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Journal Cover Neuron
  [SJR: 11.464]   [H-I: 372]   [183 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0896-6273 - ISSN (Online) 1097-4199
   Published by Elsevier Homepage  [3089 journals]
  • Fibrinogen in the Nervous System: Glia Beware
    • Authors: Erin H. Norris; Sidney Strickland
      Pages: 951 - 953
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Erin H. Norris, Sidney Strickland
      Re-myelination of CNS nerves after injury is ineffective. Here, Petersen et al. (2017) show that the blood clotting protein fibrinogen inhibits nerve repair by preventing oligodendrocyte progenitor cells from differentiating into myelinating oligodendrocytes. Targeting fibrinogen or its downstream BMP signaling pathway may help with CNS repair.
      Teaser Re-myelination of CNS nerves after injury is ineffective. Here, Petersen et al. (2017) show that the blood clotting protein fibrinogen inhibits nerve repair by preventing oligodendrocyte progenitor cells from differentiating into myelinating oligodendrocytes. Targeting fibrinogen or its downstream BMP signaling pathway may help with CNS repair.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.021
       
  • Seeds of Destruction: New Mechanistic Insights into the Role of
           Apolipoprotein E4 in Alzheimer’s Disease
    • Authors: Robert Vassar
      Pages: 953 - 955
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Robert Vassar
      Apolipoprotein E4 (apoE4) is the strongest genetic risk factor for Alzheimer’s disease. Despite nearly 25 years of research, the mechanism by which apoE4 confers increased risk for Alzheimer’s disease remains enigmatic. In this issue of Neuron, Liu et al. (2017) and Huynh et al. (2017) shed new light on this important question.
      Teaser Apolipoprotein E4 (apoE4) is the strongest genetic risk factor for Alzheimer’s disease. Despite nearly 25 years of research, the mechanism by which apoE4 confers increased risk for Alzheimer’s disease remains enigmatic. In this issue of Neuron, Liu et al. (2017) and Huynh et al. (2017) shed new light on this important question.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.022
       
  • Homeostatic Scaling of AMPA Receptors by Semaphorin
    • Authors: Amy K.Y. Fu; Nancy Y. Ip
      Pages: 955 - 958
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Amy K.Y. Fu, Nancy Y. Ip
      Regulation of AMPA receptors mediates homeostatic scaling. In this issue of Neuron, Wang et al. (2017) identify a new role of secreted semaphorin 3F and elucidate how it triggers synaptic downscaling of AMPA receptors through regulation of the binding of Sema3F holoreceptor complex to AMPA receptors.
      Teaser Regulation of AMPA receptors mediates homeostatic scaling. In this issue of Neuron, Wang et al. (2017) identify a new role of secreted semaphorin 3F and elucidate how it triggers synaptic downscaling of AMPA receptors through regulation of the binding of Sema3F holoreceptor complex to AMPA receptors.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.025
       
  • A Sing-Song Way of Vocalizing: Generalization and Specificity in Language
           and Birdsong
    • Authors: Madza Farias-Virgens; Stephanie A. White
      Pages: 958 - 960
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Madza Farias-Virgens, Stephanie A. White
      Spoken languages such as German are extremely discrete, whereas others such as Portuguese are melodic or “sing-song” wherein identifying a word relies on what comes before and after. Perhaps surprisingly, birdsong also exhibits specificity and generalization as articulated by Tian and Brainard (2017).
      Teaser Spoken languages such as German are extremely discrete, whereas others such as Portuguese are melodic or “sing-song” wherein identifying a word relies on what comes before and after. Perhaps surprisingly, birdsong also exhibits specificity and generalization as articulated by Tian and Brainard.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.027
       
  • John Lisman (1944–2017)
    • Authors: Ole Jensen; Marco Idiart
      Pages: 961 - 963
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Ole Jensen, Marco Idiart


      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.035
       
  • A Commitment to Open Source in Neuroscience
    • Authors: Padraig Gleeson; Andrew P. Davison; R. Angus Silver; Giorgio A. Ascoli
      Pages: 964 - 965
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Padraig Gleeson, Andrew P. Davison, R. Angus Silver, Giorgio A. Ascoli
      Modern neuroscience increasingly relies on custom-developed software, but much of this is not being made available to the wider community. A group of researchers are pledging to make code they produce for data analysis and modeling open source, and are actively encouraging their colleagues to follow suit.
      Teaser Should custom software that is essential to reproducing results of publications be publicly released' Arguing that it must, Gleeson et al. have, together with other researchers, signed a commitment to releasing their code and will ask the same upon peer review.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.10.013
       
  • Pushing the Boundaries of Neuroimaging with Optoacoustics
    • Authors: Saak V. Ovsepian; Ivan Olefir; Gil Westmeyer; Daniel Razansky; Vasilis Ntziachristos
      Pages: 966 - 988
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Saak V. Ovsepian, Ivan Olefir, Gil Westmeyer, Daniel Razansky, Vasilis Ntziachristos
      With the central ability to visualize a variety of endogenous chromophores and biomarkers or exogenous contrast agents, optoacoustic (photoacoustic) imaging empowers new experimental capabilities for investigating brain mechanisms and functions. Here, the operational principles of optoacoustic neuroimaging are reviewed in conjunction with recent advances enabling high-resolution and real-time observation, which extend beyond the reach of optical imaging methods. Multiple implementations of optoacoustics for monitoring hemodynamics and neuro-vascular responses in the brain are showcased. The unique capabilities of optoacoustic imaging for multi-spectral cellular and molecular sensing are discussed with reference to recent application for visualizing healthy and diseased brains. Outstanding challenges in the field are considered in the context of current and future applications of optoacoustic neuroimaging for basic and translational neuroscience research. In pushing the boundaries of brain imaging, optoacoustic methods afford major insights into the neuronal mechanisms of brain functions and organization of behavior.
      Teaser Ovsepian et al. review the state of the art in optoacoustic (photoacoustic) neuroimaging and discuss emerging experimental capabilities and limitations. Multiple implementations at different imaging scales and resolutions are considered in the context of present-day and future studies.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.10.022
       
  • Getting a Handle on Neuropharmacology by Targeting Receptor-Associated
           Proteins
    • Authors: Michael P. Maher; Jose A. Matta; Shenyan Gu; Mark Seierstad; David S. Bredt
      Pages: 989 - 1001
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Michael P. Maher, Jose A. Matta, Shenyan Gu, Mark Seierstad, David S. Bredt
      Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug discovery. Recent studies show that targeting a TARP auxiliary subunit of AMPA receptors selectively modulates neuronal excitability in specific forebrain pathways relevant to epilepsy. Other medicinally important ion channels, gated by glutamate, γ-aminobutyric acid (GABA), and acetylcholine, also have associated proteins, which may be druggable. This emerging pharmacology of receptor-associated proteins provides a new approach for improving drug efficacy while mitigating side effects.
      Teaser Effective treatments for neuropsychiatric disorders require selective modulation of dysfunctional circuits. This review by Maher et al. outlines a strategy for targeting neurotransmitter receptor-associated proteins. This innovative pharmacological approach promises to enhance drug efficacy and minimize side effects.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.10.001
       
  • Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides
           in a Model of β-amyloidosis
    • Authors: Tien-Phat V. Huynh; Fan Liao; Caroline M. Francis; Grace O. Robinson; Javier Remolina Serrano; Hong Jiang; Joseph Roh; Mary Beth Finn; Patrick M. Sullivan; Thomas J. Esparza; Floy R. Stewart; Thomas E. Mahan; Jason D. Ulrich; Tracy Cole; David M. Holtzman
      Pages: 1013 - 1023.e4
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Tien-Phat V. Huynh, Fan Liao, Caroline M. Francis, Grace O. Robinson, Javier Remolina Serrano, Hong Jiang, Joseph Roh, Mary Beth Finn, Patrick M. Sullivan, Thomas J. Esparza, Floy R. Stewart, Thomas E. Mahan, Jason D. Ulrich, Tracy Cole, David M. Holtzman
      The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease. Previous studies suggest that reduction of apoE levels through genetic manipulation can reduce Aβ pathology. However, it is not clear how reduction of apoE levels after birth would affect amyloid deposition. We utilize an antisense oligonucleotide (ASO) to reduce apoE expression in the brains of APP/PS1-21 mice homozygous for the APOE-ε4 or APOE-ε3 allele. ASO treatment starting after birth led to a significant decrease in Aβ pathology when assessed at 4 months. Interestingly, ASO treatment starting at the onset of amyloid deposition led to an increase in Aβ plaque size and a reduction in plaque-associated neuritic dystrophy with no change in overall plaque load. These results suggest that lowering apoE levels prior to plaque deposition can strongly affect the initiation of Aβ pathology while lowering apoE after Aβ seeding modulates plaque size and toxicity.
      Teaser Huynh et al. demonstrated that apoE3 and apoE4 are critical factors in promoting amyloidosis during the early stages of Aβ plaque formation but not during the exponential growth phase. Importantly, reduction of apoE4 decreases neuritic dystrophy independent of Aβ pathology.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.014
       
  • ApoE4 Accelerates Early Seeding of Amyloid Pathology
    • Authors: Chia-Chen Liu; Na Zhao; Yuan Fu; Na Wang; Cynthia Linares; Chih-Wei Tsai; Guojun Bu
      Pages: 1024 - 1032.e3
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Chia-Chen Liu, Na Zhao, Yuan Fu, Na Wang, Cynthia Linares, Chih-Wei Tsai, Guojun Bu
      Accumulation and aggregation of amyloid-β (Aβ) in the brain is an initiating step in the pathogenesis of Alzheimer’s disease (AD). The ε4 allele of apolipoprotein E (apoE) gene is the strongest genetic risk factor for late-onset AD. Although there is strong evidence showing that apoE4 enhances amyloid pathology, it is not clear what the critical stage(s) is during amyloid development in which apoE4 has the strongest impact. Using apoE inducible mouse models, we show that increased expression of astrocytic apoE4, but not apoE3, during the seeding stage of amyloid development enhanced amyloid deposition and neuritic dystrophy in amyloid model mice. ApoE4, but not apoE3, significantly increased brain Aβ half-life measured by in vivo microdialysis. Furthermore, apoE4 expression increased whereas apoE3 reduced amyloid-related gliosis in the mouse brains. Together, our results demonstrate that apoE4 has the greatest impact on amyloid during the seeding stage, likely by perturbing Aβ clearance and enhancing Aβ aggregation.
      Teaser Liu et al. have developed cell-type-specific and inducible apoE mouse models and demonstrate that astrocytic apoE4 is a potent factor in promoting amyloidosis during the seeding stage, but not the rapid growth period, of amyloid development. ApoE4 impairs Aβ clearance and accelerates Aβ aggregation, leading to enhanced amyloid pathology and neuritic dystrophy.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.013
       
  • Endocannabinoid Actions on Cortical Terminals Orchestrate Local Modulation
           of Dopamine Release in the Nucleus Accumbens
    • Authors: Yolanda Mateo; Kari A. Johnson; Dan P. Covey; Brady K. Atwood; Hui-Ling Wang; Shiliang Zhang; Iness Gildish; Roger Cachope; Luigi Bellocchio; Manuel Guzmán; Marisela Morales; Joseph F. Cheer; David M. Lovinger
      Pages: 1112 - 1126.e5
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Yolanda Mateo, Kari A. Johnson, Dan P. Covey, Brady K. Atwood, Hui-Ling Wang, Shiliang Zhang, Iness Gildish, Roger Cachope, Luigi Bellocchio, Manuel Guzmán, Marisela Morales, Joseph F. Cheer, David M. Lovinger
      Dopamine (DA) transmission mediates numerous aspects of behavior. Although DA release is strongly linked to firing of DA neurons, recent developments indicate the importance of presynaptic modulation at striatal dopaminergic terminals. The endocannabinoid (eCB) system regulates DA release and is a canonical gatekeeper of goal-directed behavior. Here we report that extracellular DA increases induced by selective optogenetic activation of cholinergic neurons in the nucleus accumbens (NAc) are inhibited by CB1 agonists and eCBs. This modulation requires CB1 receptors on cortical glutamatergic afferents. Dopamine increases driven by optogenetic activation of prefrontal cortex (PFC) terminals in the NAc are similarly modulated by activation of these CB1 receptors. We further demonstrate that this same population of CB1 receptors modulates optical self-stimulation sustained by activation of PFC afferents in the NAc. These results establish local eCB actions on PFC terminals within the NAc that inhibit mesolimbic DA release and constrain reward-driven behavior.
      Teaser Mateo et al. demonstrate that glutamate and acetylcholine-driven dopamine release in the nucleus accumbens is modulated by CB1 receptors on prefrontal cortical afferents. Endogenous activation of these receptors modifies dopamine-dependent reward-driven behavior sustained by optical activation of prefrontal cortical terminals.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.012
       
  • Mechanosensory-Based Phase Coding of Odor Identity in the Olfactory Bulb
    • Authors: Ryo Iwata; Hiroshi Kiyonari; Takeshi Imai
      Pages: 1139 - 1152.e7
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Ryo Iwata, Hiroshi Kiyonari, Takeshi Imai
      Mitral and tufted (M/T) cells in the olfactory bulb produce rich temporal patterns of activity in response to different odors. However, it remains unknown how these temporal patterns are generated and how they are utilized in olfaction. Here we show that temporal patterning effectively discriminates between the two sensory modalities detected by olfactory sensory neurons (OSNs): odor and airflow-driven mechanical signals. Sniff-induced mechanosensation generates glomerulus-specific oscillatory activity in M/T cells, whose phase was invariant across airflow speed. In contrast, odor stimulation caused phase shifts (phase coding). We also found that odor-evoked phase shifts are concentration invariant and stable across multiple sniff cycles, contrary to the labile nature of rate coding. The loss of oscillatory mechanosensation impaired the precision and stability of phase coding, demonstrating its role in olfaction. We propose that phase, not rate, coding is a robust encoding strategy of odor identity and is ensured by airflow-induced mechanosensation in OSNs.
      Teaser Iwata et al. demonstrate that phase coding, but not rate coding, in mitral cells is useful for concentration-invariant odor identity coding. They also found that mechanosensation in olfactory sensory neurons facilitates, rather than masks, the robust phase coding of odors.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.008
       
  • A Sensorimotor Circuit in Mouse Cortex for Visual Flow Predictions
    • Authors: Marcus Leinweber; Daniel R. Ward; Jan M. Sobczak; Alexander Attinger; Georg B. Keller
      First page: 1204
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Marcus Leinweber, Daniel R. Ward, Jan M. Sobczak, Alexander Attinger, Georg B. Keller


      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.009
       
  • DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of
           Ndel1/Nde1 during Mitosis
    • Authors: Fei Ye; Eunchai Kang; Chuan Yu; Xuyu Qian; Fadi Jacob; Cong Yu; Mao Mao; Randy Y.C. Poon; Jieun Kim; Hongjun Song; Guo-li Ming; Mingjie Zhang
      First page: 1204
      Abstract: Publication date: 6 December 2017
      Source:Neuron, Volume 96, Issue 5
      Author(s): Fei Ye, Eunchai Kang, Chuan Yu, Xuyu Qian, Fadi Jacob, Cong Yu, Mao Mao, Randy Y.C. Poon, Jieun Kim, Hongjun Song, Guo-li Ming, Mingjie Zhang


      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.034
       
  • GABAergic Synaptogenesis: A Case for Cooperation
    • Authors: Jean-Marc Fritschy; Shiva K. Tyagarajan
      Pages: 709 - 711
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Jean-Marc Fritschy, Shiva K. Tyagarajan
      Multiple cell-adhesion molecules contribute to synapse formation by mediating trans-synaptic interactions with presynaptic signaling molecules. In this issue of Neuron, Li et al. (2017) report cooperativity between Neuroligin2 and Slitrk3, exerting distinct effects on GABAergic synapse formation in immature and mature neurons.
      Teaser Multiple cell-adhesion molecules contribute to synapse formation by mediating trans-synaptic interactions with presynaptic signaling molecules. In this issue of Neuron, Li et al. (2017) report cooperativity between Neuroligin2 and Slitrk3, exerting distinct effects on GABAergic synapse formation in immature and mature neurons.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.11.003
       
  • A Synaptic Basis for GLP-1 Action in the Brain
    • Authors: Sandrine Lefort; Matthias H. Tschöp; Cristina García-Cáceres
      Pages: 713 - 715
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Sandrine Lefort, Matthias H. Tschöp, Cristina García-Cáceres
      Unraveling the brain control of metabolism may generate opportunities to discover novel precision medicines for obesity and diabetes. In this issue of Neuron, Liu et al. (2017) identify a novel glucagon-like peptide (GLP)-1 receptor-dependent signaling process that exerts anorexigenic action via the regulation of AMPA receptor subunit composition in the hypothalamus.
      Teaser Unraveling the brain control of metabolism may generate opportunities to discover novel precision medicines for obesity and diabetes. In this issue of Neuron, Liu et al. identify a novel glucagon-like peptide (GLP)-1 receptor-dependent signaling process that exerts anorexigenic action via the regulation of AMPA receptor subunit composition in the hypothalamus.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.034
       
  • Good Vibrations: Resting-State Functional Connectivity Reflects
           Entrainment of Vasomotion
    • Authors: Allen W. Chan; Timothy H. Murphy
      Pages: 716 - 717
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Allen W. Chan, Timothy H. Murphy
      In this issue of Neuron, Mateo et al. (2017) suggest that hemodynamic measures of resting-state functional connectivity in cortex are reporting the consequences of entrainment of arteriole vasomotion by neuronal activity.
      Teaser In this issue of Neuron, Mateo et al. (2017) suggest that hemodynamic measures of resting-state functional connectivity in cortex are reporting the consequences of entrainment of arteriole vasomotion by neuronal activity.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.035
       
  • Epimetronomics: m6A Marks the Tempo of Corticogenesis
    • Authors: Nathan C. Boles; Sally Temple
      Pages: 718 - 720
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Nathan C. Boles, Sally Temple
      Yoon et al. (2017) uncover a key role for the m6A RNA mark in regulating the timing of cerebral cortex development in mouse and human. This discovery opens new avenues of exploration into how the epitranscriptome helps orchestrate central nervous system formation.
      Teaser Yoon et al. (2017) uncover a key role for the m6A RNA mark in regulating the timing of cerebral cortex development in mouse and human. This discovery opens new avenues of exploration into how the epitranscriptome helps orchestrate central nervous system formation.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.11.002
       
  • Gender Equality from a European Perspective: Myth and Reality
    • Authors: Patricia C. Salinas; Claudia Bagni
      Pages: 721 - 729
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Patricia C. Salinas, Claudia Bagni
      In the past 50 years, significant progress in women’s equality has been made worldwide. Western countries, particularly European countries, have implemented initiatives to attain a more gender-balanced workforce with the introduction of family friendly policies, by trying to narrow the gender pay gap and by promoting women’s career progression. In academia, however, fewer women reach top leadership positions than those in the political arena. These findings suggest that academia needs to carefully evaluate why these new policies have not been very effective. In this NeuroView, we report on the progress made in higher education, the shortcomings, and how new initiatives hold great promise for improving gender equality in academia around the globe.
      Teaser Salinas and Bagni discuss the state of gender equality in higher education in Europe. Despite significant progress, women still face many challenges to achieve equal opportunity in academia.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.002
       
  • Building Bridges through Science
    • Authors: Thomas Lissek; Michelle Adams; John Adelman; Ehud Ahissar; Mohammed Akaaboune; Huda Akil; Mustafa al’Absi; Fazal Arain; Juan Carlos Arango-Lasprilla; Deniz Atasoy; Jesus Avila; Ashraf Badawi; Hilmar Bading; Abdul Mannan Baig; Jimena Baleriola; Carlos Belmonte; Ilaria Bertocchi; Heinrich Betz; Colin Blakemore; Olaf Blanke; Philipp Boehm-Sturm; Tobias Bonhoeffer; Paolo Bonifazi; Nils Brose; Patrizia Campolongo; Tansu Celikel; Cathy C. Chang; Ta-Yuan Chang; Ami Citri; Hollis T. Cline; Jesus M. Cortes; Kathleen Cullen; Kellie Dean; José M. Delgado-Garcia; Mathieu Desroches; John F. Disterhoft; John E. Dowling; Andreas Draguhn; Sherif F. El-Khamisy; Abdeljabbar El Manira; S. Ather Enam; Juan M. Encinas; Asier Erramuzpe; José A. Esteban; Isabel Fariñas; Edmond Fischer; Izumi Fukunaga; Iñigo Gabilondo; Detlev Ganten; Albert Gidon; Juan Carlos Gomez-Esteban; Paul Greengard; Valery Grinevich; Agnés Gruart; Roger Guillemin; Ahmad R. Hariri; Bassem Hassan; Michael Häusser; Yasunori Hayashi; Natasha K. Hussain; Adnan Abdul Jabbar; Mohamed Jaber; Reinhardt Jahn; Essam Mohammed Janahi; Mohamed Kabbaj; Helmut Kettenmann; Merel Kindt; Shira Knafo; Georg Köhr; Shoji Komai; Harm Krugers; Bernd Kuhn; Nouria Lakhdar Ghazal; Matthew E. Larkum; Mickey London; Beat Lutz; Carlos Matute; Luis Martinez-Millan; Mouna Maroun; James McGaugh; Ahmed A. Moustafa; Anwar Nasim; Klaus-Armin Nave; Erwin Neher; Karoly Nikolich; Tiago Outeiro; Lucy M. Palmer; Olga Penagarikano; Isabel Perez-Otano; Donald W. Pfaff; Bruno Poucet; Atta-ur Rahman; Pedro Ramos-Cabrer; Ali Rashidy-Pour; Richard J. Roberts; Serafim Rodrigues; Joshua R. Sanes; Andreas T. Schaefer; Menahem Segal; Idan Segev; Saad Shafqat; Nikhat Ahmed Siddiqui; Hermona Soreq; Eduardo Soriano-García; Rainer Spanagel; Rolf Sprengel; Greg Stuart; Thomas C. Südhof; Jan Tønnesen; Mario Treviño; Basim M. Uthman; J. Craig Venter; Alexei Verkhratsky; Craig Weiss; Torsten N. Wiesel; Emre Yaksi; Ofer Yizhar; Larry J. Young; Paul Young; Nasser H. Zawia; José L. Zugaza; Mazahir T. Hasan
      Pages: 730 - 735
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Thomas Lissek, Michelle Adams, John Adelman, Ehud Ahissar, Mohammed Akaaboune, Huda Akil, Mustafa al’Absi, Fazal Arain, Juan Carlos Arango-Lasprilla, Deniz Atasoy, Jesus Avila, Ashraf Badawi, Hilmar Bading, Abdul Mannan Baig, Jimena Baleriola, Carlos Belmonte, Ilaria Bertocchi, Heinrich Betz, Colin Blakemore, Olaf Blanke, Philipp Boehm-Sturm, Tobias Bonhoeffer, Paolo Bonifazi, Nils Brose, Patrizia Campolongo, Tansu Celikel, Cathy C. Chang, Ta-Yuan Chang, Ami Citri, Hollis T. Cline, Jesus M. Cortes, Kathleen Cullen, Kellie Dean, José M. Delgado-Garcia, Mathieu Desroches, John F. Disterhoft, John E. Dowling, Andreas Draguhn, Sherif F. El-Khamisy, Abdeljabbar El Manira, S. Ather Enam, Juan M. Encinas, Asier Erramuzpe, José A. Esteban, Isabel Fariñas, Edmond Fischer, Izumi Fukunaga, Iñigo Gabilondo, Detlev Ganten, Albert Gidon, Juan Carlos Gomez-Esteban, Paul Greengard, Valery Grinevich, Agnés Gruart, Roger Guillemin, Ahmad R. Hariri, Bassem Hassan, Michael Häusser, Yasunori Hayashi, Natasha K. Hussain, Adnan Abdul Jabbar, Mohamed Jaber, Reinhardt Jahn, Essam Mohammed Janahi, Mohamed Kabbaj, Helmut Kettenmann, Merel Kindt, Shira Knafo, Georg Köhr, Shoji Komai, Harm Krugers, Bernd Kuhn, Nouria Lakhdar Ghazal, Matthew E. Larkum, Mickey London, Beat Lutz, Carlos Matute, Luis Martinez-Millan, Mouna Maroun, James McGaugh, Ahmed A. Moustafa, Anwar Nasim, Klaus-Armin Nave, Erwin Neher, Karoly Nikolich, Tiago Outeiro, Lucy M. Palmer, Olga Penagarikano, Isabel Perez-Otano, Donald W. Pfaff, Bruno Poucet, Atta-ur Rahman, Pedro Ramos-Cabrer, Ali Rashidy-Pour, Richard J. Roberts, Serafim Rodrigues, Joshua R. Sanes, Andreas T. Schaefer, Menahem Segal, Idan Segev, Saad Shafqat, Nikhat Ahmed Siddiqui, Hermona Soreq, Eduardo Soriano-García, Rainer Spanagel, Rolf Sprengel, Greg Stuart, Thomas C. Südhof, Jan Tønnesen, Mario Treviño, Basim M. Uthman, J. Craig Venter, Alexei Verkhratsky, Craig Weiss, Torsten N. Wiesel, Emre Yaksi, Ofer Yizhar, Larry J. Young, Paul Young, Nasser H. Zawia, José L. Zugaza, Mazahir T. Hasan
      Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched “The Science Bridge” initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.
      Teaser Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, Lissek et al. have launched “The Science Bridge” initiative. Theirs current project focuses on partnership between Western and Middle Eastern neuroscience communities.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.09.028
       
  • Orbitofrontal Cortex: A Neural Circuit for Economic Decisions
    • Authors: Camillo Padoa-Schioppa; Katherine E. Conen
      Pages: 736 - 754
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Camillo Padoa-Schioppa, Katherine E. Conen
      Economic choice behavior entails the computation and comparison of subjective values. A central contribution of neuroeconomics has been to show that subjective values are represented explicitly at the neuronal level. With this result at hand, the field has increasingly focused on the difficult question of where in the brain and how exactly subjective values are compared to make a decision. Here, we review a broad range of experimental and theoretical results suggesting that good-based decisions are generated in a neural circuit within the orbitofrontal cortex (OFC). The main lines of evidence supporting this proposal include the fact that goal-directed behavior is specifically disrupted by OFC lesions, the fact that different groups of neurons in this area encode the input and the output of the decision process, the fact that activity fluctuations in each of these cell groups correlate with choice variability, and the fact that these groups of neurons are computationally sufficient to generate decisions. Results from other brain regions are consistent with the idea that good-based decisions take place in OFC and indicate that value signals inform a variety of mental functions. We also contrast the present proposal with other leading models for the neural mechanisms of economic decisions. Finally, we indicate open questions and suggest possible directions for future research.
      Teaser Padoa-Schioppa and Conen review recent advances on the neuronal mechanisms underlying economic choices. They propose that good-based decisions are formed in a neural circuit within the orbitofrontal cortex.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.09.031
       
  • Virus-Mediated Genome Editing via Homology-Directed Repair in Mitotic and
           Postmitotic Cells in Mammalian Brain
    • Authors: Jun Nishiyama; Takayasu Mikuni; Ryohei Yasuda
      Pages: 755 - 768.e5
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Jun Nishiyama, Takayasu Mikuni, Ryohei Yasuda
      Precise genome editing via homology-directed repair (HDR) in targeted cells, particularly in vivo, provides an invaluable tool for biomedical research. However, HDR has been considered to be largely restricted to dividing cells, making it challenging to apply the technique in postmitotic neurons. Here we show that precise genome editing via HDR is possible in mature postmitotic neurons as well as mitotic cells in mice brain by combining CRISPR-Cas9-mediated DNA cleavage and the efficient delivery of donor template with adeno-associated virus (AAV). Using this strategy, we achieved efficient tagging of endogenous proteins in primary and organotypic cultures in vitro and developing, adult, aged, and pathological brains in vivo. Thus, AAV- and CRISPR-Cas9-mediated HDR will be broadly useful for precise genome editing in basic and translational neuroscience.
      Teaser Nishiyama et al. show that precise genome editing via HDR is possible in mature postmitotic neurons as well as mitotic cells in the mammalian brain by combining CRISPR-Cas9-mediated DNA cleavage and the efficient delivery of donor template with AAV.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.004
       
  • A Large-Scale Semi-Chronic Microdrive Recording System for Non-Human
           Primates
    • Authors: Nicholas M. Dotson; Steven J. Hoffman; Baldwin Goodell; Charles M. Gray
      Pages: 769 - 782.e2
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Nicholas M. Dotson, Steven J. Hoffman, Baldwin Goodell, Charles M. Gray
      Multi-electrode recordings in the non-human primate provide a critical method for measuring the widely distributed activity patterns that underlie brain function. However, common techniques rely on small, often immovable arrays, or microdrives, that are only capable of manipulating a small number of closely spaced probes. These techniques restrict the number of cortical areas that can be simultaneously sampled and are typically not capable of reaching subcortical targets. To overcome these limitations, we developed a large-scale, semi-chronic microdrive recording system with up to 256 independently movable microelectrodes spanning an entire cerebral hemisphere. The microdrive system is hermetically sealed, free of internal connecting wires, and has been used to simultaneously record from up to 37 cortical and subcortical areas in awake behaving monkeys for up to 9 months. As a proof of principle, we demonstrate the capability of this technique to address network-level questions using a graph theoretic analysis of functional connectivity data.
      Teaser Dotson et al. developed and implemented a large-scale, semi-chronic microdrive recording system for non-human primates. Devices remained on the monkeys for up to 9 months, and they were able to make simultaneous recordings from up to 37 cortical and subcortical areas.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.09.050
       
  • Transsynaptic Mapping of Second-Order Taste Neurons in Flies by
           trans-Tango
    • Authors: Mustafa Talay; Ethan B. Richman; Nathaniel J. Snell; Griffin G. Hartmann; John D. Fisher; Altar Sorkaç; Juan F. Santoyo; Cambria Chou-Freed; Nived Nair; Mark Johnson; John R. Szymanski; Gilad Barnea
      Pages: 783 - 795.e4
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Mustafa Talay, Ethan B. Richman, Nathaniel J. Snell, Griffin G. Hartmann, John D. Fisher, Altar Sorkaç, Juan F. Santoyo, Cambria Chou-Freed, Nived Nair, Mark Johnson, John R. Szymanski, Gilad Barnea
      Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describe trans-Tango, a technique for anterograde transsynaptic circuit tracing and manipulation. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners and providing genetic access to these neurons. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the first-order receptor neurons are not fully characterized. We identified putative second-order neurons within the sweet circuit that include projection neurons targeting known neuromodulation centers in the brain. These experiments establish trans-Tango as a flexible platform for transsynaptic circuit analysis.
      Teaser Talay and Richman et al. develop a genetic method for transsynaptic labeling of neural circuits in Drosophila. They validate it in the olfactory system and implement it in the gustatory system to reveal second-order projections of sweet tastant-responsive neurons.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.011
       
  • Age-Dependent Dopaminergic Neurodegeneration and Impairment of the
           Autophagy-Lysosomal Pathway in LRRK-Deficient Mice
    • Authors: Emilie Giaime; Youren Tong; Lisa K. Wagner; Yang Yuan; Guodong Huang; Jie Shen
      Pages: 796 - 807.e6
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Emilie Giaime, Youren Tong, Lisa K. Wagner, Yang Yuan, Guodong Huang, Jie Shen
      LRRK2 mutations are the most common genetic cause of Parkinson’s disease, but LRRK2’s normal physiological role in the brain is unclear. Here, we show that inactivation of LRRK2 and its functional homolog LRRK1 results in earlier mortality and age-dependent, selective neurodegeneration. Loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and of noradrenergic neurons in the locus coeruleus is accompanied with increases in apoptosis, whereas the cerebral cortex and cerebellum are unaffected. Furthermore, selective age-dependent neurodegeneration is only present in LRRK −/−, not LRRK1 −/− or LRRK2 −/− brains, and it is accompanied by increases in α-synuclein and impairment of the autophagy-lysosomal pathway. Quantitative electron microscopy (EM) analysis revealed age-dependent increases of autophagic vacuoles in the SNpc of LRRK −/− mice before the onset of DA neuron loss. These findings revealed an essential role of LRRK in the survival of DA neurons and in the regulation of the autophagy-lysosomal pathway in the aging brain.
      Teaser Mutations in the LRRK2 gene are the most common genetic cause of Parkinson’s disease. Giaime et al. show an essential role of LRRK in the survival of dopaminergic neurons and the regulation of the autophagy-lysosomal pathway in the aging brain.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.09.036
       
  • RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to
           Secure a Fluid Walking Gait
    • Authors: Stephanie C. Koch; Marta Garcia Del Barrio; Antoine Dalet; Graziana Gatto; Thomas Günther; Jingming Zhang; Barbara Seidler; Dieter Saur; Roland Schüle; Martyn Goulding
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Stephanie C. Koch, Marta Garcia Del Barrio, Antoine Dalet, Graziana Gatto, Thomas Günther, Jingming Zhang, Barbara Seidler, Dieter Saur, Roland Schüle, Martyn Goulding
      Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORβ orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory RORβ IN function result in an ataxic gait characterized by exaggerated flexion movements and marked alterations to the step cycle. Inactivation of RORβ in inhibitory neurons leads to reduced presynaptic inhibition and changes to sensory-evoked reflexes, arguing that the RORβ inhibitory INs function to suppress the sensory transmission pathways that activate flexor motor reflexes and interfere with the ongoing locomotor program.
      Teaser Koch et al. identify an inhibitory spinal circuit that is required for fluid rhythmic stepping movements. Inhibitory RORβ+ neurons in the spinal cord selectively gate proprioceptive transmission during locomotion by a presynaptic mechanism.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.011
       
  • Neural Basis of Cognitive Control over Movement Inhibition: Human fMRI and
           Primate Electrophysiology Evidence
    • Authors: Kitty Z. Xu; Brian A. Anderson; Erik E. Emeric; Anthony W. Sali; Veit Stuphorn; Steven Yantis; Susan M. Courtney
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Kitty Z. Xu, Brian A. Anderson, Erik E. Emeric, Anthony W. Sali, Veit Stuphorn, Steven Yantis, Susan M. Courtney
      Executive control involves the ability to flexibly inhibit or change an action when it is contextually inappropriate. Using the complimentary techniques of human fMRI and monkey electrophysiology in a context-dependent stop signal task, we found a functional double dissociation between the right ventrolateral prefrontal cortex (rVLPFC) and the bi-lateral frontal eye field (FEF). Different regions of rVLPFC were associated with context-based signal meaning versus intention to inhibit a response, while FEF activity corresponded to success or failure of the response inhibition regardless of the stimulus response mapping or the context. These results were validated by electrophysiological recordings in rVLPFC and FEF from one monkey. Inhibition of a planned behavior is therefore likely not governed by a single brain system as had been previously proposed, but instead depends on two distinct neural processes involving different sub-regions of the rVLPFC and their interactions with other motor-related brain regions.
      Teaser Xu et al. present a rare combination of complementary evidence from human fMRI and primate neurophysiology, demonstrating that response inhibition is not directly accomplished by the rVLPFC, but instead requires multiple, distinct rVLPFC networks involving attention and contextual stimulus interpretation.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.010
       
  • NRAP-1 Is a Presynaptically Released NMDA Receptor Auxiliary Protein that
           Modifies Synaptic Strength
    • Authors: Ning Lei; Jerry E. Mellem; Penelope J. Brockie; David M. Madsen; Andres V. Maricq
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Ning Lei, Jerry E. Mellem, Penelope J. Brockie, David M. Madsen, Andres V. Maricq
      NMDA receptors (NMDARs) are a subtype of postsynaptic ionotropic glutamate receptors that function as molecular coincidence detectors, have critical roles in models of learning, and are associated with a variety of neurological and psychiatric disorders. To date, no auxiliary proteins that modify NMDARs have been identified. Here, we report the identification of NRAP-1, an auxiliary protein in C. elegans that modulates NMDAR function. NMDAR-mediated currents were eliminated in nrap-1 mutants, as was NMDA-dependent behavior. We show that reconstitution of NMDA-gated current in Xenopus oocytes, or C. elegans muscle cells, depends on NRAP-1 and that recombinant NRAP-1 can convert silent NMDARs to functional channels. Our data indicate that NRAP-1, secreted from presynaptic neurons, localizes to glutamatergic synapses, where it associates with postsynaptic NMDARs to modify receptor gating. Thus, our studies reveal a novel mechanism for synaptic regulation via pre-synaptic control of NMDAR-mediated synaptic transmission.
      Teaser Lei et al. have discovered NRAP-1, the first identified NMDAR auxiliary protein. NRAP-1, secreted from presynaptic neurons, modulates the properties of postsynaptic NMDARs. Trans-synaptic modulation of receptor function by NRAP-1 reveals a novel mechanism used to regulate synaptic strength.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.019
       
  • Synergistic Processing of Visual Contours across Cortical Layers in V1 and
           V2
    • Authors: Rujia Chen; Feng Wang; Hualou Liang; Wu Li
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Rujia Chen, Feng Wang, Hualou Liang, Wu Li
      Visual cortical areas are interconnected via layer-specific feedforward and feedback projections. Such intricate connections are thought to be essential for parsing complex visual images, but the synergy among different layers in different cortical areas remains unclear. By simultaneously mapping neuronal activities across cortical depths in V1 and V2 of behaving monkeys, we identified spatiotemporally dissociable processes for grouping contour fragments and segregating background components. These processes generated and amplified contour signals within specific layers in V1 and V2. Contour-related inter-areal interactions, measured as Granger causality, were also dominant between these cortical layers within a time window when the contour signals were rapidly augmented. The grouping process became much faster for isolated contour elements compared with visual contours embedded in a complex background. Our results delineate the mode whereby image components are grouped and segmented through synergistic inter-laminar and inter-areal processes that are dynamically adjusted during interpretation of sensory inputs.
      Teaser By simultaneously mapping neuronal activities across cortical layers in monkey V1 and V2, Chen et al. show how image components are grouped and segregated through inter-areal and inter-laminar interactions, highlighting the dynamics and complexity of multilayered information processing.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.004
       
  • Injecting Instructions into Premotor Cortex
    • Authors: Kevin A. Mazurek; Marc H. Schieber
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Kevin A. Mazurek, Marc H. Schieber
      The premotor cortex (PM) receives inputs from parietal cortical areas representing processed visuospatial information, translates that information into programs for particular movements, and communicates those programs to the primary motor cortex (M1) for execution. Consistent with this general function, intracortical microstimulation (ICMS) in the PM of sufficient frequency, amplitude, and duration has been shown to evoke complex movements of the arm and hand that vary systematically depending on the locus of stimulation. Using frequencies and amplitudes too low to evoke muscle activity, however, we found that ICMS in the PM can provide instructions to perform specific reach, grasp, and manipulate movements. These instructed actions were not fixed but rather were learned through associations between the arbitrary stimulation locations and particular movements. Low-amplitude ICMS at different PM locations thus evokes distinguishable experiences that can become associated with specific movements arbitrarily, providing a novel means of injecting information into the nervous system.
      Teaser The premotor cortex is thought to translate visuospatial information into plans for particular movements. In this issue of Neuron, Mazurek and Schieber demonstrate that specific movements can be instructed with low-amplitude microstimulation delivered at arbitrary premotor cortex locations.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.006
       
  • Social Media, Open Science, and Data Science Are Inextricably Linked
    • Authors: Bradley Voytek
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Bradley Voytek
      Should scientists use social media' Why practice open science' What is data science' Ten years ago, these phrases hardly existed. Now they are ubiquitous. Here I argue that these phenomena are inextricably linked and reflect similar underlying social and technological transformations.
      Teaser In this NeuroView, Voytek argues that several major social and technological shifts—social media, open science, and data science—are not independent, but rather are inextricably linked. Additionally, Voytek outlines how these phenomena are influencing modern scientific practice and communication.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.015
       
  • Decoding a Decision Process in the Neuronal Population of Dorsal Premotor
           Cortex
    • Authors: Román Rossi-Pool; Antonio Zainos; Manuel Alvarez; Jerónimo Zizumbo; José Vergara; Ranulfo Romo
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Román Rossi-Pool, Antonio Zainos, Manuel Alvarez, Jerónimo Zizumbo, José Vergara, Ranulfo Romo
      When trained monkeys discriminate the temporal structure of two sequential vibrotactile stimuli, dorsal premotor cortex (DPC) showed high heterogeneity among its neuronal responses. Notably, DPC neurons coded stimulus patterns as broader categories and signaled them during working memory, comparison, and postponed decision periods. Here, we show that such population activity can be condensed into two major coding components: one that persistently represented in working memory both the first stimulus identity and the postponed informed choice and another that transiently coded the initial sensory information and the result of the comparison between the two stimuli. Additionally, we identified relevant signals that coded the timing of task events. These temporal and task-parameter readouts were shown to be strongly linked to the monkeys’ behavior when contrasted to those obtained in a non-demanding cognitive control task and during error trials. These signals, hidden in the heterogeneity, were prominently represented by the DPC population response.
      Teaser Rossi-Pool et al. show that the population response of dorsal premotor cortex codes information about event timing, parameters, and decision outcome of a temporal pattern discrimination task. The authors provide evidence that this population code co-varies with behavior.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.023
       
  • High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and
           Connectivity of Cortical Input and Output in Human M1
    • Authors: Laurentius Huber; Daniel A. Handwerker; David C. Jangraw; Gang Chen; Andrew Hall; Carsten Stüber; Javier Gonzalez-Castillo; Dimo Ivanov; Sean Marrett; Maria Guidi; Jozien Goense; Benedikt A. Poser; Peter A. Bandettini
      Abstract: Publication date: Available online 7 December 2017
      Source:Neuron
      Author(s): Laurentius Huber, Daniel A. Handwerker, David C. Jangraw, Gang Chen, Andrew Hall, Carsten Stüber, Javier Gonzalez-Castillo, Dimo Ivanov, Sean Marrett, Maria Guidi, Jozien Goense, Benedikt A. Poser, Peter A. Bandettini
      Layer-dependent fMRI allows measurements of information flow in cortical circuits, as afferent and efferent connections terminate in different cortical layers. However, it is unknown to what level human fMRI is specific and sensitive enough to reveal directional functional activity across layers. To answer this question, we developed acquisition and analysis methods for blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used these to discriminate four different tasks in the human motor cortex (M1). In agreement with anatomical data from animal studies, we found evidence for somatosensory and premotor input in superficial layers of M1 and for cortico-spinal motor output in deep layers. Laminar resting-state fMRI showed directional functional connectivity of M1 with somatosensory and premotor areas. Our findings demonstrate that CBV-fMRI can be used to investigate cortical activity in humans with unprecedented detail, allowing investigations of information flow between brain regions and outperforming conventional BOLD results that are often buried under vascular biases.
      Teaser Huber et al. demonstrate an MRI method to measure brain activity changes at the spatial resolution of cortical layers in humans. This allows investigations of directional functional connectivity, paving the way for non-invasive studies investigating information flow between brain regions.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.005
       
  • CaV2.2 Gates Calcium-Independent but Voltage-Dependent Secretion in
           Mammalian Sensory Neurons
    • Authors: Zuying Chai; Changhe Wang; Rong Huang; Yuan Wang; Xiaoyu Zhang; Qihui Wu; Yeshi Wang; Xi Wu; Lianghong Zheng; Chen Zhang; Wei Guo; Wei Xiong; Jiuping Ding; Feipeng Zhu; Zhuan Zhou
      Abstract: Publication date: Available online 30 November 2017
      Source:Neuron
      Author(s): Zuying Chai, Changhe Wang, Rong Huang, Yuan Wang, Xiaoyu Zhang, Qihui Wu, Yeshi Wang, Xi Wu, Lianghong Zheng, Chen Zhang, Wei Guo, Wei Xiong, Jiuping Ding, Feipeng Zhu, Zhuan Zhou
      Action potential induces membrane depolarization and triggers intracellular free Ca2+ concentration (Ca2+)-dependent secretion (CDS) via Ca2+ influx through voltage-gated Ca2+ channels. We report a new type of somatic exocytosis triggered by the action potential per se—Ca2+-independent but voltage-dependent secretion (CiVDS)—in dorsal root ganglion neurons. Here we uncovered the molecular mechanism of CiVDS, comprising a voltage sensor, fusion machinery, and their linker. Specifically, the voltage-gated N-type Ca2+ channel (CaV2.2) is the voltage sensor triggering CiVDS, the SNARE complex functions as the vesicle fusion machinery, the “synprint” of CaV2.2 serves as a linker between the voltage sensor and the fusion machinery, and ATP is a cargo of CiVDS vesicles. Thus, CiVDS releases ATP from the soma while CDS releases glutamate from presynaptic terminals, establishing the CaV2.2-SNARE “voltage-gating fusion pore” as a novel pathway co-existing with the canonical “Ca2+-gating fusion pore” pathway for neurotransmitter release following action potentials in primary sensory neurons.
      Teaser Chai et al. uncover the molecular mechanism and cargo of Ca2+-independent but voltage-dependent secretion (CiVDS). In addition to triggering secretion by Ca2+ influx, the N-type Ca2+ channel gates CiVDS through binding the vesicular fusion machinery for ATP release in pain-sensing neurons.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.10.028
       
  • Divergent Connectivity of Homologous Command-like Neurons Mediates
           Segment-Specific Touch Responses in Drosophila
    • Authors: Suguru Takagi; Benjamin Thomas Cocanougher; Sawako Niki; Dohjin Miyamoto; Hiroshi Kohsaka; Hokto Kazama; Richard Doty Fetter; James William Truman; Marta Zlatic; Albert Cardona; Akinao Nose
      Abstract: Publication date: Available online 30 November 2017
      Source:Neuron
      Author(s): Suguru Takagi, Benjamin Thomas Cocanougher, Sawako Niki, Dohjin Miyamoto, Hiroshi Kohsaka, Hokto Kazama, Richard Doty Fetter, James William Truman, Marta Zlatic, Albert Cardona, Akinao Nose
      Animals adaptively respond to a tactile stimulus by choosing an ethologically relevant behavior depending on the location of the stimuli. Here, we investigate how somatosensory inputs on different body segments are linked to distinct motor outputs in Drosophila larvae. Larvae escape by backward locomotion when touched on the head, while they crawl forward when touched on the tail. We identify a class of segmentally repeated second-order somatosensory interneurons, that we named Wave, whose activation in anterior and posterior segments elicit backward and forward locomotion, respectively. Anterior and posterior Wave neurons extend their dendrites in opposite directions to receive somatosensory inputs from the head and tail, respectively. Downstream of anterior Wave neurons, we identify premotor circuits including the neuron A03a5, which together with Wave, is necessary for the backward locomotion touch response. Thus, Wave neurons match their receptive field to appropriate motor programs by participating in different circuits in different segments.
      Teaser Takagi et al. found that body-location-specific touch responses are mediated by segmentally repeated interneurons that differ in their sensorimotor connectivity, eliciting distinct segment-specific escape behaviors.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.10.030
       
  • Differentiation between Oppositely Oriented Microtubules Controls
           Polarized Neuronal Transport
    • Authors: Roderick P. Tas; Anaël Chazeau; Bas M.C. Cloin; Maaike L.A. Lambers; Casper C. Hoogenraad; Lukas C. Kapitein
      Abstract: Publication date: Available online 30 November 2017
      Source:Neuron
      Author(s): Roderick P. Tas, Anaël Chazeau, Bas M.C. Cloin, Maaike L.A. Lambers, Casper C. Hoogenraad, Lukas C. Kapitein
      Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely. In addition, microtubules with similar orientations and modifications form bundles that bias transport. Importantly, because the plus-end-directed Kinesin-1 selectively interacts with acetylated microtubules, this organization guides this motor out of dendrites and into axons. In contrast, Kinesin-3 prefers tyrosinated microtubules and can enter both axons and dendrites. This separation of distinct microtubule subsets into oppositely oriented bundles constitutes a key architectural principle of the neuronal microtubule cytoskeleton that enables polarized sorting by different motor proteins.
      Teaser Tas et al. use optical nanoscopy to show that dendritic microtubules of opposite orientation differ in stability and composition and recruit different motor proteins. This explains why some motor proteins can move into dendrites while others can only enter axons.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.11.018
       
  • Behavior-Dependent Activity and Synaptic Organization of Septo-hippocampal
           GABAergic Neurons Selectively Targeting the Hippocampal CA3 Area
    • Authors: Abhilasha Joshi; Minas Salib; Tim James Viney; David Dupret; Peter Somogyi
      Abstract: Publication date: Available online 30 November 2017
      Source:Neuron
      Author(s): Abhilasha Joshi, Minas Salib, Tim James Viney, David Dupret, Peter Somogyi
      Rhythmic medial septal (MS) GABAergic input coordinates cortical theta oscillations. However, the rules of innervation of cortical cells and regions by diverse septal neurons are unknown. We report a specialized population of septal GABAergic neurons, the Teevra cells, selectively innervating the hippocampal CA3 area bypassing CA1, CA2, and the dentate gyrus. Parvalbumin-immunopositive Teevra cells show the highest rhythmicity among MS neurons and fire with short burst duration (median, 38 ms) preferentially at the trough of both CA1 theta and slow irregular oscillations, coincident with highest hippocampal excitability. Teevra cells synaptically target GABAergic axo-axonic and some CCK interneurons in restricted septo-temporal CA3 segments. The rhythmicity of their firing decreases from septal to temporal termination of individual axons. We hypothesize that Teevra neurons coordinate oscillatory activity across the septo-temporal axis, phasing the firing of specific CA3 interneurons, thereby contributing to the selection of pyramidal cell assemblies at the theta trough via disinhibition.
      Teaser Using congruent neuronal features, Joshi et al. define the most rhythmic medial septal GABAergic cell type, the Teevra cells, which preferentially innervate axo-axonic GABAergic interneurons in the hippocampal CA3. Such selective termination coordinates hippocampal excitability and theta oscillations via disinhibition.

      PubDate: 2017-12-08T07:34:07Z
      DOI: 10.1016/j.neuron.2017.10.033
       
  • Collective Behavior of Place and Non-place Neurons in the Hippocampal
           Network
    • Authors: Leenoy Meshulam; Jeffrey L. Gauthier; Carlos D. Brody; David W. Tank; William Bialek
      Abstract: Publication date: Available online 16 November 2017
      Source:Neuron
      Author(s): Leenoy Meshulam, Jeffrey L. Gauthier, Carlos D. Brody, David W. Tank, William Bialek
      Discussions of the hippocampus often focus on place cells, but many neurons are not place cells in any given environment. Here we describe the collective activity in such mixed populations, treating place and non-place cells on the same footing. We start with optical imaging experiments on CA1 in mice as they run along a virtual linear track and use maximum entropy methods to approximate the distribution of patterns of activity in the population, matching the correlations between pairs of cells but otherwise assuming as little structure as possible. We find that these simple models accurately predict the activity of each neuron from the state of all the other neurons in the network, regardless of how well that neuron codes for position. Our results suggest that understanding the neural activity may require not only knowledge of the external variables modulating it but also of the internal network state.
      Teaser Correlation patterns in CA1 hippocampus only partially arise from place encoding. Meshulam et al. utilize a population-level modeling approach to uncover collective patterns of activity in CA1 neurons that substantially reflect not only position but also their internal network state.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.027
       
  • Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein
           Kinase A
    • Authors: Yao Chen; Adam J. Granger; Trinh Tran; Jessica L. Saulnier; Alfredo Kirkwood; Bernardo L. Sabatini
      Abstract: Publication date: Available online 16 November 2017
      Source:Neuron
      Author(s): Yao Chen, Adam J. Granger, Trinh Tran, Jessica L. Saulnier, Alfredo Kirkwood, Bernardo L. Sabatini
      Protein kinase A (PKA) integrates inputs from G-protein-coupled neuromodulator receptors to modulate synaptic and cellular function. Gαs signaling stimulates PKA activity, whereas Gαi inhibits PKA activity. Gαq, on the other hand, signals through phospholipase C, and it remains unclear whether Gαq-coupled receptors signal to PKA in their native context. Here, using two independent optical reporters of PKA activity in acute mouse hippocampus slices, we show that endogenous Gαq-coupled muscarinic acetylcholine receptors activate PKA. Mechanistically, this effect is mediated by parallel signaling via either calcium or protein kinase C. Furthermore, multiple Gαq-coupled receptors modulate phosphorylation by PKA, a classical Gαs/Gαi effector. Thus, these results highlight PKA as a biochemical integrator of three major types of GPCRs and necessitate reconsideration of classic models used to predict neuronal signaling in response to the large family of Gαq-coupled receptors.
      Teaser Chen et al. show that hippocampal Gαq-coupled muscarinic receptors activate PKA, an effector classically associated with the Gαs/Gαi pathways. The regulation is mediated by parallel signaling via either Ca2+ or PKC and generalizes to other endogenous and designer Gαq-coupled receptors.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.023
       
  • The Wnt Inhibitor Apcdd1 Coordinates Vascular Remodeling and Barrier
           Maturation of Retinal Blood Vessels
    • Authors: Jenna Mazzoni; Julian R. Smith; Sanjid Shahriar; Tyler Cutforth; Bernardo Ceja; Dritan Agalliu
      Abstract: Publication date: Available online 16 November 2017
      Source:Neuron
      Author(s): Jenna Mazzoni, Julian R. Smith, Sanjid Shahriar, Tyler Cutforth, Bernardo Ceja, Dritan Agalliu
      Coordinating angiogenesis with acquisition of tissue-specific properties in endothelial cells is essential for vascular function. In the retina, endothelial cells form a blood-retina barrier by virtue of tight junctions and low transcytosis. While the canonical Norrin/Fz4/Lrp5/6 pathway is essential for angiogenesis, vascular remodeling, and barrier maturation, how these diverse processes are coordinated remains poorly understood. Here we demonstrate that Apcdd1, a negative regulator of Wnt/β-catenin signaling, is expressed in retinal endothelial cells during angiogenesis and barrier formation. Apcdd1-deficient mice exhibit a transient increase in vessel density at ages P10–P12 due to delayed vessel pruning. Moreover, Apcdd1 mutant endothelial cells precociously form the paracellular component of the barrier. Conversely, mice that overexpress Apcdd1 in retina endothelial cells have reduced vessel density but increased paracellular barrier permeability. Apcdd1 thus serves to precisely modulate Wnt/Norrin signaling activity in the retinal endothelium and coordinate the timing of both vascular pruning and barrier maturation.
      Teaser How Wnt signaling coordinates vascular remodeling and barrier maturation in the retina is poorly understood. Mazzoni et al. demonstrate that mice lacking Apcdd1 exhibit decreased vessel pruning and precocious formation of the blood-retina barrier. Conversely, Apcdd1 overexpression in endothelial cells induces the opposite phenotype. Apcdd1 precisely sculpts Wnt activity to coordinate vascular pruning and barrier maturation.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.025
       
  • Lateral Orbitofrontal Inactivation Dissociates Devaluation-Sensitive
           Behavior and Economic Choice
    • Authors: Matthew P.H. Gardner; Jessica S. Conroy; Michael H. Shaham; Clay V. Styer; Geoffrey Schoenbaum
      Abstract: Publication date: Available online 16 November 2017
      Source:Neuron
      Author(s): Matthew P.H. Gardner, Jessica S. Conroy, Michael H. Shaham, Clay V. Styer, Geoffrey Schoenbaum
      How do we choose between goods that have different subjective values, like apples and oranges' Neuroeconomics proposes that this is done by reducing complex goods to a single unitary value to allow comparison. This value is computed “on the fly” from the underlying model of the goods space, allowing decisions to meet current needs. This is termed “model-based” behavior to distinguish it from pre-determined, habitual, or “model-free” behavior. The lateral orbitofrontal cortex (OFC) supports model-based behavior in rats and primates, but whether the OFC is necessary for economic choice is less clear. Here we tested this question by optogenetically inactivating the lateral OFC in rats in a classic model-based task and during economic choice. Contrary to predictions, inactivation disrupted model-based behavior without affecting economic choice.
      Teaser In the current study, Gardner et al. show that optogenetic inactivation of orbitofrontal cortex has no effect on an economic choice behavior modeled after primate studies. Using the same cohort of rats, they find that inactivation of the OFC does disrupt devaluation-sensitive behavior.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.026
       
  • Discrete Circuits Support Generalized versus Context-Specific Vocal
           Learning in the Songbird
    • Authors: Lucas Y. Tian; Michael S. Brainard
      Abstract: Publication date: Available online 16 November 2017
      Source:Neuron
      Author(s): Lucas Y. Tian, Michael S. Brainard
      Motor skills depend on the reuse of individual gestures in multiple sequential contexts (e.g., a single phoneme in different words). Yet optimal performance requires that a given gesture be modified appropriately depending on the sequence in which it occurs. To investigate the neural architecture underlying such context-dependent modifications, we studied Bengalese finch song, which, like speech, consists of variable sequences of “syllables.” We found that when birds are instructed to modify a syllable in one sequential context, learning generalizes across contexts; however, if unique instruction is provided in different contexts, learning is specific for each context. Using localized inactivation of a cortical-basal ganglia circuit specialized for song, we show that this balance between generalization and specificity reflects a hierarchical organization of neural substrates. Primary motor circuitry encodes a core syllable representation that contributes to generalization, while top-down input from cortical-basal ganglia circuitry biases this representation to enable context-specific learning.
      Teaser Tian and Brainard investigate context-dependent vocal learning in birdsong. They find that learned syllable modifications that differ across sequential contexts reflect sequence-specific biasing from cortical-basal ganglia circuitry, while modifications that generalize reflect changes to a core syllable representation in motor circuitry.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.019
       
  • Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate
           Sema3F-Dependent Homeostatic Scaling in Cortical Neurons
    • Authors: Qiang Wang; Shu-Ling Chiu; Eleftheria Koropouli; Ingie Hong; Sarah Mitchell; Teresa P. Easwaran; Natalie R. Hamilton; Ahleah S. Gustina; Qianwen Zhu; David D. Ginty; Richard L. Huganir; Alex L. Kolodkin
      Abstract: Publication date: Available online 16 November 2017
      Source:Neuron
      Author(s): Qiang Wang, Shu-Ling Chiu, Eleftheria Koropouli, Ingie Hong, Sarah Mitchell, Teresa P. Easwaran, Natalie R. Hamilton, Ahleah S. Gustina, Qianwen Zhu, David D. Ginty, Richard L. Huganir, Alex L. Kolodkin
      Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor mediate homeostatic plasticity in cortical neurons. Sema3F-Npn-2/PlexA3 signaling is essential for cell surface AMPAR homeostatic downscaling in response to an increase in neuronal activity, Npn-2 associates with AMPARs, and Sema3F regulates this interaction. Therefore, Sema3F-Npn-2/PlexA3 signaling controls both synapse development and synaptic plasticity.
      Teaser Regulation of AMPA-type glutamate receptor number at synapses underlies modulation of synaptic strength during homeostatic scaling. Wang et al. show that the secreted protein semaphorin 3F (Sema3F) and its neuropilin-2/plexinA3 holoreceptor mediate homeostatic plasticity in cortical neurons.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.029
       
  • A Local Rebalancing Act Leads to Global Benefit
    • Authors: Zuo
      Abstract: Publication date: 15 November 2017
      Source:Neuron, Volume 96, Issue 4
      Author(s): Ju Lu, Yi Zuo
      Barnes et al. (2017) reveal that in the visual cortex of sensory-deprived mice, dendritic spine enlargement correlates with recent spine loss from the same dendritic branch. Such branch-specific homeostatic plasticity highlights dendritic branches as key computational units.
      Teaser Barnes et al. reveal that in the visual cortex of sensory-deprived mice, dendritic spine enlargement correlates with recent spine loss from the same dendritic branch. Such branch-specific homeostatic plasticity highlights dendritic branches as key computational units.

      PubDate: 2017-11-27T08:57:29Z
       
  • “Silent” NMDA Synapses Enhance Motion Sensitivity in a Mature
           Retinal Circuit
    • Authors: Santhosh Sethuramanujam; Xiaoyang Yao; Geoff deRosenroll; Kevin L. Briggman; Greg D. Field; Gautam B. Awatramani
      Abstract: Publication date: Available online 5 November 2017
      Source:Neuron
      Author(s): Santhosh Sethuramanujam, Xiaoyang Yao, Geoff deRosenroll, Kevin L. Briggman, Greg D. Field, Gautam B. Awatramani
      Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated. Here, we use a combination of paired patch-clamp recordings, serial EM, and large-scale multi-electrode array recordings to show that a single high-sensitivity source of glutamate is processed differentially by starbursts via AMPA receptors and DSGCs via NMDA receptors. We further demonstrate how this novel synaptic arrangement enables DSGCs to encode direction robustly near threshold contrasts. Together, these results reveal a space-efficient synaptic circuit model for direction computations, in which “silent” NMDA receptors play critical roles.
      Teaser Sethuramanujam et al. demonstrate that common bipolar input to DSGCs and GABAergic/cholinergic starburst amacrine cells is differentially processed using NMDA and AMPA receptors, respectively. Results further indicate how this synaptic arrangement enhances the DSGC’s ability to code direction at threshold contrast.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.09.058
       
  • Local Order within Global Disorder: Synaptic Architecture of Visual Space
    • Authors: Benjamin Scholl; Daniel E. Wilson; David Fitzpatrick
      Abstract: Publication date: Available online 2 November 2017
      Source:Neuron
      Author(s): Benjamin Scholl, Daniel E. Wilson, David Fitzpatrick
      Substantial evidence at the subcellular level indicates that the spatial arrangement of synaptic inputs onto dendrites could play a significant role in cortical computations, but how synapses of functionally defined cortical networks are arranged within the dendrites of individual neurons remains unclear. Here we assessed one-dimensional spatial receptive fields of individual dendritic spines within individual layer 2/3 neuron dendrites. Spatial receptive field properties of dendritic spines were strikingly diverse, with no evidence of large-scale topographic organization. At a fine scale, organization was evident: neighboring spines separated by less than 10 μm shared similar spatial receptive field properties and exhibited a distance-dependent correlation in sensory-driven and spontaneous activity patterns. Fine-scale dendritic organization was supported by the fact that functional groups of spines defined by dimensionality reduction of receptive field properties exhibited non-random dendritic clustering. Our results demonstrate that functional synaptic clustering is a robust feature existing at a local spatial scale.
      Teaser Scholl et al. report that the dendritic spines of pyramidal neurons in ferret visual cortex are functionally clustered at a scale of 5–10 μm, exhibiting common visual response properties and correlation in their spontaneous and sensory driven activity.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.017
       
  • Kinetics of Releasable Synaptic Vesicles and Their Plastic Changes at
           Hippocampal Mossy Fiber Synapses
    • Authors: Mitsuharu Midorikawa; Takeshi Sakaba
      Abstract: Publication date: Available online 2 November 2017
      Source:Neuron
      Author(s): Mitsuharu Midorikawa, Takeshi Sakaba
      Hippocampal mossy fiber boutons (hMFBs) are presynaptic terminals displaying various forms of synaptic plasticity. The presynaptic mechanisms underlying synaptic plasticity still remain poorly understood. Here, we have combined high temporal resolution measurements of presynaptic capacitance and excitatory postsynaptic currents (EPSCs) to measure the kinetics of exocytosis. In addition, total internal reflection fluorescence (TIRF) microscopy was employed to directly visualize dynamics of single synaptic vesicles adjacent to the plasma membrane at high spatial resolution. Readily releasable vesicles mostly consisted of already-tethered vesicles in the TIRF field. Vesicle replenishment had fast and slow phases, and TIRF imaging suggests that the fast phase depends on vesicle priming from already-tethered vesicles. Application of cyclic AMP (cAMP), a molecule crucial for LTP, mainly increases the vesicular release probability rather than the number of readily releasable vesicles or their replenishment rate, likely by changing the coupling between Ca2+ channels and synaptic vesicles. Thus, we revealed dynamic properties of synaptic vesicles at hMFBs.
      Teaser Midorikawa and Sakaba combined electrophysiological recordings and total internal reflection microscopy and revealed the dynamics of synaptic vesicles at hippocampal mossy fiber boutons in basal and cAMP-potentiated states, which may be relevant for LTP.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.016
       
  • A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia
    • Authors: Satvinder Kaur; Joshua L. Wang; Loris Ferrari; Stephen Thankachan; Daniel Kroeger; Anne Venner; Michael Lazarus; Andrew Wellman; Elda Arrigoni; Patrick M. Fuller; Clifford B. Saper
      Abstract: Publication date: Available online 2 November 2017
      Source:Neuron
      Author(s): Satvinder Kaur, Joshua L. Wang, Loris Ferrari, Stephen Thankachan, Daniel Kroeger, Anne Venner, Michael Lazarus, Andrew Wellman, Elda Arrigoni, Patrick M. Fuller, Clifford B. Saper
      The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBelCGRP neurons caused wakefulness, whereas optogenetic inhibition of PBelCGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBelCGRP terminals identified a network of forebrain sites under the control of a PBelCGRP switch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea.
      Teaser Kaur et al. identify calcitonin gene-related peptide neurons in the parabrachial nucleus as a key switch for waking up the brain in response to elevated CO2. This switch provides a target for preventing sleep disruptions in obstructive sleep apnea.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.009
       
  • DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of
           Ndel1/Nde1 during Mitosis
    • Authors: Fei Ye; Eunchai Kang; Chuan Yu; Xuyu Qian; Fadi Jacob; Cong Yu; Mao Mao; Randy Y.C. Poon; Jieun Kim; Hongjun Song; Guo-li Ming; Mingjie Zhang
      Abstract: Publication date: Available online 2 November 2017
      Source:Neuron
      Author(s): Fei Ye, Eunchai Kang, Chuan Yu, Xuyu Qian, Fadi Jacob, Cong Yu, Mao Mao, Randy Y.C. Poon, Jieun Kim, Hongjun Song, Guo-li Ming, Mingjie Zhang
      Mutations of DISC1 (disrupted-in-schizophrenia 1) have been associated with major psychiatric disorders. Despite the hundreds of DISC1-binding proteins reported, almost nothing is known about how DISC1 interacts with other proteins structurally to impact human brain development. Here we solved the high-resolution structure of DISC1 C-terminal tail in complex with its binding domain of Ndel1. Mechanistically, DISC1 regulates Ndel1’s kinetochore attachment, but not its centrosome localization, during mitosis. Functionally, disrupting DISC1/Ndel1 complex formation prolongs mitotic length and interferes with cell-cycle progression in human cells, and it causes cell-cycle deficits of radial glial cells in the embryonic mouse cortex and human forebrain organoids. We also observed similar deficits in organoids derived from schizophrenia patient induced pluripotent stem cells (iPSCs) with a DISC1 mutation that disrupts its interaction with Ndel1. Our study uncovers a new mechanism of action for DISC1 based on its structure, and it has implications for how genetic insults may contribute to psychiatric disorders.
      Teaser Ye et al. use structural insights to uncover a functional interaction between psychiatric risk genes, DISC1 and Ndel1/Nde1, in regulating cell-cycle progression of neural stem cells during cortical development.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.010
       
  • Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and
           Inhibits Remyelination after Vascular Damage
    • Authors: Mark A. Petersen; Jae Kyu Ryu; Kae-Jiun Chang; Ainhoa Etxeberria; Sophia Bardehle; Andrew S. Mendiola; Wanjiru Kamau-Devers; Stephen P.J. Fancy; Andrea Thor; Eric A. Bushong; Bernat Baeza-Raja; Catriona A. Syme; Michael D. Wu; Pamela E. Rios Coronado; Anke Meyer-Franke; Stephanie Yahn; Lauriane Pous; Jae K. Lee; Christian Schachtrup; Hans Lassmann; Eric J. Huang; May H. Han; Martina Absinta; Daniel S. Reich; Mark H. Ellisman; David H. Rowitch; Jonah R. Chan; Katerina Akassoglou
      Abstract: Publication date: Available online 2 November 2017
      Source:Neuron
      Author(s): Mark A. Petersen, Jae Kyu Ryu, Kae-Jiun Chang, Ainhoa Etxeberria, Sophia Bardehle, Andrew S. Mendiola, Wanjiru Kamau-Devers, Stephen P.J. Fancy, Andrea Thor, Eric A. Bushong, Bernat Baeza-Raja, Catriona A. Syme, Michael D. Wu, Pamela E. Rios Coronado, Anke Meyer-Franke, Stephanie Yahn, Lauriane Pous, Jae K. Lee, Christian Schachtrup, Hans Lassmann, Eric J. Huang, May H. Han, Martina Absinta, Daniel S. Reich, Mark H. Ellisman, David H. Rowitch, Jonah R. Chan, Katerina Akassoglou
      Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro. Fibrinogen effects are rescued by BMP type I receptor inhibition using dorsomorphin homolog 1 (DMH1) or CRISPR/Cas9 activin A receptor type I (ACVR1) knockout in OPCs. Fibrinogen and the BMP target Id2 are increased in demyelinated multiple sclerosis (MS) lesions. Therapeutic depletion of fibrinogen decreases BMP signaling and enhances remyelination in vivo. Targeting fibrinogen may be an upstream therapeutic strategy to promote the regenerative potential of CNS progenitors in diseases with remyelination failure.
      Teaser Extrinsic inhibitors contribute to remyelination failure in neurological diseases. Petersen et al. identify the blood coagulation factor fibrinogen as an activator of BMP receptor signaling in oligodendrocyte progenitor cells that may be targeted therapeutically to promote remyelination.

      PubDate: 2017-11-27T08:57:29Z
      DOI: 10.1016/j.neuron.2017.10.008
       
 
 
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