Molecular neuroscience articles within Nature

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  • Article |

    RNA-sequencing analysis of cells in the human cortex enabled identification of diverse cell types, revealing well-conserved architecture and homologous cell types as well as extensive differences when compared with datasets covering the analogous region of the mouse brain.

    • Rebecca D. Hodge
    • , Trygve E. Bakken
    •  & Ed S. Lein

  • Article |

    Single-cell transcriptomics from 48 individuals with varying degrees of Alzheimer’s disease pathology demonstrates that gene-expression changes in Alzheimer’s disease are both cell-type specific and shared, and that transcriptional responses show sexual dimorphism.

    • Hansruedi Mathys
    • , Jose Davila-Velderrain
    •  & Li-Huei Tsai

  • Letter |

    Clustered protocadherin ectodomains spontaneously assemble to form a zipper-like lattice of alternating cis and trans interactions at membrane contact sites, which probably represents their mode of function in neuronal self-recognition.

    • Julia Brasch
    • , Kerry M. Goodman
    •  & Lawrence Shapiro

  • Letter |

    A high-resolution X-ray structure and molecular dynamics simulations of the N-methyl-d-aspartate receptor in complexes with channel-blocking ligands reveals the molecular basis of the ligand binding and channel block.

    • Xianqiang Song
    • , Morten Ø. Jensen
    •  & Eric Gouaux

  • Letter |

    Three transient receptor potential channels (TRPA1, TRPV1 and TRPM3) mediate sensitivity to acute noxious heat in mice in a redundant system; mice lacking all three show severe deficits in heat sensing, whereas double-knockout mice do not.

    • Ine Vandewauw
    • , Katrien De Clercq
    •  & Thomas Voets

  • Letter |

    The structure of huntingtin in complex with an interactor is determined to an overall resolution of 4 Å, paving the way for improved understanding of the cellular functions of this protein.

    • Qiang Guo
    • , Bin Huang
    •  & Stefan Kochanek

  • Letter |

    Experimental evidence that global Kctd13 reduction leads to increased RhoA levels that reduce synaptic transmission, implicating RhoA as a potential therapeutic target for neuropsychiatric disorders associated with copy-number variants that include KCTD13.

    • Christine Ochoa Escamilla
    • , Irina Filonova
    •  & Craig M. Powell

  • Article |

    High-resolution structures of the thermostabilized human excitatory amino acid transporter EAAT1, alone or in association with its substrate or small molecule inhibitors, reveal architectural features of human SLC1 transporters and an allosteric mechanism of inhibition.

    • Juan C. Canul-Tec
    • , Reda Assal
    •  & Nicolas Reyes

  • Article |

    Detection of weak electrical signals by skates relies on functional coupling of specific calcium and potassium channels, which mediates oscillations in electrosensory cell membrane voltage.

    • Nicholas W. Bellono
    • , Duncan B. Leitch
    •  & David Julius

  • Article |

    Mouse models of Alzheimer’s disease show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline; driving neurons to oscillate at gamma frequency (40 Hz) reduces levels of amyloid-β peptides.

    • Hannah F. Iaccarino
    • , Annabelle C. Singer
    •  & Li-Huei Tsai

  • Review Article |

    This Review discusses current knowledge of the structure, function and interactions of the metabotropic glutamate and GABAB receptors and the potential to target receptor subunits for future therapeutic intervention in neurological and mental health disorders.

    • Jean-Philippe Pin
    •  & Bernhard Bettler

  • Letter |

    Cannabinoids affect CB1 receptors on the mitochondrial membranes in the brain, triggering a decrease in downstream cAMP-dependent signalling; this leads to a decrease in brain mitochondrial activity and to cannabinoid-induced amnesia.

    • Etienne Hebert-Chatelain
    • , Tifany Desprez
    •  & Giovanni Marsicano

  • Letter |

    In the neocortex, sensory information flows into areas specific for a particular modality through parallel thalamocortical circuits, consisting of first order and higher order nuclei connecting to primary and secondary cortical areas, respectively; here, the authors identify common developmental genetic programs that organize these conserved features in parallel sensory pathways.

    • Laura Frangeul
    • , Gabrielle Pouchelon
    •  & Denis Jabaudon

  • Letter |

    The neuronal mechanism for the detection of non-painful warm stimuli has remained unclear; mammalian TRPM2 ion channel is shown to be required for warmth detection in the non-noxious range of 33–38 °C, and surprisingly to mediate responses to warmth in the autonomic nervous system.

    • Chun-Hsiang Tan
    •  & Peter A. McNaughton

  • Article |

    A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

    • Trygve E. Bakken
    • , Jeremy A. Miller
    •  & Ed S. Lein

  • Letter |

    People infected with West Nile virus often experience cognitive side effects including memory loss through unknown mechanisms; mice and humans infected with the virus experience a loss in hippocampal presynaptic terminals, which can be reversed by disrupting complement or microglia in mice.

    • Michael J. Vasek
    • , Charise Garber
    •  & Robyn S. Klein

  • Article |

    The peptidergic neuronal circuit controlling sigh generation has been identified as ~200 Nmb- or Grp-expressing neurons in the RTN/pFRG breathing control centre of the medulla that project to ~200 receptor-expressing neurons in the respiratory rhythm generator, the preBötzinger Complex.

    • Peng Li
    • , Wiktor A. Janczewski
    •  & Jack L. Feldman

  • Letter |

    A new pathway for the processing of β-amyloid precursor protein (APP) is described in which η-secretase activity, in part mediated by the MT5-MMP metalloproteinase, cleaves APP, and further processing by ADAM10 and BACE1 generates proteolytic fragments capable of inhibiting long-term potentiation in the hippocampus.

    • Michael Willem
    • , Sabina Tahirovic
    •  & Christian Haass

  • Letter |

    The mouse retinal ganglion cell type known as the W3B-RGC, which detects motion of objects against a moving background, is shown to receive strong specific and excitatory input from amacrine cells expressing vesicular glutamine transporter 3; this selective connection is mediated by homophilic interactions of the recognition molecule sidekick 2 (Sdk2), which is expressed on both cells, and disruption of this connection affects object motion detection in W3B-RGCs.

    • Arjun Krishnaswamy
    • , Masahito Yamagata
    •  & Joshua R. Sanes

  • Letter |

    Highly conserved recursive splice sites are identified in vertebrates, particularly within long genes encoding proteins that are involved in neuronal development; analysis of the splicing mechanism reveals that such recursive splicing sites can be used to dictate different mRNA isoforms.

    • Christopher R. Sibley
    • , Warren Emmett
    •  & Jernej Ule

  • Article |

    Here β-catenin, which has been implicated in neurological and psychiatric diseases, including depression, is shown to mediate resilience to chronic stress in mice through induction of Dicer and microRNAs in nucleus accumbens, a key brain reward region.

    • Caroline Dias
    • , Jian Feng
    •  & Eric J. Nestler

  • Letter |

    Two presynaptically secreted isoforms of the protein Punctin in the nematode Caenorhabditis elegans determine the postsynaptic accumulation of acetylcholine versus GABA receptors, raising the question of whether the related human punctin-2 gene, which has been associated with schizophrenia, may also control synaptic organization.

    • Bérangère Pinan-Lucarré
    • , Haijun Tu
    •  & Jean-Louis Bessereau

  • Article |

    Sexual experience brings radical changes in how male mice behave with pups—virgin males attack them whereas mature fathers display parental care; here the authors identify a subset of hypothalamic neurons whose ablation leads to parental deficits in both males and females, and whose activation in virgin males suppresses aggression and induces pup grooming.

    • Zheng Wu
    • , Anita E. Autry
    •  & Catherine G. Dulac

  • Outlook |

    The more we study the genetics of schizophrenia, says Steven E. Hyman, the more daunting — and exciting — are the challenges we see ahead.

    • Steven E. Hyman

  • Article |

    Cervical propriospinal neurons (PNs) form a genetically accessible subclass of V2a interneurons that convey both premotor output and precerebellar copy signals; their ablation in mice impairs reaching movements selectively, and activation of their internal copy projection recruits a rapid cerebellar feedback loop that modulates forelimb movement.

    • Eiman Azim
    • , Juan Jiang
    •  & Thomas M. Jessell

  • Article |

    Mouse and human studies reveal that incorrect gene dosage of SHANK3 (a gene linked to some human neuropsychiatric disorders, including autism spectrum disorder) is associated with behavioural abnormalities including mania, possibly because of actin regulation problems in excitatory/inhibitory synapses.

    • Kihoon Han
    • , J. Lloyd Holder Jr
    •  & Huda Y. Zoghbi

  • Letter |

    After previously discovering that the ion channel TRPA1 is used as an internal temperature sensor in Drosophila to control the slow response of flies to shallow thermal gradients, the authors show here that the rapid response of flies to steep warming gradients relies on a different protein, GR28B, providing the first example of a thermosensory role for a gustatory receptor.

    • Lina Ni
    • , Peter Bronk
    •  & Paul A. Garrity

  • Letter |

    Rett syndrome is caused by mutations in MeCP2, and this study identifies a site on MeCP2, T308, whose phosphorylation is regulated by neuronal activity: phosphorylation of T308 blocks the interaction of MeCP2 with the NCoR co-repressor complex, suppressing MeCP2's ability to repress transcription, and mice carrying mutations of MeCP2 T308 show Rett-syndrome-related symptoms.

    • Daniel H. Ebert
    • , Harrison W. Gabel
    •  & Michael E. Greenberg

  • Article |

    High-resolution imaging has traditionally required thin sectioning, a process that disrupts long-range connectivity in the case of brains: here, intact mouse brains and human brain samples have been made fully transparent and macromolecule permeable using a new method termed CLARITY, which allows for intact-tissue imaging as well as repeated antibody labelling and in situ hybridization of non-sectioned tissue.

    • Kwanghun Chung
    • , Jenelle Wallace
    •  & Karl Deisseroth

  • Letter |

    The membrane protein TMC-1 is required for salt avoidance behaviour in C. elegans, functions as an ion channel directly activated by NaCl in vitro and is a candidate salt chemosensor; the human homologue of TMC-1 is linked to deafness and may be the cochlear hair-cell mechanotransduction channel.

    • Marios Chatzigeorgiou
    • , Sangsu Bang
    •  & William R. Schafer

  • Letter |

    The neuropeptide corticotropin-releasing factor (CRF) acts in the nucleus accumbens of mice to increase dopamine release through coactivation of CRF receptor 1 (CRFR1) and CRFR2, but exposure to severe stress results in loss of this regulation and a switch in the reaction to CRF from appetitive to aversive.

    • Julia C. Lemos
    • , Matthew J. Wanat
    •  & Paul E. M. Phillips

  • Article |

    Heat stroke triggers necrotic cell death and neurodegeneration in Caenorhabditis elegans, but hormetic preconditioning at a mildly elevated temperature strongly protects C. elegans from necrosis induced by several insults, including heat, and shields mammalian neurons from heat cytotoxicity, suggesting that this protective mechanism is conserved.

    • Nikos Kourtis
    • , Vassiliki Nikoletopoulou
    •  & Nektarios Tavernarakis

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