Nature Neuroscience Contents: November 2015 Volume 18 Number 11, pp 1531 - 1697

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Advertisement Nikon's A1RMP+ multiphoton system is now available with a New Dual IR beam option. With dual IR beams, users can now simultaneously excite two different fluorophores such as GFP and mCherry. This capability enables ultra-fast two-color multiphoton imaging, ideal for dynamic specimens. To learn more, please visit www.nikoninstruments.com/a1rmp TABLE OF CONTENTS November 2015 Volume 18, Issue 11 Obituary News and Views Perspective Review Brief Communications Articles Resource Advertisement Dr. Amar Thyagarajan discussed with Nature the importance of the development of mouse and rat models and how they solve scientific challenges facing neuroscientists today.  Click here to read his :insideview. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Make your experiments glow with Brainbow! Brainbow is a genetic cell-labeling technique in modern neuroscience where individual neurons in the brain can be distinguished from neighboring neurons using spectrally distinct fluorescent proteins. Start your Brainbow experiments with the right controls, by using Rockland's anti-GFP and anti-RFP antibodies or try our GFP Western Blot kit in your protein expression experiments after cloning or if you need to immune precipitate your proteins.  Click here to learn more about #Brainbow!   Advertisement Primers in your inbox Nature Reviews Disease Primers launched in April 2015 and publishes Primers — introductory review articles that provide overviews of diseases and disorders. Primer articles describe all aspects of a condition: epidemiology; disease mechanisms; diagnosis, screening and prevention; management; and quality of life.  Stay updated on the latest Primers published.     Advertisement The Naturejobs Career Expo is coming to Düsseldorf for the first time on 26 November! This career fair offers young, talented researchers an excellent opportunity to meet a diverse selection of national and international employers from academic institutions and scientific industries. The event is free and offers you a chance to meet and network with employers and leading scientific institutions and attend useful workshops.  Register and find out more.     Obituary Top Oliver Sacks 1933-2015   p1531 Michael S Gazzaniga doi:10.1038/nn.4149 News and Views Top From phenotypic chaos to neurobiological order   pp1532 - 1534 Avram J Holmes and B T Thomas Yeo doi:10.1038/nn.4145 Complex demographic and behavioral phenotypes can arise from coordinated interactions among brain systems. A single axis of co-variation spanning 'negative' and 'positive' attributes links diverse participant characteristics with specific patterns of brain connectivity. See also: Brief Communication by Smith et al. Pore dilation reconsidered   pp1534 - 1535 Bruce P Bean doi:10.1038/nn.4148 Previous experiments have suggested that many P2X family channels undergo a time-dependent process of pore dilation when activated by ATP. Li et al. now propose a different interpretation of the key experiments. See also: Article by Li et al. Ephrin-B3 recruits PSD-95 to synapses   pp1535 - 1537 Erkang Fei, Wen-Cheng Xiong and Lin Mei doi:10.1038/nn.4147 A study now demonstrates that ephrin-B3 recruits and stabilizes PSD-95 at excitatory synapses by direct interaction. Unusually, phosphorylation of ephrin-B3, elicited by neuron depolarization, inhibits this interaction. See also: Article by Hruska et al. The cellular target of antidepressants   pp1537 - 1538 Nicholas J Brandon and Ron McKay doi:10.1038/nn.4144 The serotonin 1A receptor expressed on mature granule cells in the dentate gyrus mediates the behavioral, neurogenic and endocrine effects of the antidepressant fluoxetine in the mouse. See also: Article by Samuels et al. Rethinking canonical cortical circuits   p1538 Neel T Dhruv doi:10.1038/nn1115-1538 See also: Article by Pluta et al. Neuroscience JOBS of the week Sussex Neuroscience 4-Year PhD Programme University of Sussex Assistant Professor of Cell Biology and Neuroscience Rutgers University Neuroscience Postdoctoral Programme Linköping University (LiU) Postdoctoral Scholar: Presidential Scholars in Society and Neuroscience Columbia University Postdoctoral Fellow � Department of Neuroscience Mayo Clinic, Jacksonville More Science jobs from Neuroscience EVENT Microglia in the Brain –16 June 2016 Keystone, USA More science events from Perspective Top Do glia drive synaptic and cognitive impairment in disease?   pp1539 - 1545 Won-Suk Chung, Christina A Welsh, Ben A Barres and Beth Stevens doi:10.1038/nn.4142 There is growing realization that glia actively signal with neurons and influence synaptic development, transmission and plasticity through an array of secreted and contact-dependent signals. We propose that disruptions in neuron-glia signaling contribute to synaptic and cognitive impairment in disease. Review Top Measuring macroscopic brain connections in vivo   pp1546 - 1555 Saad Jbabdi, Stamatios N Sotiropoulos, Suzanne N Haber, David C Van Essen and Timothy E Behrens doi:10.1038/nn.4134 Measuring brain connections in humans continues to pose challenges despite the recent advances in MRI technology. The authors contrast methods used in humans with those used in animals and show the extent to which human techniques can inform us about connections despite their limitations. Brief Communications Top CD33 modulates TREM2: convergence of Alzheimer loci   pp1556 - 1558 Gail Chan, Charles C White, Phoebe A Winn, Maria Cimpean, Joseph M Replogle et al. doi:10.1038/nn.4126 This protein quantitative trait analysis in monocytes evaluates cross-talk between Alzheimer risk loci and finds that the NME8 locus influences PTK2B, the CD33 risk allele leads to greater TREM2 expression, and the TREM1 risk allele is associated with a decreased TREM1/TREM2 ratio. Persistence of Aβ seeds in APP null mouse brain   pp1559 - 1561 Lan Ye, Sarah K Fritschi, Juliane Schelle, Ulrike Obermüller, Karoline Degenhardt et al. doi:10.1038/nn.4117 Misfolded Aβ proteins can form proteopathic seeds that drive initiation, progression, and spreading of amyloidosis in the brain. Jucker and colleagues report that Aβ seeds can persist in mouse brain for months in the absence of host-derived Aβ and can then regain propagative and pathogenic activity in the presence of host Aβ. Memory hierarchies map onto the hippocampal long axis in humans   pp1562 - 1564 Silvy H P Collin, Branka Milivojevic and Christian F Doeller doi:10.1038/nn.4138 The authors show that episodic-memory representations progressively increase in scale along the hippocampal long axis, akin to the gradient of encoded space in the rodent hippocampus. They propose that this coding mechanism may enable the formation of memory hierarchies. A positive-negative mode of population covariation links brain connectivity, demographics and behavior   pp1565 - 1567 Stephen M Smith, Thomas E Nichols, Diego Vidaurre, Anderson M Winkler, Timothy E J Behrens et al. doi:10.1038/nn.4125 Using data from the Human Connectome Project, a single holistic multivariate analysis identified one strong mode of population co-variation: subjects were predominantly spread along a single 'positive-negative' axis linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of functional brain connectivity. See also: News and Views by Holmes & Yeo Neurons in the human amygdala encode face identity, but not gaze direction   pp1568 - 1570 Florian Mormann, Johannes Niediek, Oana Tudusciuc, Carlos M Quesada, Volker A Coenen et al. doi:10.1038/nn.4139 The amygdala is known to process information about faces, but it has remained unclear whether eye gaze is also encoded. Recording single neurons in the amygdalae of neurosurgical patients, the authors found responses to identity of the faces, but not to gaze direction. Neural mechanisms supporting maladaptive food choices in anorexia nervosa   pp1571 - 1573 Karin Foerde, Joanna E Steinglass, Daphna Shohamy and B Timothy Walsh doi:10.1038/nn.4136 Anorexia nervosa provides a compelling example of persistent maladaptive behavior: the severe restriction of caloric intake. Activity in the dorsal striatum was greater in patients than in controls during food choice and correlated with subsequent caloric intake, suggesting that dorsal fronto-striatal circuits are involved in this disorder. Perceptual learning in autism: over-specificity and possible remedies   pp1574 - 1576 Hila Harris, David Israeli, Nancy Minshew, Yoram Bonneh, David J Heeger et al. doi:10.1038/nn.4129 People with autism are known for their inflexible behavior. Using a perceptual learning protocol, the authors demonstrate initially efficient learning in observers with autism, followed by anomalously poor learning when the target location is changed (over-specificity). Furthermore, over-specificity can be circumvented by a specifically designed protocol that reduces stimulus repetitions. Articles Top Physical basis of apparent pore dilation of ATP-activated P2X receptor channels   pp1577 - 1583 Mufeng Li, Gilman E S Toombes, Shai D Silberberg and Kenton J Swartz doi:10.1038/nn.4120 The prevailing view for purinergic P2X receptor channels is that their ion conduction pores dilate upon prolonged activation. This study finds that the hallmark shift in equilibrium potential observed with prolonged channel activation does not result from pore dilation, but from time-dependent alterations in the concentration of intracellular ions. See also: News and Views by Bean Depletion of microglia and inhibition of exosome synthesis halt tau propagation   pp1584 - 1593 Hirohide Asai, Seiko Ikezu, Satoshi Tsunoda, Maria Medalla, Jennifer Luebke et al. doi:10.1038/nn.4132 In this study, the authors show that microglia play an important role in the propagation of pathogenic tau protein. In addition, the authors find that spread of the tau protein occurs via exosome secretion from these microglial cells. Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3   pp1594 - 1605 Martin Hruska, Nathan T Henderson, Nan L Xia, Sylvain J Le Marchand and Matthew B Dalva doi:10.1038/nn.4140 PSD-95 is one of the most abundant proteins at synapses and underlies synapse development and function. Hruska and colleagues show that the synaptic localization and turnover of PSD-95 relies on a direct interaction with the trans-synaptic organizer ephrin-B3, which is negatively regulated by neuronal activity through MAPK-dependent phosphorylation of ephrin-B3. See also: News and Views by Fei et al. 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response   pp1606 - 1616 Benjamin Adam Samuels, Christoph Anacker, Alice Hu, Marjorie R Levinstein, Anouchka Pickenhagen et al. doi:10.1038/nn.4116 Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Using a combination of different approaches, the authors demonstrate that serotonin 1A receptors expressed in mature dentate gyrus granule cells are critical mediators of the response to SSRIs. See also: News and Views by Brandon & McKay Human mutant huntingtin disrupts vocal learning in transgenic songbirds   pp1617 - 1622 Wan-chun Liu, Jessica Kohn, Sarah K Szwed, Eben Pariser, Sharon Sepe et al. doi:10.1038/nn.4133 The study of speech or vocal disorder resulting from neurological diseases lacks a model capable of recapitulating vocal learning. This study suggests that the vocal disorder associated with Huntington's disease is observed in transgenic zebra finches carrying the full-length human mutant huntingtin gene. Rescue of long-range circuit dysfunction in Alzheimer's disease models   pp1623 - 1630 Marc Aurel Busche, Maja Kekus, Helmuth Adelsberger, Takahiro Noda, Hans Forstl et al. doi:10.1038/nn.4137 Sleeping mammalian brains show high coherence of slow-wave activity. In mouse models of Alzheimer's disease, which have abnormal levels of amyloid-β, amyloid plaques and associated memory deficits, these waves are massively impaired. This impairment is related to the previously demonstrated neuronal hyperactivity. Pharmacological manipulations that reduce hyperactivity result in the reinstatement of slow-wave coherence and in memory improvement. A direct translaminar inhibitory circuit tunes cortical output   pp1631 - 1640 Scott Pluta, Alexander Naka, Julia Veit, Gregory Telian, Lucille Yao et al. doi:10.1038/nn.4123 Optogenetic suppression of layer 4 in the sensory cortex reveals a surprising role for its activity in the cortical microcircuit: layer 4 suppresses the main cortical output layer—layer 5—through a direct translaminar inhibitory circuit. This translaminar inhibition sharpens spatial representations in the somatosensory cortex. See also: News and Views by Dhruv Basal forebrain circuit for sleep-wake control   pp1641 - 1647 Min Xu, Shinjae Chung, Siyu Zhang, Peng Zhong, Chenyan Ma et al. doi:10.1038/nn.4143 The basal forebrain (BF) is important for sleep-wake control. In this study, the authors performed cell type-specific recording and manipulation of four genetically defined BF cell types in freely moving mice and mapped their synaptic connections in slices, providing a BF circuit diagram for sleep-wake control. Flexible gating of contextual influences in natural vision   pp1648 - 1655 Ruben Coen-Cagli, Adam Kohn and Odelia Schwartz doi:10.1038/nn.4128 Contextual modulation is ubiquitous in sensory processing. This study shows that, in visual cortex, spatial contextual modulation for natural inputs is not well described by existing models. Instead, it can be explained by inference about statistical structure in images, with modulation evident only when images contain spatial redundancies. Reward expectation differentially modulates attentional behavior and activity in visual area V4   pp1656 - 1663 Jalal K Baruni, Brian Lau and C Daniel Salzman doi:10.1038/nn.4141 Increased signal-to-noise in neural representations of sensory stimuli is thought to underlie the perceptual benefits of attention. Manipulating reward contingencies across two locations dissociates visual cortical activity from attentional behavior. These data argue that attention works by selecting and filtering the relevant and irrelevant information represented in visual cortex. Functional connectome fingerprinting: identifying individuals using patterns of brain connectivity   pp1664 - 1671 Emily S Finn, Xilin Shen, Dustin Scheinost, Monica D Rosenberg, Jessica Huang et al. doi:10.1038/nn.4135 This study shows that every individual has a unique pattern of functional connections between brain regions. This functional connectivity profile acts as a 'fingerprint' that can accurately identify the individual from a large group. Furthermore, an individual's connectivity profile can predict his or her level of fluid intelligence. Negligible fronto-parietal BOLD activity accompanying unreportable switches in bistable perception   pp1672 - 1678 Jan Brascamp, Randolph Blake and Tomas Knapen doi:10.1038/nn.4130 The human ability to choose relies considerably on frontoparietal association cortex. Constructing unified perception from inconclusive sensory input also requires selection among alternatives. Combining fMRI with a novel visual stimulus, Brascamp and colleagues find evidence against frontoparietal involvement in such perceptual selection, instead suggesting choice capability in the visual system itself. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep   pp1679 - 1686 Bernhard P Staresina, Til Ole Bergmann, Mathilde Bonnefond, Roemer van der Meij, Ole Jensen et al. doi:10.1038/nn.4119 New memory traces are believed to be reactivated and reorganized during sleep, mediated by the fine-tuned temporal interplay of neocortical slow oscillations, thalamo-cortical spindles and hippocampal ripples. The authors used intracranial recordings in humans to provide, for the first time, direct evidence for a systematic interaction of these oscillations in the human hippocampus. Resource Top Connectivity of mouse somatosensory and prefrontal cortex examined with trans-synaptic tracing   pp1687 - 1697 Laura A DeNardo, Dominic S Berns, Katherine DeLoach and Liqun Luo doi:10.1038/nn.4131 The authors used trans-synaptic tracing to examine and compare circuit anatomy in mouse barrel and medial prefrontal cortex, revealing novel organizational features and contrasts between the two areas. Notably, medial prefrontal layer 5 neurons receive more long-distance inputs and more local inhibitory inputs than layer 5 neurons in barrel cortex. Top Advertisement Nature Outlook Cannabis Cannabis is undergoing a resurgence of botanical and biomedical interest, spurred by claims of its therapeutic benefits. Yet research into these claims lags behind the legislation that allows medical marijuana use. 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