Featured
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A body–brain circuit that regulates body inflammatory responses
- Hao Jin
- , Mengtong Li
- & Charles S. Zuker
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Article
| Open Access
A concerted neuron–astrocyte program declines in ageing and schizophrenia
A synaptic neuron and astrocyte program (SNAP) varies among healthy humans, may shape interindividual differences in synapses and plasticity, and is undermined in schizophrenia and with advancing age.
- Emi Ling
- , James Nemesh
- & Steven A. McCarroll
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Article
| Open Access
Alternative splicing of latrophilin-3 controls synapse formation
Latrophilin-3 organizes synapses through a convergent dual-pathway mechanism in which Gαs signalling is activated and phase-separated postsynaptic protein scaffolds are recruited.
- Shuai Wang
- , Chelsea DeLeon
- & Thomas C. Südhof
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Article
| Open Access
Single-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain
Methylome-based clustering and cross-modality integration with companion datasets from the BRAIN Initiative Cell Census Network enabled the construction of a 3D multi-omic genome atlas of the adult mouse brain featuring thousands of cell-type-specific profiles.
- Hanqing Liu
- , Qiurui Zeng
- & Joseph R. Ecker
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Article
| Open Access
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions.
- Zizhen Yao
- , Cindy T. J. van Velthoven
- & Hongkui Zeng
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Article
| Open Access
Single-cell analysis of chromatin accessibility in the adult mouse brain
An atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain unravels the transcriptional regulatory programs that drive the heterogeneity and complexity of brain structure and function.
- Songpeng Zu
- , Yang Eric Li
- & Bing Ren
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Article
| Open Access
Molecularly defined and spatially resolved cell atlas of the whole mouse brain
A comprehensive cell atlas of the whole mouse brain with high molecular and spatial resolution is generated.
- Meng Zhang
- , Xingjie Pan
- & Xiaowei Zhuang
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Article
| Open Access
Disease-specific tau filaments assemble via polymorphic intermediates
A time-resolved cryogenic electron microscopy analysis provides structural information on the processes of primary and secondary nucleation of tau amyloid formation, with implications for the development of new therapies.
- Sofia Lövestam
- , David Li
- & Sjors H. W. Scheres
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Article
| Open Access
m1A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration
TDP-43 binds to N1-methyladenosine on CAG repeat RNA, resulting in the formation of gel-like TDP-43 aggregates in the cytoplasm that resemble those observed in neurological disease pathology.
- Yuxiang Sun
- , Hui Dai
- & Yinsheng Wang
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Review Article |
Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids
Structural studies of amyloid filaments purified from brains of people with neurodegenerative diseases link specific amyloid folds with distinct diseases and provide a basis for the development of models of neurodegenerative disease.
- Sjors H. W. Scheres
- , Benjamin Ryskeldi-Falcon
- & Michel Goedert
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Article
| Open Access
Spatial atlas of the mouse central nervous system at molecular resolution
In situ spatial transcriptomic analysis of more than 1 million cells are used to create a 200-nm-resolution spatial molecular atlas of the adult mouse central nervous system and identify previously unknown tissue architectures.
- Hailing Shi
- , Yichun He
- & Xiao Wang
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Article
| Open Access
A cell-type-specific error-correction signal in the posterior parietal cortex
A molecularly defined subset of somatostatin-positive inhibitory neurons in the mouse posterior parietal cortex carries a cell-type-specific error-correction signal for navigation.
- Jonathan Green
- , Carissa A. Bruno
- & Christopher D. Harvey
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Article
| Open Access
Astrocyte–neuron subproteomes and obsessive–compulsive disorder mechanisms
Analyses of the proteomes of astrocytes and neurons in a cell-specific and subcompartment-specific manner reveal distinct roles for these cell types that are relevant to obsessive–compulsive disorder and perhaps other brain disorders.
- Joselyn S. Soto
- , Yasaman Jami-Alahmadi
- & Baljit S. Khakh
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Article
| Open Access
Essential elements of radical pair magnetosensitivity in Drosophila
Non-CRYPTOCHROME-dependent radical pairs can elicit responses to magnetic fields in neurons in Drosophila melanogaster.
- Adam A. Bradlaugh
- , Giorgio Fedele
- & Richard A. Baines
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Article
| Open Access
A NPAS4–NuA4 complex couples synaptic activity to DNA repair
A neuron-specific activity-dependent DNA repair mechanism is identified, the impairment of which may lead to neurodevelopmental disorders, neurodegeneration and ageing.
- Elizabeth A. Pollina
- , Daniel T. Gilliam
- & Michael E. Greenberg
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Article |
Programmable RNA sensing for cell monitoring and manipulation
RNA sensing-mediated payload expression provides a specific, versatile, simple and generalizable means of detecting and manipulating animal cells with broad potential applications.
- Yongjun Qian
- , Jiayun Li
- & Z. Josh Huang
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Article
| Open Access
Gut–brain circuits for fat preference
Behavioural and genetic experiments in mice reveal gut-to-brain circuits driving the development of fat preference, one responding to intestinal sugar and fat using cholecystokinin signalling, and the other responding only to fat.
- Mengtong Li
- , Hwei-Ee Tan
- & Charles S. Zuker
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Article
| Open Access
Endocytosis in the axon initial segment maintains neuronal polarity
Endocytosis and degradation of plasma membrane proteins in the axon initial segment, together with the diffusion-barrier mechanism, maintain a polarized distribution of plasma membrane proteins in Caenorhabditis elegans, mouse, rat and human neurons.
- Kelsie Eichel
- , Takeshi Uenaka
- & Kang Shen
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Article |
Dual action of ketamine confines addiction liability
Experiments in mice show that although ketamine has positive reinforcement properties, which are driven by its action on the dopamine system, it does not induce the synaptic plasticity that is typically observed with addiction.
- Linda D. Simmler
- , Yue Li
- & Christian Lüscher
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Article |
The gut metabolite indole-3 propionate promotes nerve regeneration and repair
- Elisabeth Serger
- , Lucia Luengo-Gutierrez
- & Simone Di Giovanni
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Article |
Molecularly defined circuits for cardiovascular and cardiopulmonary control
In mouse, two distinct types of neurons from the brainstem nucleus ambiguus, one that innervates the heart and another that innervates both the heart and lung, collectively control cardiac function and coordinate cardiac and pulmonary function.
- Avin Veerakumar
- , Andrea R. Yung
- & Mark A. Krasnow
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Article |
CCR5 closes the temporal window for memory linking
A molecular mechanism involving CCR5 and CCL5 determines the temporal window in which a memory can be linked with subsequent memories, and in aged mice an increase in CCR5 is associated with defects in memory linking.
- Yang Shen
- , Miou Zhou
- & Alcino J. Silva
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Transcriptomic mapping uncovers Purkinje neuron plasticity driving learning
Subpopulations of Purkinje neurons display distinct transcriptomic responses and functions in associative learning.
- Xiaoying Chen
- , Yanhua Du
- & Azad Bonni
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Article
| Open Access
Age-dependent formation of TMEM106B amyloid filaments in human brains
A study using structure determination by cryogenic electron microscopy identifies and characterizes TMEM106B amyloid filaments in human brain, and suggests that their formation is age dependent, with no obvious association with disease.
- Manuel Schweighauser
- , Diana Arseni
- & Sjors H. W. Scheres
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Article |
A global timing mechanism regulates cell-type-specific wiring programmes
Integration of a global temporal transcriptional module with cell-type-specific transcription factors influences neuronal wiring in the fly visual system.
- Saumya Jain
- , Ying Lin
- & S. Lawrence Zipursky
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Article
| Open Access
Mechanisms of inhibition and activation of extrasynaptic αβ GABAA receptors
Cryo-electron microscopy structures are used to identify mechanisms underlying distinct features of extrasynaptic type A γ-aminobutyric acid receptors.
- Vikram Babu Kasaragod
- , Martin Mortensen
- & Paul S. Miller
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Article |
Synthon-based ligand discovery in virtual libraries of over 11 billion compounds
V-SYNTHES, a scalable and computationally cost-effective synthon-based approach to compound screening, identified compounds with a high affinity for CB2 and CB1 in a hierarchical structure-based screen of more than 11 billion compounds.
- Arman A. Sadybekov
- , Anastasiia V. Sadybekov
- & Vsevolod Katritch
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Article |
Exercise plasma boosts memory and dampens brain inflammation via clusterin
Plasma from voluntarily running mice reduces baseline expression of neuroinflammatory genes and experimentally induced brain inflammation when infused into sedentary mice.
- Zurine De Miguel
- , Nathalie Khoury
- & Tony Wyss-Coray
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An endogenous opioid circuit determines state-dependent reward consumption
Studies in mice show that µ-opioid peptide receptor regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection and requires enkephalin-producing neurons.
- Daniel C. Castro
- , Corinna S. Oswell
- & Michael R. Bruchas
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Article
| Open Access
Comparative cellular analysis of motor cortex in human, marmoset and mouse
An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.
- Trygve E. Bakken
- , Nikolas L. Jorstad
- & Ed S. Lein
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Article
| Open Access
A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.
- Zizhen Yao
- , Hanqing Liu
- & Eran A. Mukamel
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Article
| Open Access
Human neocortical expansion involves glutamatergic neuron diversification
Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.
- Jim Berg
- , Staci A. Sorensen
- & Ed S. Lein
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Article
| Open Access
A multimodal cell census and atlas of the mammalian primary motor cortex
The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.
- Edward M. Callaway
- , Hong-Wei Dong
- & Susan Sunkin
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Article |
Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling
A population of hypothalamic dopamine neurons sustains mating drive in male mice through a persistent mode of biochemical signalling in target neurons.
- Stephen X. Zhang
- , Andrew Lutas
- & Mark L. Andermann
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Article |
GluD1 is a signal transduction device disguised as an ionotropic receptor
The ionotropic glutamate delta receptors GluD1 and GluD2 form distinct neurexin–cerebellin complexes that differentially regulate postsynaptic glutamate receptor activities.
- Jinye Dai
- , Christopher Patzke
- & Thomas C. Südhof
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MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration
The natural antisense transcript MAPT-AS1 interferes with translation of mRNA transcript into tau protein in the brain and may represent a general mechanism for controlling levels of intrinsically disordered proteins, with particular relevance for neurodegeneration.
- Roberto Simone
- , Faiza Javad
- & Rohan de Silva
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Neuronal enhancers are hotspots for DNA single-strand break repair
DNA single-strand breaks in neurons accumulate at high levelsin functional enhancers.
- Wei Wu
- , Sarah E. Hill
- & André Nussenzweig
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Article |
Antidepressant actions of ketamine engage cell-specific translation via eIF4E
The antidepressant-like effects of ketamine in mice depend on the expression of specific eIF4E-binding proteins in excitatory and inhibitory neurons.
- Argel Aguilar-Valles
- , Danilo De Gregorio
- & Nahum Sonenberg
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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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A brainstem peptide system activated at birth protects postnatal breathing
A peptidergic brainstem circuit is identified that supports the initiation and establishment of breathing by providing a supplementary respiratory drive immediately after birth.
- Yingtang Shi
- , Daniel S. Stornetta
- & Douglas A. Bayliss
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Article |
The cellular basis of distinct thirst modalities
The authors uncover the diverse transcriptomic cell types of thirst-driving neurons in the lamina terminalis and show that unique combinations of neuron types respond to and mediate distinct thirst states.
- Allan-Hermann Pool
- , Tongtong Wang
- & Yuki Oka
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Amygdala inhibitory neurons as loci for translation in emotional memories
Protein synthesis is required in distinct populations of inhibitory neurons in the mouse amygdala to store memories of danger and safety.
- Prerana Shrestha
- , Zhe Shan
- & Eric Klann
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Matters Arising |
Heat detection by the TRPM2 ion channel
- Bruno Vilar
- , Chun-Hsiang Tan
- & Peter A. McNaughton
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Article |
Distinct subnetworks of the thalamic reticular nucleus
A study integrating single-cell RNA-sequencing and electrophysiology data shows that in mouse, the cellular repertoire of the thalamic reticular nucleus is characterized by a transcriptomic gradient defined at its extremes by mutually exclusive expression of Spp1 and Ecel1, providing insights into the organizational principles underlying the divergent functions of this brain region.
- Yinqing Li
- , Violeta G. Lopez-Huerta
- & Guoping Feng
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A neurotransmitter produced by gut bacteria modulates host sensory behaviour
A neuromodulator produced by commensal Providencia bacteria that colonize the gut of Caenorhabditis elegans mimics the functions of the cognate host molecule to manipulate a sensory decision of the host.
- Michael P. O’Donnell
- , Bennett W. Fox
- & Piali Sengupta
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Structure of a D2 dopamine receptor–G-protein complex in a lipid membrane
The structure of the D2 dopamine receptor in complex with its G protein reveals how dopamine receptors are activated and, importantly, how a G-protein-coupled receptor can interact with its G protein in a phospholipid membrane.
- Jie Yin
- , Kuang-Yui M. Chen
- & Daniel M. Rosenbaum
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Article |
Neurons that regulate mouse torpor
A specific neuronal population in the medial and lateral preoptic area of the hypothalamus regulates entry into torpor in mice.
- Sinisa Hrvatin
- , Senmiao Sun
- & Michael E. Greenberg
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Letter |
The flight response impairs cytoprotective mechanisms by activating the insulin pathway
The release of tyramine during the flight response in nematodes activates the DAF-2/insulin–IGF pathway to downregulate cytoprotective mechanisms and shorten lifespan.
- María José De Rosa
- , Tania Veuthey
- & Mark J. Alkema
Structural pharmacology and therapeutic potential of 5-methoxytryptamines
Magnetic field responses in Drosophila