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| Open AccessGlioma synapses recruit mechanisms of adaptive plasticity
In glioma, malignant synapses hijack mechanisms of synaptic plasticity to increase glutamate-dependent currents in tumour cells and the formation of neuron–glioma synapses, thereby promoting tumour proliferation and progression.
- Kathryn R. Taylor
- , Tara Barron
- & Michelle Monje
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Article
| Open AccessLTP induction by structural rather than enzymatic functions of CaMKII
Several independent lines of evidence demonstrated long-term potentiation induction by a structural function of calmodulin-dependent protein kinase II rather than by its enzymatic activity.
- Jonathan E. Tullis
- , Matthew E. Larsen
- & K. Ulrich Bayer
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Article |
Filopodia are a structural substrate for silent synapses in adult neocortex
A study using super-resolution protein imaging to visualize synaptic proteins from layer 5 pyramidal neurons in the primary visual cortex of adult mice shows that filopodia are a structural substrate for silent synapses.
- Dimitra Vardalaki
- , Kwanghun Chung
- & Mark T. Harnett
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Article
| Open AccessEntorhinal cortex directs learning-related changes in CA1 representations
Analysis of the activity of CA1 cells in mice performing a learning task shows that the entorhinal cortex signals behavioural timescale synaptic plasticity to generate learning-related changes in the hippocampus.
- Christine Grienberger
- & Jeffrey C. Magee
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Article |
Fast resupply of synaptic vesicles requires synaptotagmin-3
Synaptotagmin-3 is identified as the presynaptic high-affinity calcium sensor to rapidly replenish synaptic vesicles to maintain steady synaptic transmission.
- Dennis J. Weingarten
- , Amita Shrestha
- & Skyler L. Jackman
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Article |
Local circuit amplification of spatial selectivity in the hippocampus
Single-cell tracing and optogenetics manipulation in mice are used to show how spatial tuning of individual pyramidal cells in CA1 can propagate to and be amplified by their local subnetwork of neurons.
- Tristan Geiller
- , Sadra Sadeh
- & Attila Losonczy
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Article |
Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis
A mechanism of mechanosensation and transduction in the presynaptic boutons is identified, in which sensing of fine pressure leads to enhanced neurotransmitter release.
- Hasan Ucar
- , Satoshi Watanabe
- & Haruo Kasai
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Article |
Cortical response selectivity derives from strength in numbers of synapses
Live neuron imaging and electron microscopy reconstruction shows that the selectivity of cortical neuron responses to visual stimuli arises from the total number of synapses activated rather than being dominated by a small number of strong synaptic inputs.
- Benjamin Scholl
- , Connon I. Thomas
- & David Fitzpatrick
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Article |
Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network
Novel experiences in mice lead to opposing effects on inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin- and cholecystokinin-expressing interneurons, revealing the roles of FOS and SCG2 in neural plasticity and consolidation of memories.
- Ee-Lynn Yap
- , Noah L. Pettit
- & Michael E. Greenberg
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Article |
eIF2α controls memory consolidation via excitatory and somatostatin neurons
Stimulation of de novo protein synthesis in both excitatory and inhibitory, somatostatin-expressing neurons in the mouse hippocampus enhances memory consolidation.
- Vijendra Sharma
- , Rapita Sood
- & Nahum Sonenberg
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Letter |
Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses
Dopamine-independent induction of long-term potentiation at hippocampal synapses onto the nucleus accumbens modulates reward-related behaviour.
- Tara A. LeGates
- , Mark D. Kvarta
- & Scott M. Thompson
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Letter |
Synaptotagmin 7 confers frequency invariance onto specialized depressing synapses
The calcium-sensing protein synaptotagmin 7 mediates facilitation that is masked by depression, but supports frequency-invariant transmission in mouse cerebellar and vestibular synapses.
- Josef Turecek
- , Skyler L. Jackman
- & Wade G. Regehr
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Letter |
Retrograde semaphorin–plexin signalling drives homeostatic synaptic plasticity
At the neuromuscular junction in Drosophila, signalling from postsynaptic Sema2b to presynaptic PlexB controls presynaptic homeostatic plasticity through Mical-mediated regulation of the readily releasable pool of synaptic vesicles.
- Brian O. Orr
- , Richard D. Fetter
- & Graeme W. Davis
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Letter |
Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors
Surface diffusion of AMPA receptors, from extra-synaptic to synaptic sites at the plasma membrane, is essential for full long-term potentiation in hippocampal neurons and for fear conditioning in living mice.
- A. C. Penn
- , C. L. Zhang
- & D. Choquet
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Article |
Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP
Postsynaptic synaptotagmin-1 and synaptotagmin-7 mediate calcium-dependent exocytosis of AMPA receptors during long-term potentiation.
- Dick Wu
- , Taulant Bacaj
- & Thomas C. Südhof
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Letter |
Autocrine BDNF–TrkB signalling within a single dendritic spine
Live fluorescent imaging of murine hippocampal slices shows that NMDAR-dependent glutamate signalling leads to postsynaptic BDNF release, with associated signalling of its receptor, TrkB, on the same dendritic spine, suggesting autocrine BDNF signalling.
- Stephen C. Harward
- , Nathan G. Hedrick
- & James O. McNamara
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Letter |
Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity
The three small GTPases Rac1, RhoA and Cdc42 are differentially involved in structural long-term potentiation of rodent dendritic spines, simultaneously ensuring signal specificity and also priming the system for plasticity.
- Nathan G. Hedrick
- , Stephen C. Harward
- & Ryohei Yasuda
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Letter |
Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons
Igf1 is identified in mice as an experience-induced gene that functions cell-autonomously to increase inhibitory input onto a disinhibitory subtype of GABAergic neurons in the cortex, affecting the downstream excitation–inhibition balance within circuits that regulate visual acuity, and providing a novel example of experience modulating neural plasticity.
- A. R. Mardinly
- , I. Spiegel
- & M. E. Greenberg
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Letter |
The calcium sensor synaptotagmin 7 is required for synaptic facilitation
Synaptotagmin 7 is shown to be essential for synaptic facilitation at a variety of central synapses, and the results pave the way for future functional studies of short-term synaptic plasticity, a fundamental form of neuronal computation.
- Skyler L. Jackman
- , Josef Turecek
- & Wade G. Regehr
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Article |
Labelling and optical erasure of synaptic memory traces in the motor cortex
A new light-activated probe that targets recently active neuronal spines for manipulation induces shrinkage of recently potentiated spines following a motor learning task; spine shrinkage disrupted learning, suggesting a causal relationship between the specific subset of targeted spines and the learned behaviour.
- Akiko Hayashi-Takagi
- , Sho Yagishita
- & Haruo Kasai
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Letter |
A circuit mechanism for differentiating positive and negative associations
Neurons in the basolateral amygdala projecting to canonical fear or reward circuits undergo opposing changes in synaptic strength following fear or reward conditioning, and selectively activating these projection-target-defined neural populations causes either negative or positive reinforcement, respectively.
- Praneeth Namburi
- , Anna Beyeler
- & Kay M. Tye
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Article |
Oxytocin enables maternal behaviour by balancing cortical inhibition
A study of pup retrieval behaviour in mice shows that oxytocin modulates cortical responses to pup calls specifically in the left auditory cortex; in virgin females, call-evoked responses were enhanced, thus increasing their salience, by pairing oxytocin delivery in the left auditory cortex with the calls, suggesting enhancement was a result of balancing the magnitude and timing of inhibition with excitation.
- Bianca J. Marlin
- , Mariela Mitre
- & Robert C. Froemke
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Article |
Branch-specific dendritic Ca2+ spikes cause persistent synaptic plasticity
Ca2+ spikes are generated on different dendritic branches in the primary motor cortex of mice performing different motor learning tasks, causing long-lasting potentiation of postsynaptic dendritic spines; inactivation of a population of interneurons disrupts the spatial separation of Ca2+ spikes and persistent dendritic spine potentiation, suggesting that the generation of Ca2+ spikes on different dendritic branches is crucial for storing information in individual neurons.
- Joseph Cichon
- & Wen-Biao Gan
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Letter |
Calcium transient prevalence across the dendritic arbour predicts place field properties
In vivo evidence for the existence of regenerative dendritic events in place cell dendrites of awake, behaving mice suggests an active role for dendritic spikes in building the representation of space in the hippocampus.
- Mark E. J. Sheffield
- & Daniel A. Dombeck
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Letter |
Sensory-evoked LTP driven by dendritic plateau potentials in vivo
Whole-cell recordings in mouse somatosensory cortex in vivo show that rhythmic sensory-whisker stimulation induces long-term synaptic potentiation (LTP) in layer 2/3 (L2/3) pyramidal cells, in the absence of somatic spikes, through long-lasting NMDAR-mediated depolarizations that are generated by synaptic networks originating from the posteromedial complex of the thalamus.
- Frédéric Gambino
- , Stéphane Pagès
- & Anthony Holtmaat
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Article |
NMDA receptor structures reveal subunit arrangement and pore architecture
X-ray crystal structures are presented of the N-methyl-d-aspartate (NMDA) receptor, a calcium-permeable ion channel that opens upon binding of glutamate and glycine; glutamate is a key excitatory neurotransmitter and enhanced structural insight of this receptor may aid development of therapeutic small molecules.
- Chia-Hsueh Lee
- , Wei Lü
- & Eric Gouaux
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Letter |
Engineering a memory with LTD and LTP
A rodent study using optogenetics to induce long-term potentiation and long-term depression provides a causal link between synaptic plasticity and memory.
- Sadegh Nabavi
- , Rocky Fox
- & Roberto Malinow
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Article |
Contrasting forms of cocaine-evoked plasticity control components of relapse
Information integration in the nucleus accumbens is commandeered by cocaine at discrete synapses to allow relapse.
- Vincent Pascoli
- , Jean Terrier
- & Christian Lüscher
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Letter |
The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition
The transcription factor NPAS4 enables neurons to distinguish synaptic inputs received at their soma or dendrites; sensory stimulation increases NPAS4 which promotes inhibitory synapses on the soma and destabilizes inhibitory synapses on the dendrites.
- Brenda L. Bloodgood
- , Nikhil Sharma
- & Michael E. Greenberg
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Letter |
Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons
Oxytocin is shown to sharpen neuronal network activity by increasing fast-spiking interneuron activity.
- Scott F. Owen
- , Sebnem N. Tuncdemir
- & Richard W. Tsien
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Letter |
A single pair of interneurons commands the Drosophila feeding motor program
A pair of Drosophila brain cells is identified and its activation alone is found to induce the fly’s complete feeding motor routine when artificially induced; suppressing or ablating these two neurons eliminates the sugar-induced feeding behaviour, but ablation of just one neuron results in asymmetric movements.
- Thomas F. Flood
- , Shinya Iguchi
- & Motojiro Yoshihara
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Article |
LTP requires a reserve pool of glutamate receptors independent of subunit type
The minimal possible requirement for AMPA receptor trafficking during long-term potentiation is explored, revealing that no region of the receptor subunit is necessary, in contrast with previous work; the only requirement for LTP seems to be a large reserve of glutamate receptors.
- Adam J. Granger
- , Yun Shi
- & Roger A. Nicoll
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Letter |
An epigenetic blockade of cognitive functions in the neurodegenerating brain
Histone deacetylase 2 is shown to suppress genes involved in cognitive function epigenetically, potentially opening the door to treatments for Alzheimer’s and other neurodegenerative diseases by developing HDAC2-selective inhibitors.
- Johannes Gräff
- , Damien Rei
- & Li-Huei Tsai
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News & Views |
Reward alters specific connections
How does the brain couple a fleeting sensory input to a delayed reward during learning? A study in locusts shows that coincident firing of neurons can 'mark' a neuronal connection for later modulation. See Article p.47
- Timothy E. Holy
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Article |
Conditional modulation of spike-timing-dependent plasticity for olfactory learning
In the locust olfactory system, spike-timing-dependent plasticity acts as a synaptic ‘tag’ that labels only the synapses active in response to specific odorants, thus priming them for subsequent modulation of the plasticity rule.
- Stijn Cassenaer
- & Gilles Laurent
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News & Views |
Behavioural effects of cocaine reversed
Cocaine use causes lasting changes in behaviour by altering the strength of connections between neurons. The finding that these changes can be reversed in mice suggests strategies that could be used to treat drug addiction. See Letter p.71
- Marina E. Wolf
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Letter |
Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour
In mice, cocaine is found to potentiate excitatory transmission in medium-sized spiny neurons expressing the type-1 dopamine receptor; depotentiation reversed cocaine-induced locomotor sensitization, raising the possibility of novel treatments for addiction.
- Vincent Pascoli
- , Marc Turiault
- & Christian Lüscher
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Article |
Mutations causing syndromic autism define an axis of synaptic pathophysiology
The mutations that underlie the diseases tuberous sclerosis complex and fragile X syndrome produce abnormalities in synaptic plasticity and function that can be corrected by treatments that modulate metabotropic glutamate receptor 5 in opposite directions.
- Benjamin D. Auerbach
- , Emily K. Osterweil
- & Mark F. Bear
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Letter |
Learning-related feedforward inhibitory connectivity growth required for memory precision
- Sarah Ruediger
- , Claudia Vittori
- & Pico Caroni
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Research Highlights |
Omega-3s affect brain signalling
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Brief Communications Arising |
Laurén et al. reply
- Juha Laurén
- , David A. Gimbel
- & Stephen M. Strittmatter
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Brief Communications Arising |
The prion protein as a receptor for amyloid-β
- Helmut W. Kessels
- , Louis N. Nguyen
- & Roberto Malinow
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News & Views |
Brain's traffic lights
The organization of behaviour as sequences of actions requires proper initiation and termination of each action sequence. The neural circuit that signals instructions to start and stop is now revealed.
- Paolo Calabresi
- & Massimiliano Di Filippo
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Letter |
A novel pathway regulates memory and plasticity via SIRT1 and miR-134
The deacetylase SIRT1 has been suggested to function in normal brain physiology, but it is not known whether it participates in higher-order brain functions. These authors demonstrate a role for SIRT1 in synaptic plasticity and memory formation, with activation enhancing synaptic strength and memory formation. These effects were regulated through a post-transcriptional mechanism involving CREB activation and miR-134 production. This interplay represents another mechanism of plasticity regulation with behavioural consequences.
- Jun Gao
- , Wen-Yuan Wang
- & Li-Huei Tsai
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News & Views |
A plastic axonal hotspot
Neurons generate their output signal — the action potential — in a distinct region of the axon called the initial segment. The location and extent of this trigger zone can be modified by neural activity to control excitability.
- Jan Gründemann
- & Michael Häusser
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Letter |
Human memory strength is predicted by theta-frequency phase-locking of single neurons
Although explored in the rodent, the relationship between single neuron activity, oscillations and behavioural learning is unknown in humans. Here, successful memory formation in humans was predicted by the coordination of spike timing relative to the local theta oscillation. These data provide a direct connection between the behavioural modulation of oscillations and plasticity within specific circuits.
- Ueli Rutishauser
- , Ian B. Ross
- & Erin M. Schuman
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Letter |
Long-term potentiation depends on release of d-serine from astrocytes
The involvement of astroglia in long-term potentiation (LTP) of synaptic transmission remains controversial. Clamping internal Ca2+ in individual astrocytes in the CA1 area of the hippocampus is now shown to block LTP induction at nearby excitatory synapses through an effect on the N-methyl-D-aspartate receptor. This LTP blockade can be reversed by exogenous D-serine, normally released in a Ca2+-dependent manner from astrocytes.
- Christian Henneberger
- , Thomas Papouin
- & Dmitri A. Rusakov