemblies in adult mouse visual cortex
Sensory stimuli usually arrive simultaneously but the neural-circuit mechanisms that combine multiple streams of sensory information are incompletely understood. The authors here show that visual-auditory pairing drives plasticity in multi-modal neuron networks within the mouse visual cortex.
- Thomas Knöpfel
- , Yann Sweeney
- & Samuel J. Barnes
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Article
| Open AccessSIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals
There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. In this study, authors demonstrate that axonal retrograde transport of BDNF/TrkB in neuronal amphisomes is involved in plasticity-relevant local signaling at presynaptic boutons and that SIPA1L2, a member of the SIPA1L family of neuronal RapGAPs, associates via LC3b to TrkB-containing amphisomes to regulate its motility and signaling at the axon terminals
- Maria Andres-Alonso
- , Mohamed Raafet Ammar
- & Michael R. Kreutz
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| Open AccessAMPA receptors in the synapse turnover by monomer diffusion
The mechanisms regulating the turnover of the AMPARs in the synapse, which is critically important to sustain basic synaptic activity, remains unclear. In this study, authors used single-molecule imaging techniques to demonstrate that AMPAR tetramers are not stable entities and readily fall apart to dimers and monomers that could reform to tetramers at the synapse, and that rapidly diffusing monomers in the plasma membrane are primarily responsible for the AMPAR turnover in the synapse.
- Jyoji Morise
- , Kenichi G. N. Suzuki
- & Shogo Oka
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Article
| Open AccessMaternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms
It’s well known that hippocampal synaptic plasticity and memory are impaired in experimental models of metabolic diseases, however, it is unclear if maternal diet or metabolic alterations around the gestational age may multigenerationally affect learning and memory. In this study, authors demonstrate that maternal high fat diet-dependent insulin resistance affects synaptic plasticity and memory of descendants until the third generation via reduced exon specific brain-derived neurotrophic factor expression in the hippocampus of descendants
- Salvatore Fusco
- , Matteo Spinelli
- & Claudio Grassi
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Article
| Open AccessStable memory with unstable synapses
How are stable memories maintained in the brain despite significant ongoing fluctuations in synaptic strengths? Here, the authors show that a model consistent with fluctuations, homeostasis and biologically plausible learning rules, naturally leads to memories implemented as dynamic attractors.
- Lee Susman
- , Naama Brenner
- & Omri Barak
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Article
| Open AccessMultiplexed and high-throughput neuronal fluorescence imaging with diffusible probes
Multiplexed imaging of synaptic proteins can provide useful information on the heterogeneity of synaptic architecture and plasticity. Here the authors use high affinity locked nucleic acid probes and low affinity DNA imaging probes to achieve multiplexed confocal and super-resolution imaging of synaptic and cytoskeletal proteins.
- Syuan-Ming Guo
- , Remi Veneziano
- & Mark Bathe
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Article
| Open AccessCaspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling
Caspase-2 is constitutively expressed in neurons yet its physiological function is not known. Here, the authors report a role for Caspase-2 activity in synaptic plasticity via a reduction in dendritic spine density through cleavage of Rictor suggesting a mechanism to explain the impairments in cognitive flexibility observed in Caspase-2 knockout mice.
- Zhi-Xiang Xu
- , Ji-Wei Tan
- & Baoji Xu
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Article
| Open AccessLive cell imaging reveals 3′-UTR dependent mRNA sorting to synapses
Asymmetric subcellular mRNA distribution is important for local translation of neuronal mRNAs. Here the authors employed MS2 live-cell imaging and showed that the reporter mRNA containing the 3’ UTR of Rgs4 shows an anterograde transport bias, dependent on neuronal activity and the protein Staufen2, and mediates sustained mRNA recruitment to synapses.
- Karl E. Bauer
- , Inmaculada Segura
- & Michael A. Kiebler
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Article
| Open AccessCul3 and insomniac are required for rapid ubiquitination of postsynaptic targets and retrograde homeostatic signaling
The authors use a forward genetic screen to discover postsynaptic factors required for homeostatic synaptic plasticity at the Drosophila neuromuscular junction. They identify insomniac and the ubiquitin ligase Cul3, genes involved in sleep regulation, to be necessary for retrograde homeostatic signalling at this synapse.
- Koto Kikuma
- , Xiling Li
- & Dion Dickman
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Article
| Open AccessAstrocytic p38α MAPK drives NMDA receptor-dependent long-term depression and modulates long-term memory
How astrocytes influence neuronal plasticity remains unclear, as they are typically considered as modulators of core mechanisms driven by neuronal components. Here, authors show that Long-term depression (LTD) induction in the hippocampus triggers calcium signaling in the astrocyte and enhances SNARE-dependent astrocytic glutamate release, which is then responsible for the activation of postsynaptic NMDA receptors and synaptic depression.
- Marta Navarrete
- , María I. Cuartero
- & José A. Esteban
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Article
| Open AccessMechanisms of Ca2+/calmodulin-dependent kinase II activation in single dendritic spines
Activation of Ca2+/calmodulin-dependent kinase II (CaMKII) in dendritic spines is a key step of long-term potentiation (LTP) induction, yet the exact biochemical steps of CaMKIIα activation in dendritic spines remained elusive. In this study, the authors developed a novel imaging approach to monitor CaM interactions CaMKIIα in cultured hippocampal neurons after uncaging of glutamate. This allowed the authors to model the kinetics of CaMKIIα activation in single dendritic spines.
- Jui-Yun Chang
- , Yoshihisa Nakahata
- & Ryohei Yasuda
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Article
| Open AccessExcitatory rubral cells encode the acquisition of novel complex motor tasks
The red nucleus (RN) is a midbrain nucleus known to be involved in the fine control of limb movements, but its role in motor learning is unclear. Here, the authors identified a neuronal population within the red nucleus, co-expressing Vglut2, PV and C1Ql2, which undergoes training-dependent plasticity.
- Giorgio Rizzi
- , Mustafa Coban
- & Kelly R. Tan
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Article
| Open AccessSIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice
Intermittent fasting has been shown to have beneficial effects on hippocampal function in rodents, but the underlying mechanism is not fully understood. Here the authors show that the mitochondrial protein SIRT3 contributes to the beneficial cognitive and synaptic effects of intermittent fasting in mice.
- Yong Liu
- , Aiwu Cheng
- & Mark P. Mattson
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Article
| Open AccessLower synaptic density is associated with depression severity and network alterations
Lowered synaptic density is believed to occur in major depressive disorder and PTSD, possibly as an effect of stress. Here, the authors use positron emission tomography (PET) to measure levels of the synaptic marker SV2A and show that SV2A density is lower in those with more severe symptoms of depression.
- Sophie E. Holmes
- , Dustin Scheinost
- & Irina Esterlis
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| Open AccessMultiplex imaging relates quantal glutamate release to presynaptic Ca2+ homeostasis at multiple synapses in situ
How neurotransmitter release relates to presynaptic calcium dynamics is not fully understood. Here the authors develop an approach based on FLIM and optical quantal analysis for simultaneous imaging of calcium dynamics and glutamate release at presynaptic boutons.
- Thomas P. Jensen
- , Kaiyu Zheng
- & Dmitri A. Rusakov
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Article
| Open AccessNeuroinspired unsupervised learning and pruning with subquantum CBRAM arrays
To realize the potential of resistive RAM crossbar arrays as platforms for neuromorphic computing, reduced network-level energy consumption must be achieved. Here, the authors use a hardware/software co-design approach to realize reduced energy consumption during network training for the network.
- Yuhan Shi
- , Leon Nguyen
- & Duygu Kuzum
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Article
| Open AccessPresenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity
Mutations in presenilin, which cleaves amyloid precursor protein, cause familial Alzheimer’s Disease. Here, the authors show that loss of presenilin leads to loss of synaptotagmin 7, leading to impaired presynaptic release.
- Gaël Barthet
- , Tomàs Jordà-Siquier
- & Christophe Mulle
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Article
| Open AccessModulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington’s disease models
Cognitive decline in Huntington’s disease (HD) may be due to impaired hippocampal synaptic plasticity. In this study the authors show that AMPA receptor surface diffusion, a key player in synaptic plasticity, is deregulated in multiple HD mouse models as a result of impaired BDNF signalling that underlies the memory deficits, and can be pharmacologically rescued.
- Hongyu Zhang
- , Chunlei Zhang
- & Daniel Choquet
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Article
| Open AccessDopamine–endocannabinoid interactions mediate spike-timing-dependent potentiation in the striatum
Dopamine tightly regulates plasticity at corticostriatal synapses. Here, the authors report that endocannabinoid dependent LTP induced with few spikes in the striatum is impaired in a rodent model of Parkinson’s disease, requires dopamine through presynaptic D2 receptors located on corticostriatal inputs.
- Hao Xu
- , Sylvie Perez
- & Laurent Venance
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Article
| Open AccessOverexpression of endophilin A1 exacerbates synaptic alterations in a mouse model of Alzheimer’s disease
Endophilin A1 protein is known to be elevated in Alzheimer’s disease (AD). Here the authors show that endophilin A1 overexpression exacerbates synaptic deficits in a mouse model of AD.
- Qing Yu
- , Yongfu Wang
- & Shirley ShiDu Yan
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Article
| Open AccessExcitatory synaptic dysfunction cell-autonomously decreases inhibitory inputs and disrupts structural and functional plasticity
Both inhibitory and excitatory input development are shaped by activity, but one may be dependent on the other. Here, the authors examine plasticity of inhibitory inputs in vivo, as well as behavioral consequences in tadpoles where excitatory transmission has been impaired.
- Hai-yan He
- , Wanhua Shen
- & Hollis T. Cline
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Article
| Open AccessNicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum
Despite its known effects in brain reward centers, nicotine can be aversive in high doses. Here, the authors show that nicotine aversion depends on low-affinity nicotinic acetylcholine receptors expressed on projections from the interpeduncular nucleus to the laterodorsal tegmentum.
- Shannon L. Wolfman
- , Daniel F. Gill
- & Daniel S. McGehee
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Article
| Open AccessON-OFF receptive fields in auditory cortex diverge during development and contribute to directional sweep selectivity
Auditory cortex neurons exhibit distinct frequency tuning to sound onset and offset. Here the authors demonstrate that during development ON-OFF receptive fields diverge to occupy adjacent frequency ranges that may underlie their direction selective responses to frequency modulated sweeps.
- Joseph Sollini
- , Gaëlle A. Chapuis
- & Paul Chadderton
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Article
| Open AccessAlcohol exposure disrupts mu opioid receptor-mediated long-term depression at insular cortex inputs to dorsolateral striatum
µ-opioid receptors (MOR) are known to modulate the reward effects of drugs of abuse, and MOR activation induces long-term depression (LTD) at striatal synapses. Here the authors show that alcohol exposure disrupts MOR-induced LTD only at specific cortical inputs to the striatum.
- Braulio Muñoz
- , Brandon M. Fritz
- & Brady K. Atwood
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Article
| Open AccessDysbindin links presynaptic proteasome function to homeostatic recruitment of low release probability vesicles
At the fly neuromuscular junction, postsynaptic receptor perturbation induces homeostatic enhancement of neurotransmitter release. Here, the authors show that the presynaptic proteasome controls a vesicle pool required for homeostatic plasticity and that dysbindin is required to access this pool.
- Corinna Wentzel
- , Igor Delvendahl
- & Martin Müller
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Article
| Open AccessCKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus
The function of receptor desensitization in vivo is not well understood. Here, the authors show that deletion of CKAMP44, an AMPAR auxiliary protein that modulates desensitization of AMPAR currents, affects synaptic facilitation at retinogeniculate synapses and visually-evoked firing in awake mice.
- Xufeng Chen
- , Muhammad Aslam
- & Jakob von Engelhardt
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Article
| Open AccessInput-dependent regulation of excitability controls dendritic maturation in somatosensory thalamocortical neurons
Sensory input and neuronal activity are crucial for proper morphological development of neurons. Here, Frangeul and colleagues show that membrane excitability is a critical component of dendritic development in mouse somatosensory thalamocortical neurons.
- Laura Frangeul
- , Vassilis Kehayas
- & Denis Jabaudon
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Article
| Open AccessBrain insulin resistance impairs hippocampal synaptic plasticity and memory by increasing GluA1 palmitoylation through FoxO3a
Metabolic diseases have been associated with cognitive impairment. Here, the authors show that brain insulin resistance induced by high-fat diet leads to increased palmitoylation of AMPA receptors and thus changes in hippocampal plasticity, learning and memory.
- Matteo Spinelli
- , Salvatore Fusco
- & Claudio Grassi
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Article
| Open AccessAltered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice
Dysfunction of mGluR5 has been implicated in Fragile X syndrome. Here, using a single-molecule tracking technique, the authors found an increased lateral mobility of mGluR5 at the synaptic site in Fmr1 KO hippocampal neurons, leading to abnormal NMDAR-mediated synaptic plasticity and cognitive deficits.
- Elisabetta Aloisi
- , Katy Le Corf
- & Andreas Frick
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Article
| Open AccessFlexible three-dimensional artificial synapse networks with correlated learning and trainable memory capability
High-density information storage calls for the development of modern electronics with multiple stacking architectures that increase the complexity of three-dimensional interconnectivity. Here, Wu et al. build a stacked yet flexible artificial synapse network using layer-by-layer solution processing.
- Chaoxing Wu
- , Tae Whan Kim
- & J. Joshua Yang
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Article
| Open AccessModeling somatic and dendritic spike mediated plasticity at the single neuron and network level
Synaptic plasticity is the neuronal mechanism underlying learning. Here the authors construct biophysical models of pyramidal neurons that reproduce observed plasticity gradients along the dendrite and show that dendritic spike dependent LTP which is predominant in distal sections can prolong memory retention.
- Jacopo Bono
- & Claudia Clopath
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Article
| Open AccessCortical Up states induce the selective weakening of subthreshold synaptic inputs
Slow oscillations between cortical Up and Down states are a defining feature of deep sleep, but their function is not well understood. Here the authors study Up/Down states in acute slices of entorhinal cortex, and find that Up states promote the weakening of subthreshold synaptic inputs, while suprathreshold inputs are preserved or strengthened.
- Julian Bartram
- , Martin C. Kahn
- & Edward O. Mann