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Article
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Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes
SNARE-dependent membrane fusion underlies neurotransmission in the nervous system. Here, the authors demonstrate how, in mammalian neurons, the synaptic protein tomosyn controls secretion by increasing the energy barrier for fusion.
- Marieke Meijer
- , Miriam Öttl
- & Matthijs Verhage
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Article
| Open Access
Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles
How synaptic vesicles (SVs) are clustered at the presynapse is suggestive of anchoring processes counteracting their diffusion. Here, the authors co-track recycling and reserve SVs in live neurons to find that Synapsin 2a tetramerization dynamically immobilizes reserve SVs at the presynapse.
- Shanley F. Longfield
- , Rachel S. Gormal
- & Frédéric A. Meunier
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Article
| Open Access
Distinct neurochemical influences on fMRI response polarity in the striatum
The relationship between striatal vascular and neural activity is not fully understood. Here the authors found neuronal activity inadequately explains striatal hemodynamic polarity, challenging classic fMRI interpretations.
- Domenic H. Cerri
- , Daniel L. Albaugh
- & Yen-Yu Ian Shih
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Article
| Open Access
Specification of neural circuit architecture shaped by context-dependent patterned LAR-RPTP microexons
LAR-RPTPs are presynaptic cell-adhesion proteins that regulate the synaptic properties. Here, LAR-RPTP microexon expression is profiled in region-, cell-type- and circuit-specific contexts and its physiological significance in encoding synaptic architecture is demonstrated.
- Kyung Ah Han
- , Taek-Han Yoon
- & Jaewon Ko
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Article
| Open Access
A presynaptic source drives differing levels of surround suppression in two mouse retinal ganglion cell types
Compartments of neurons can sometimes act as independent computational units. Here the authors show that retinal bipolar cells, some of the smallest mammalian neurons, send different signals to downstream ganglion cells via different synapses.
- David Swygart
- , Wan-Qing Yu
- & Gregory W. Schwartz
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Article
| Open Access
The juxtamembrane linker of synaptotagmin 1 regulates Ca2+ binding via liquid-liquid phase separation
Synaptotagmin (syt) 1 is a calcium sensor for neuronal exocytosis. Here, the authors show that the juxtamembrane linker of this integral membrane protein negatively regulates its calcium sensing activity by mediating self-association via liquid-liquid phase separation.
- Nikunj Mehta
- , Sayantan Mondal
- & Edwin R. Chapman
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Perspective
| Open Access
Membrane transformations of fusion and budding
Life-crucial membrane fusion and budding were traditionally viewed with electron microscopy. With recent breakthroughs that visualize membrane transformation in real time, Wu and Chan synthesize a new model with mechanistic principles and functions.
- Ling-Gang Wu
- & Chung Yu Chan
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Article
| Open Access
Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration
Synaptotagmin-1 and -7 are calcium sensors that distinctly drive vesicular exocytosis. Here, using wild-type proteins but manipulating the composition of the target membranes, the authors show that synaptotagmin-7 is unusually robust at penetrating membranes.
- Kevin C. Courtney
- , Taraknath Mandal
- & Edwin R. Chapman
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Article
| Open Access
Complex 33-beam simulated galactic cosmic radiation exposure impacts cognitive function and prefrontal cortex neurotransmitter networks in male mice
Here the authors show in male mice that acute and chronic complex simulated galactic cosmic radiation exposure differentially reorganized prefrontal cortex neurotransmitter networks in vivo, which was associated with cognitive deficits.
- Rajeev I. Desai
- , Brian D. Kangas
- & Charles L. Limoli
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Article
| Open Access
Tau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles
Using single-molecule super-resolution microscopy, researchers revealed that Tau controls the recycling pool of synaptic vesicles in hippocampal neurons by forming nanoscale biomolecular condensates that are dynamically regulated by neuronal activity.
- Shanley F. Longfield
- , Mahdie Mollazade
- & Ramón Martínez-Mármol
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Article
| Open Access
Selective plasticity of fast and slow excitatory synapses on somatostatin interneurons in adult visual cortex
Excitatory synapses on somatostatin sensory neurons in the cortex are not fully characterised. Here the authors report that visual cortex somatostatin neurons are regulated by sensory experience by utilizing two distinct types of excitatory synapses.
- Bryce D. Grier
- , Samuel Parkins
- & Hey-Kyoung Lee
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Article
| Open Access
Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease
Neurotransmitter receptor distributions help explain structural and functional brain alterations in Parkinson’s disease. Distinct multi-receptor profiles are associated with the severity of motor, and visuospatial, psychiatric and memory symptoms.
- Ahmed Faraz Khan
- , Quadri Adewale
- & Yasser Iturria-Medina
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Article
| Open Access
Reversal of cell, circuit and seizure phenotypes in a mouse model of DNM1 epileptic encephalopathy
One third of all epilepsies are treatment-resistant. Here, the authors show in a genetic model of epilepsy that a repurposed drug can correct cell defects, brain circuits and seizure-like events by accelerating endocytosis.
- Katherine Bonnycastle
- , Katharine L. Dobson
- & Michael A. Cousin
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Article
| Open Access
Neurexin-3 subsynaptic densities are spatially distinct from Neurexin-1 and essential for excitatory synapse nanoscale organization in the hippocampus
How do individual neurexins control distinct synaptic properties? Here, the authors show that the nanoscopic properties of Nrxn1 and Nrxn3 are spatially discrete and propose a model where Nrxn1 and Nrxn3 signal in parallel to control synapse function.
- Brian A Lloyd
- , Ying Han
- & Jason Aoto
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Article
| Open Access
Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death in Drosophila
Neuronal death is a feature of development and neurodegeneration. Here, the authors report that ablation of Drosophila motor neurons triggers Draper-dependent signaling in glia to engage ‘cross-neuron plasticity’ in bystander neurons.
- Yupu Wang
- , Ruiling Zhang
- & Robert A. Carrillo
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Article
| Open Access
Mechanisms of simultaneous linear and nonlinear computations at the mammalian cone photoreceptor synapse
Cone photoreceptors signal to several bipolar cell types at one of the most structurally complex synapses in the central nervous system. Here, the authors show how the 3D organization of this synapse creates different signals in the postsynaptic OFF bipolar cell types.
- Chad P. Grabner
- , Daiki Futagi
- & Steven H. DeVries
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Article
| Open Access
The monoaminergic system is a bilaterian innovation
Monoamines act as neuromodulators in the nervous system, but their evolutionary origins are unclear. Here, the authors examine the evolution of genes involved in monoamine production, and processing suggesting that the monoaminergic system evolved in the bilaterian stem-group.
- Matthew Goulty
- , Gaelle Botton-Amiot
- & Roberto Feuda
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Article
| Open Access
Afferent convergence to a shared population of interneuron AMPA receptors
Glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. Here, the authors find in the cerebellar cortex that glutamate spillover from climbing fibers activates synaptic AMPA receptors of molecular layer interneurons, allowing glutamate from an unconnected pathway to co-opt postsynaptic receptors.
- Reagan L. Pennock
- , Luke T. Coddington
- & Jacques I. Wadiche
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Article
| Open Access
Homeostatic synaptic plasticity rescues neural coding reliability
How synaptic plasticity affects neural coding reliability is not well understood. Here, the authors find that reducing neurotransmitter release probability triggers a homeostatic compensation to maintain neural coding and behavioral reliability.
- Eyal Rozenfeld
- , Nadine Ehmann
- & Moshe Parnas
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Article
| Open Access
Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis
The authors describe the mechanism of exo-endocytosis coupling at synapses. They find that actin forms a ring around the region of exocytosis. This ring conserves membrane area, allowing induction of inward membrane buckling following exocytosis.
- Tyler H. Ogunmowo
- , Haoyuan Jing
- & Jian Liu
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Article
| Open Access
Vesicular glutamate transporters are H+-anion exchangers that operate at variable stoichiometry
In glutamatergic neurons, synaptic vesicles contain glutamate, but not aspartate. Here, the authors show that vesicular glutamate transporters are H+/anion exchangers that attain high selectivity for glutamate via variable transport coupling.
- Bettina Kolen
- , Bart Borghans
- & Christoph Fahlke
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Article
| Open Access
Parabolic avalanche scaling in the synchronization of cortical cell assemblies
The diversity of synchronized neuronal groups provides a challenge for brain theories. Here, the authors report that group size grows quadratically with duration in line with predictions for neuronal avalanches and brain dynamics being critical.
- Elliott Capek
- , Tiago L. Ribeiro
- & Dietmar Plenz
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Article
| Open Access
Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43
Cannabis impacts our brain by engaging the CB1 receptor. Here, the authors identify a protein called GAP43 that interacts with CB1 and blocks its synaptic functions. This finding provides a conceptual view to understand how CB1 acts in the brain.
- Irene B. Maroto
- , Carlos Costas-Insua
- & Manuel Guzmán
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Article
| Open Access
A combinatorial code of neurexin-3 alternative splicing controls inhibitory synapses via a trans-synaptic dystroglycan signaling loop
The presynaptic release probability is a major determinant of synaptic transmission in brain. Here, the authors show that a trans-synaptic signaling complex comprising presynaptic Neurexin-3 and postsynaptic dystroglycan controls the release probability of diverse inhibitory synapses.
- Justin H. Trotter
- , Cosmos Yuqi Wang
- & Thomas C. Südhof
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Article
| Open Access
Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons in male mice
Little is known about the synaptic organization of associative cortical structures such as the medial prefrontal cortex. Here, the authors use two-photon optogenetic stimulation to obtain a detailed cellular resolution map of functional synaptic connectivity of the mouse medial prefrontal cortex, finding unique spatial patterns of local-circuit connectivity in neurons that project to the basolateral amygdala.
- Yoav Printz
- , Pritish Patil
- & Ofer Yizhar
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Article
| Open Access
Two gates mediate NMDA receptor activity and are under subunit-specific regulation
NMDA receptors are glutamate-gated ion channels that regulate fast signaling in the brain. Here, the authors show that the opening and closing patterns of the channel derive from the action of two gates that are regulated by distinct subunits.
- Johansen B. Amin
- , Miaomiao He
- & Lonnie P. Wollmuth
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Article
| Open Access
UNC-43/CaMKII-triggered anterograde signals recruit GABAARs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs
The pre-and postsynaptic communication is critical for faithful synaptic transmission and induction of synaptic plasticity. Here, the authors found that CaMKII functions at GABAergic neurons to recruit GABAARs by triggering anterograde signals.
- Yue Hao
- , Haowen Liu
- & Xia-Jing Tong
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Article
| Open Access
Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions
LRRTM1 is a post synaptic adhesion protein, that promotes AMPA receptor mediated synaptic transmission. Here the authors show that LRRTM1 and the adhesion molecule SynCAM 1 act together to organize synapses in the prefrontal cortex with relevance for cognitive function in mice.
- Karen Perez de Arce
- , Adema Ribic
- & Thomas Biederer
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Article
| Open Access
mGluR5 is transiently confined in perisynaptic nanodomains to shape synaptic function
The subsynaptic organization of group I mGluRs modulates their activation and downstream signaling, essential for synaptic transmission and plasticity. Here, the authors describe how the C-terminal domain of mGluR5 controls its dynamic organization in perisynaptic nanodomains, and prevents mGluR5 form entering the synapse, allowing mGluR5 to finely tune synaptic signalling.
- Nicky Scheefhals
- , Manon Westra
- & Harold D. MacGillavry
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Article
| Open Access
Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles
Existing optogenetic silencing methods affect membrane potential, biochemistry or protein integrity. Here, the authors demonstrate an approach for silencing synaptic transmission that combines fast activation and reversibility, by using nondisruptive, reversible, light-evoked clustering of synaptic vesicles, which they validate in Caenorhabditis elegans, zebrafish, and murine cell culture.
- Dennis Vettkötter
- , Martin Schneider
- & Alexander Gottschalk
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Article
| Open Access
A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling
Presynaptic homeostatic plasticity adaptively enhances neurotransmitter release following diminished postsynaptic glutamate receptor functionality. Here the authors identify a calcium-independent signaling system where active CaMKII detects a short domain encoded in a glutamate receptor C-tail, which gates retrograde homeostatic communication at a model glutamatergic synapse.
- Sarah Perry
- , Yifu Han
- & Dion Dickman
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Article
| Open Access
Vesicular release probability sets the strength of individual Schaffer collateral synapses
It is not fully understood if the probability of synaptic vesicle release is homogenous or varies between individual boutons. Here the authors perform optical quantal analyses of individual Schaffer collateral synapses, showing that multivesicular release enables a tenfold increase in glutamate output and that the vesicular release probability is not uniform between synapses.
- Céline D. Dürst
- , J. Simon Wiegert
- & Thomas G. Oertner
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Article
| Open Access
SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice
The protein SLITRK2 plays an important role in synaptic communication. This study identifies X-linked SLITRK2 variants that underlie neurodevelopmental disorders by impairing excitatory synapses.
- Salima El Chehadeh
- , Kyung Ah Han
- & Ji Won Um
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Article
| Open Access
Asynchronous glutamate release is enhanced in low release efficacy synapses and dispersed across the active zone
Neurotransmitters can be released with a delay in relation to action potentials. This work demonstrates how this asynchronous release is related to overall vesicle release probability and short-term plasticity.
- Philipe R. F. Mendonça
- , Erica Tagliatti
- & Kirill E. Volynski
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Article
| Open Access
A synaptomic analysis reveals dopamine hub synapses in the mouse striatum
The neurotransmitter dopamine is an important regulator of brain function. Here the authors describe “dopamine hub synapses”, where dopamine transmission may act in synergy with other neurotransmitters.
- Vincent Paget-Blanc
- , Marlene E. Pfeffer
- & Etienne Herzog
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Article
| Open Access
Induction of synapse formation by de novo neurotransmitter synthesis
Neuronal communication relies on matching different neurostransmitter types with their appropriate receptors. The authors here demonstrate that release of a novel neurotransmitter from presynaptic terminals can induce both the accumulation and activation of its corresponding receptors on postsynaptic neurons.
- Scott R. Burlingham
- , Nicole F. Wong
- & Soham Chanda
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Article
| Open Access
Diurnal changes in the efficiency of information transmission at a sensory synapse
Neuromodulators can adjust how sensory signals are processed. In this study, the authors demonstrate how time of day affects the way information is transmitted in the zebrafish retina.
- José Moya-Díaz
- , Ben James
- & Leon Lagnado
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Article
| Open Access
Nanoscale rules governing the organization of glutamate receptors in spine synapses are subunit specific
Glutamate receptors comprise two obligate subunits and two subunits that confer distinct properties and functions to the specific tetramers, which also localize to distinct synaptic spines. Here, the authors use STimulated Emission Depletion nanoscopy (STED) to provide detailed insights into the spatial organization of glutamate receptor types.
- Martin Hruska
- , Rachel E. Cain
- & Matthew B. Dalva
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Article
| Open Access
Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats
The effects of SAP97 mutations associated with schizophrenia on synaptic function are unclear. Here, the authors show that schizophrenia-related SAP97 mutations enhance glutamatergic synapse strength in the dentate gyrus, impairing contextual episodic memory in rats.
- Yuni Kay
- , Linda Tsan
- & Bruce E. Herring
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Article
| Open Access
Physiological synaptic activity and recognition memory require astroglial glutamine
The authors present a fluorescent probe that tracks glutamine in live cells. They demonstrate the capabilities of the probe by providing direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions.
- Giselle Cheung
- , Danijela Bataveljic
- & Nathalie Rouach
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Article
| Open Access
Determinants of synapse diversity revealed by super-resolution quantal transmission and active zone imaging
Super-resolution quantal imaging relates transmission at excitatory synapses to presynaptic molecular composition. The authors find that evoked transmission varies greatly between synapses and is uncorrelated and physically separate from spontaneous transmission, and identify responsible presynaptic proteins.
- Zachary L. Newman
- , Dariya Bakshinskaya
- & Ehud Y. Isacoff
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Article
| Open Access
Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R
Synapses are surrounded by an extracellular matrix (ECM) of extremely long-lived proteins that is thought to only be remodeled by proteolysis and de novo synthesis. Here, the authors show an alternative molecular recycling mechanism that occurs for the key ECM protein Tenascin-R.
- Tal M. Dankovich
- , Rahul Kaushik
- & Silvio O. Rizzoli
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Article
| Open Access
Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit
The authors describe a vesicular transporter, VST-1, that is required in glutamatergic chemosensory neurons for chemotactic avoidance behavior in C. elegans. VST-1 antagonizes VGLUT-dependent packaging of glutamate into synaptic vesicles and determines the strength of synaptic glutamate signaling.
- Jung-Hwan Choi
- , Lauren Bayer Horowitz
- & Niels Ringstad
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Article
| Open Access
CDH2 mutation affecting N-cadherin function causes attention-deficit hyperactivity disorder in humans and mice
Molecular mechanisms of attention-deficit hyperactivity disorder (ADHD) are not fully understood. Here the authors demonstrate a mutation in CDH2, encoding N-cadherin, that is associated with ADHD, and in a mouse model, delineate molecular electrophysiological characteristics associated with this mutation.
- D. Halperin
- , A. Stavsky
- & O. S. Birk
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Article
| Open Access
Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells
The authors show that graded molecular heterogeneity in metabotropic pathways underlies a continuum of temporal responses in cerebellar unipolar brush cells (UBCs). This allows the UBC population to serve as a cell-autonomous basis for temporal integration and learning over multiple time scales.
- Chong Guo
- , Vincent Huson
- & Wade G. Regehr
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Article
| Open Access
Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
In this study, acetylcholine release is shown to reorganise hippocampal CA1 inhibitory networks resulting in prioritisation of entorhinal input over CA3 input. This is achieved by activation of a combination of M3 and M4 muscarinic receptors.
- Jon Palacios-Filardo
- , Matt Udakis
- & Jack R. Mellor
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Article
| Open Access
Excitatory synapses and gap junctions cooperate to improve Pv neuronal burst firing and cortical social cognition in Shank2-mutant mice
How NMDAR and GABA neuronal dysfunctions result in impaired social behaviour is unclear. Here, the authors show that NMDARs and gap junctions in cortical PV interneurons modulate burst firing, affecting social behaviour.
- Eunee Lee
- , Seungjoon Lee
- & Eunjoon Kim
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Article
| Open Access
AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions
Changes in AMPAR localization can control the strength of synaptic transmission. Here, the authors show that the interactions of TARP γ8 and the AMPAR N-terminal domain work together to regulate receptor accumulation and positioning at the post-synapse of mouse hippocampal CA1 neurons.
- Jake F. Watson
- , Alexandra Pinggera
- & Ingo H. Greger
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Article
| Open Access
A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo
Engineering de novo synapse-like connections between neurons could enhance our understanding of neuronal circuits and how they generate behaviour. The authors present a two-component system that creates synthetic neuromodulatory connections to manipulate intracellular Ca2+ levels in in vivo neural circuits.
- Josh D. Hawk
- , Elias M. Wisdom
- & Daniel A. Colón-Ramos
Intracellular magnesium optimizes transmission efficiency and plasticity of hippocampal synapses by reconfiguring their connectivity