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News and Views

Showing transmitters the door: synucleins accelerate vesicle release pp629 - 631

Dennis J Selkoe

doi:10.1038/nn.4551

α-Synuclein is present at high levels in all neurons and their synapses. We now learn that this protein helps dilate the fusion pore, which forms transiently during vesicle exocytosis, promoting release of certain neurotransmitters.

See also: Article by Logan et al.


Upstream current for a downstream flow pp631 - 633

Jessica A Filosa

doi:10.1038/nn.4542

Capillary endothelial cells sense neuronal activity-evoked increases in extracellular K+ via KIR2.1 inwardly rectifying K+ channels. The ensuing hyperpolarization travels upstream along the vascular network, reaching arterioles and evoking vasodilation.

See also: Article by Longden et al.


Cerebellar granule cells expand their talents pp633 - 634

Matthew I Becker & Abigail L Person

doi:10.1038/nn.4552

Technical advances in calcium imaging enable the first tests of classic theories of cerebellar learning. Two independent groups reveal dense representation of surprising modalities in cerebellar granule cells.

See also: Article by Giovannucci et al.


Monkeys face face distortions pp635 - 636

Guy A Orban

doi:10.1038/nn.4556

A study combines monkey behavioral testing with electrical stimulation of face patches, located with functional MRI and studied electrophysiologically, to probe the behavioral relevance of the face patches' selectivity.

See also: Article by Moeller et al.


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Review

Cell transplantation therapy for spinal cord injury pp637 - 647

Peggy Assinck, Greg J Duncan, Brett J Hilton, Jason R Plemel & Wolfram Tetzlaff

doi:10.1038/nn.4541

The consequences of spinal cord injury are often severe and irreversible; cell transplantation has emerged as a potential treatment. In this Review, the authors highlight mechanisms through which cell transplantation is thought to promote functional improvements and the obstacles to making cell transplantation a viable therapy.


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Articles

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice pp648 - 660

The HD iPSC Consortium

doi:10.1038/nn.4532

The Huntington's disease (HD) induced pluripotent stem cell (iPSC) consortium describe the combined use of differentiated patient-derived iPSCs and systems biology to discover underlying mechanisms in HD. They identify neurodevelopmental deficits in HD cells that can be corrected in cells and in vivo with a small molecule.


Purine synthesis promotes maintenance of brain tumor initiating cells in glioma pp661 - 673

Xiuxing Wang, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C Mack, Yu Shi, Leo J Y Kim, Briana C Prager, William A Flavahan, Xiaojing Liu, Meromit Singer, Christopher G Hubert, Tyler E Miller, Wenchao Zhou, Zhi Huang, Xiaoguang Fang, Aviv Regev, Mario L Suvà, Tae Hyun Hwang, Jason W Locasale, Shideng Bao & Jeremy N Rich

doi:10.1038/nn.4537

Brain tumor initiating cells (BTICs) utilize high-affinity glucose uptake, which is normally active in neurons to maintain energy demands and self-renew. Leveraging metabolomic and genomic analyses, Wang et al. report that de novo purine biosynthesis reprograms BTIC metabolism, revealing a potential point of fragility amenable to targeted cancer therapy.


Regulatory T cells promote myelin regeneration in the central nervous system pp674 - 680

Yvonne Dombrowski, Thomas O'Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, George Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard Perbal, Anna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin & Denise C Fitzgerald

doi:10.1038/nn.4528

Regeneration of myelin is a dynamic, yet enigmatic process. Dombrowski et al. uncover a central role for regulatory T (Treg) cells in driving oligodendrocyte differentiation, in part via CCN3, a novel factor in Treg function and oligodendrocyte biology. This identifies Treg cells as key cellular players in efficient remyelination.


α-Synuclein promotes dilation of the exocytotic fusion pore pp681 - 689

Todd Logan, Jacob Bendor, Chantal Toupin, Kurt Thorn & Robert H Edwards

doi:10.1038/nn.4529

The authors used knockout mice to demonstrate the normal function of the protein α-synuclein, which has a central role in Parkinson's and other neurodegenerative diseases. The presynaptic protein promoted dilation of the exocytotic fusion pore, and mutations that cause Parkinson's disease specifically impaired this normal function.

See also: News and Views by Selkoe


Activity-induced histone modifications govern Neurexin-1 mRNA splicing and memory preservation pp690 - 699

Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie & Ji-Song Guan

doi:10.1038/nn.4536

Relatively little is known about the mechanisms that preserve memories during long-term storage. The authors found that neural activation during learning triggers long-lasting transcription of a specific neurexin-1 splice isoform, enabling retention of hippocampus-dependent memory. This process was mediated by signaling through the AMPK pathway leading to histone modifications.


C1 neurons mediate a stress-induced anti-inflammatory reflex in mice pp700 - 707

Chikara Abe, Tsuyoshi Inoue, Mabel A Inglis, Kenneth E Viar, Liping Huang, Hong Ye, Diane L Rosin, Ruth L Stornetta, Mark D Okusa & Patrice G Guyenet

doi:10.1038/nn.4526

Acute stress elicits physiological and behavioral responses that enhance survival. This study in mice shows that stress reduces tissue injury in a model of renal ischemia-reperfusion injury by activating an anti-inflammatory response via the sympathetic system and the spleen. C1 neurons located in the brainstem mediate this protective effect of stress.


GLP-1 acts on habenular avoidance circuits to control nicotine intake pp708 - 716

Luis M Tuesta, Zuxin Chen, Alexander Duncan, Christie D Fowler, Masago Ishikawa, Brian R Lee, Xin-An Liu, Qun Lu, Michael Cameron, Matthew R Hayes, Theodore M Kamenecka, Matthew Pletcher & Paul J Kenny

doi:10.1038/nn.4540

Nicotine has rewarding effects that motivate its consumption. In addition to these rewarding effects, nicotine also has aversive properties that motivate its avoidance. Here the authors identify a pathway in the brain that regulates nicotine avoidance. Adaptive responses in this and other aversion-related pathways may contribute to the development of tobacco addiction.


Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow pp717 - 726

Thomas A Longden, Fabrice Dabertrand, Masayo Koide, Albert L Gonzales, Nathan R Tykocki, Joseph E Brayden, David Hill-Eubanks & Mark T Nelson

doi:10.1038/nn.4533

Longden et al. demonstrate that brain capillaries function as a vast sensory web, monitoring neuronal activity by sensing K+ and translating this into a KIR-channel-mediated regenerative retrograde hyperpolarizing signal that propagates to upstream arterioles to drive vasodilation and an increase in blood flow into the capillary bed.

See also: News and Views by Filosa


Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning pp727 - 734

Andrea Giovannucci, Aleksandra Badura, Ben Deverett, Farzaneh Najafi, Talmo D Pereira, Zhenyu Gao, Ilker Ozden, Alexander D Kloth, Eftychios Pnevmatikakis, Liam Paninski, Chris I De Zeeuw, Javier F Medina & Samuel S-H Wang

doi:10.1038/nn.4531

Granule cells constitute half of the cells in the brain, yet their activity during behavior is largely uncharacterized. The authors report that granule cells encode multisensory representations that evolve with learning into a predictive motor signal. This activity may help the cerebellum implement a forward model for action.

See also: News and Views by Becker & Person


Dopamine transients are sufficient and necessary for acquisition of model-based associations pp735 - 742

Melissa J Sharpe, Chun Yun Chang, Melissa A Liu, Hannah M Batchelor, Lauren E Mueller, Joshua L Jones, Yael Niv & Geoffrey Schoenbaum

doi:10.1038/nn.4538

Learning to predict reward is thought to be driven by dopaminergic prediction errors, which reflect discrepancies between actual and expected value. Here the authors show that learning to predict neutral events is also driven by prediction errors and that such value-neutral associative learning is also likely mediated by dopaminergic error signals.


The effect of face patch microstimulation on perception of faces and objects pp743 - 752

Sebastian Moeller, Trinity Crapse, Le Chang & Doris Y Tsao

doi:10.1038/nn.4527

Scientists have long debated the extent to which different brain regions are specialized for specific tasks. Here the authors show that electrical microstimulation of face-selective brain regions in the temporal lobe of monkeys distorts the animal's percept not just of faces but also of certain non-face objects including round objects.

See also: News and Views by Orban


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Technical Report

Differentiation of human and murine induced pluripotent stem cells to microglia-like cells pp753 - 759

Hetal Pandya, Michael J Shen, David M Ichikawa, Andrea B Sedlock, Yong Choi, Kory R Johnson, Gloria Kim, Mason A Brown, Abdel G Elkahloun, Dragan Maric, Colin L Sweeney, Selamawit Gossa, Harry L Malech, Dorian B McGavern & John K Park

doi:10.1038/nn.4534

Pandya et al. describe a protocol to differentiate human and mouse iPSCs into cells with the phenotype, transcriptional profile and functional properties of microglia. The treatment of murine intracranial malignant gliomas with these cells demonstrates their potential clinical use. These microglia-like cells will enable further studies into the role of microglia in health and disease.


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