Neuron: May 16, 2018 (Volume 98, Issue 4)

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[Click here to register.](%2F%2Fwww.workcast.com%2Fregister%3Fcpak=7611522012799566%26referrer=etoc/2/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/7cG_tpfADI9pGPhXonbzCqS9Ggo=57) [Check out the latest jobs in the life sciences on the Cell Career Network](%2F%2Fcareers.cell.com%2F/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/ba4Ua1O9sEV9U-m3xb5voxYBQc4=57) Featured Article --------------------------------------------------------------- [Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30322-2/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/FDV9hbiCr1r7VCSAxyHYKiOsgyQ=57) Gormley et al. Featured Review --------------------------------------------------------------- [The Neural Basis of Timing: Distributed Mechanisms for Diverse Functions](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30251-4/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/cumT4i0CaMm9e5KBvAUnfEzX6Zw=57) Joseph J. Paton, Dean V. Buonomano Online Now --------------------------------------------------------------- [A Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30329-5/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/MvOpsH-pVsnzbZdSRDcsPIxvwJk=57) Stoeber et al. [Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30338-6/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/7aciH1Q8_S_aWD4B7wkYbpRwdUU=57) Teixeira et al. Video Abstract --------------------------------------------------------------- %2F%2Fyoutu.be%2Fd1keam3Wx2U/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/U6tnQdDKiZJpAXenxgB5CCr4-r4=57 [Spectrally Resolved Multi-color Fiber Photometry](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30296-4/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/mS7Yki2L3U-3BISN8qk4XTfPp4Y=57) Using a novel spectrometer-based fiber photometry method, [Meng and colleagues](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30296-4/2/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/5TUTohBNJAiV-OrjM3vivZBJWok=57) show that neural activities are highly synchronized between the striatal direct and indirect pathways and that the magnitude of activation in these two pathways coordinately controls the dynamics and fate of movement. %2F%2Fyoutu.be%2FIxpmGk7P_7k/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/YotYuNB2bTLIJE_hNNHZA_RJoHU=57 [Rapid Astrocyte Calcium Microdomains](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30284-8/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/rMJV_d8-YngcfFA9iFD1fpN1ffM=57) [Scientists from the University of Zurich](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30284-8/2/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/W1_1riB1T6koL3D7ZYIAba63x8U=57) have new evidence that astrocyte calcium signals (“microdomains”) can rapidly follow nearby active neurons. This suggests that astrocytes are fast enough to play a dynamic role in brain circuits. Table of Contents Previews --------------------------------------------------------------- [Common Grounds for Family Maladies](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30378-7%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/pLYnLylxVPi1y9ZQJot-Q9_WMTQ=57) Konrad Oexle, Juliane Winkelmann Rare variants cause Mendelian family aggregation in subsets of common diseases, and common variants may contribute to rare diseases. In this issue of Neuron, Gormley et al. (2018) report that the common variant burden in familial migraine is larger than in migraine of the general population. [Ataxin-2 Is Droppin’ Some Knowledge](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30374-X%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/pg8wx7FGeWK5_7aACKoGrzLrCZM=57) Lindsay A. Becker, Aaron D. Gitler Ataxin-2 is an RNA-binding protein involved in translation regulation and mutated in neurodegenerative diseases, including ALS. In this issue of Neuron, Bakthavachalu et al. (2018) demonstrate that higher order ataxin-2 RNA/protein assemblies are necessary for both translation-dependent learning and ALS-associated neurodegeneration in Drosophila. [Getting “Ras”-ults: Solving Molecular Promiscuity through Microdomain-Selective Targeting](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30373-8%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/cg2Y4xmusEaSfxH4Z95fzOnfDQM=57) Steven A. Connor, Yu Tian Wang In this issue of Neuron, Zhang et al. (2018) report a powerful new method for probing subcellular microdomain-specific signaling in cellular function. Through a microdomain-targeting approach, they delineate how Ras-family GTPases balance signaling diversity with specificity required for various forms of hippocampal synaptic plasticity. [The Map and the Territory: Mapping the Territory Regulated by Serotonergic Signaling at Striatal Projection Neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30372-6%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/hr3Bjs8kMCCB4FY1m0DcHJGNmW0=57) Andrew F. Scheyer, Olivier J. Manzoni In this issue of Neuron, Cavaccini et al. (2018) identify and thoroughly describe a previously unknown role for hyper-localized serotonergic signaling in the modulation of striatal projection neuron plasticity using electrophysiological, chemogenetic, and optogenetic approaches in addition to advanced imaging technology. [It’s About Time: Temporal Dynamics of Dentate Gyrus Pattern Separation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30379-9%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/UCukqSpSFZo14Sqe_FDQjSF5muA=57) Xiaojing Chen, James J. Knierim The dentate gyrus (DG) is hypothesized to be a pattern separator crucial for distinguishing similar memories. In this issue of Neuron, a new study by van Dijk and Fenton (2018) revealed that transient changes of firing patterns of DG ensembles, but not the remapping of session-averaged place fields, contributed to a place discrimination task. Spotlight --------------------------------------------------------------- [Seeing Is Believing: Myelin Dynamics in the Adult CNS](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30377-5%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/1gKwOiZfsniObZpyaxqESt-5lpA=57) Matthew Swire, Charles ffrench-Constant Live imaging studies in mice show that adult-born oligodendrocytes and myelin are remarkably stable. Neural activity enhances oligodendrocyte integration, arguing that internode addition rather than alteration represents the mechanism for any experience-dependent cortical myelination changes that might underpin learning. Review --------------------------------------------------------------- [The Neural Basis of Timing: Distributed Mechanisms for Diverse Functions](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30251-4%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/J4yRbydMG23cZXbUuwf6wUAoZt0=57) Joseph J. Paton, Dean V. Buonomano Temporal processing is among the most fundamental computations the brain performs. Paton and Buonomano review recent experimental and theoretical advances in the field and conclude that timing relies in part on the natural dynamics of neurons and neural circuits. NeuroResource --------------------------------------------------------------- [Spectrally Resolved Fiber Photometry for Multi-component Analysis of Brain Circuits](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30296-4%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/xdfNZ4g188Kclyg-8ZhpPElhJTM=57) Chengbo Meng, Jingheng Zhou, Amy Papaneri, Teja Peddada, Karen Xu, Guohong Cui Using a new method for simultaneous multi-color fluorescence measurements, Meng et al. show that neural activities are synchronized between two parallel striatal pathways, and the magnitude of activation in these two pathways coordinately determines the dynamics and fate of movement. Reports --------------------------------------------------------------- [The GABAA Receptor β Subunit Is Required for Inhibitory Transmission](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30252-6%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/CSbx_mRrpH8nTdWWdbjXRI4aGr0=57) Quynh-Anh Nguyen, Roger A. Nicoll Nguyen and Nicoll use CRISPR/Cas9 to dissect the role of the β subunits in functional GABAA receptors, uncovering synapse-specific requirements governing GABAA receptor subunit composition. [Cortical Circuit Activity Evokes Rapid Astrocyte Calcium Signals on a Similar Timescale to Neurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30284-8%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/ouE_it67H3XYHlhVK_CU6IfgUM4=57) Jillian L. Stobart, Kim David Ferrari, Matthew J.P. Barrett, Chaim Glück, Michael J. Stobart, Marc Zuend, Bruno Weber Stobart et al. have identified fast astrocyte calcium signals that rapidly follow neuronal signals evoked by whisker stimulation in awake mice. These astrocyte signal dynamics are sufficiently fast to influence cortical information processing and/or neurovascular coupling. [Odor Perception on the Two Sides of the Brain: Consistency Despite Randomness](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30288-5%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/YYIGztebzbYQ5DotHOrpuGBqNjQ=57) Evan S. Schaffer, Dan D. Stettler, Daniel Kato, Gloria B. Choi, Richard Axel, L.F. Abbott Random connectivity from the olfactory bulb to piriform implies that the representation of odors will differ in different cortices. Schaffer et al. demonstrate in a model that consistent agreement about odor quality occurs but requires the full complement of piriform neurons. Articles --------------------------------------------------------------- [Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30322-2%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/-ALs-MpakGKSKzgwSrcFIvtmx0A=57) Padhraig Gormley, Mitja I. Kurki, Marjo Eveliina Hiekkala, Kumar Veerapen, Paavo Häppölä, Adele A. Mitchell, Dennis Lal, Priit Palta, Ida Surakka, Mari Anneli Kaunisto, Eija Hämäläinen, Salli Vepsäläinen, Hannele Havanka, Hanna Harno, Matti Ilmavirta, Markku Nissilä, Erkki Säkö, Marja-Liisa Sumelahti, Jarmo Liukkonen, Matti Sillanpää, Liisa Metsähonkala, Seppo Koskinen, Terho Lehtimäki, Olli Raitakari, Minna Männikkö, Caroline Ran, Andrea Carmine Belin, Pekka Jousilahti, Verneri Anttila, Veikko Salomaa, Ville Artto, Markus Färkkilä 23andMe Research Team International Headache Genetics Consortium (IHGC), Heiko Runz, Mark J. Daly, Benjamin M. Neale, Samuli Ripatti, Mikko Kallela, Maija Wessman, Aarno Palotie Gormley et al. use polygenic risk scores to show that common variation, captured by genome-wide association studies, in combination contributes to the aggregation of migraine in families. The results may have similar implications for other complex traits in general. [RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30340-4%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/lhT0VElnKg3KerLrPBZb2Xt9SEY=57) Baskar Bakthavachalu, Joern Huelsmeier, Indulekha P. Sudhakaran, Jens Hillebrand, Amanjot Singh, Arnas Petrauskas, Devasena Thiagarajan, M. Sankaranarayanan, Laura Mizoue, Eric N. Anderson, Udai Bhan Pandey, Eric Ross, K. VijayRaghavan, Roy Parker, Mani Ramaswami Ataxin-2 protein is required for LTM formation and implicated in both ALS and SCA-2. Bakthavachalu et al. show that disordered domains of Ataxin-2 promote mRNP granule assembly as well as long-term memory and cytotoxicity in Drosophila ALS models. [Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30295-2%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/B-4UIGGkloDuPEfk3KhnLeO-eLA=57) Yu-Ting Mao, Julia X. Zhu, Kenji Hanamura, Giuliano Iurilli, Sandeep Robert Datta, Matthew B. Dalva Mao et al. provide a mechanism for local control of synaptic specificity. A transfectable indicator of EphB activity reveals that the decision of filopodia to make synapses or to seek new targets is guided by kinetically distinct signals. [Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30283-6%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/XHWWefjTyswoka6UmaBLwFCAGLY=57) Lei Zhang, Peng Zhang, Guangfu Wang, Huaye Zhang, Yajun Zhang, Yilin Yu, Mingxu Zhang, Jian Xiao, Piero Crespo, Johannes W. Hell, Li Lin, Richard L. Huganir, J. Julius Zhu Zhang et al. develop an effective subcellular microdomain-specific targeted delivery method and demonstrate that homologous proteins (e.g., Ras and Rap) confine their signaling within distinct subcellular microdomains to achieve signal transduction diversity and specificity. [Serotonergic Signaling Controls Input-Specific Synaptic Plasticity at Striatal Circuits](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30292-7%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/ebSzv1eHDRzNP83shFtaIOi2lE8=57) Anna Cavaccini, Marta Gritti, Andrea Giorgi, Andrea Locarno, Nicolas Heck, Sara Migliarini, Alice Bertero, Maddalena Mereu, Giulia Margiani, Massimo Trusel, Tiziano Catelani, Roberto Marotta, Maria Antonietta De Luca, Jocelyne Caboche, Alessandro Gozzi, Massimo Pasqualetti, Raffaella Tonini Cavaccini and Gritti et al. combine chemogenetic and optogenetic approaches to show that serotonergic signaling provides a control mechanism of synaptic plasticity at thalamic inputs to the striatum. [A Brain-wide Circuit Model of Heat-Evoked Swimming Behavior in Larval Zebrafish](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30297-6%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/N-VPmoqGcySOCw9QtDq0WZBRIZE=57) Martin Haesemeyer, Drew N. Robson, Jennifer M. Li, Alexander F. Schier, Florian Engert Haesemeyer et al. combine calcium imaging with behavioral recording and circuit modeling to reveal how temperature information is encoded and transformed in a vertebrate brain to generate behavior using a dynamic modeling strategy suited to capture temporal transformations in activity. [On How the Dentate Gyrus Contributes to Memory Discrimination](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30326-X%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/zmf0gBI0N8MgaqiGRNMtgcQOT1I=57) Milenna Tamara van Dijk, André Antonio Fenton van Dijk and Fenton report that dentate gyrus place cells signal memory discrimination not by remapping, but by variable sub-second patterns of coordinated place cell discharge marked by enhanced discharge coupling between excitatory and inhibitory neurons during memory discrimination. [The Dynamical Regime of Sensory Cortex: Stable Dynamics around a Single Stimulus-Tuned Attractor Account for Patterns of Noise Variability](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30325-8%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/tbvZIsYiVw9d5HdHrFtqti5GjF4=57) Guillaume Hennequin, Yashar Ahmadian, Daniel B. Rubin, Máté Lengyel, Kenneth D. Miller Open Access Stimuli suppress cortical correlated variability. Hennequin et al. show that a cortical operating regime of inhibitory stabilization around a single stable state—the “stabilized supralinear network”—explains this suppression’s tuning and timing, while alternative proposed regimes do not. Corrections --------------------------------------------------------------- [Tau Kinetics in Neurons and the Human Central Nervous System](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30370-2%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/5pea04o9Gi4LyS0d_pTkPOjgI78=57) Chihiro Sato, Nicolas R. Barthélemy, Kwasi G. Mawuenyega, Bruce W. Patterson, Brian A. Gordon, Jennifer Jockel-Balsarotti, Melissa Sullivan, Matthew J. Crisp, Tom Kasten, Kristopher M. Kirmess, Nicholas M. Kanaan, Kevin E. Yarasheski, Alaina Baker-Nigh, Tammie L.S. Benzinger, Timothy M. Miller, Celeste M. Karch, Randall J. Bateman [Avoiding Sibling Conflict: Lessons from Dendrite Self-Avoidance in C. elegans](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30375-1%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/QJPuOiub3cjP-Mu0yEXkvmhiLuA=57) Shelley Halpain [Genetic Dissection of Neural Circuits: A Decade of Progress](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(18)30376-3%3Fdgcid=raven_jbs_etoc_email/1/0100016369b717b3-83918c49-a693-41c7-a133-cb9e30280f43-000000/LxofD4XIVJxM5in2IeSegdgjoTY=57) Liqun Luo, Edward M. 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