Nature Neuroscience Contents: June 2014 Volume 17 Number 6, pp 745 - 889

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TABLE OF CONTENTS June 2014 Volume 17, Issue 6 Focus Editorial News and Views Perspective Reviews Brief Communications Articles Technical Report Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Download the new NatureJournals app and gain access to Nature and all Nature-branded research and review journals. All news content and open access articles are free. Subscribe to additional journals in the app for just $35.99*.  *Apple exchange rates apply. Limited time offer available on all journals except Scientific Reports. iPad, iPhone and iPod touch are trademarks of Apple Inc.   Focus Top Focus on neurogenomics Focus issue: June 2014 Volume 17, No 6 Contents Editorial Perspective Reviews Glossary Editorial Top Focus on neurogenomics   p745 doi:10.1038/nn.3735 Nature Neuroscience presents a series of Perspectives and Reviews highlighting recent advances in understanding the genetics of complex brain disorders. News and Views Top Shedding light on learning   pp746 - 747 Byron M Yu and Steven M Chase doi:10.1038/nn.3723 Brain-computer interfaces (BCIs) and optical imaging have both undergone impressive technological growth in recent years. A study in which mice learn to modulate neural activity merges these technologies to investigate the neural basis of BCI learning with unprecedented spatial detail. See also: Brief Communication by Clancy et al. Impaired import: how huntingtin harms   pp747 - 749 Elizabeth A Jonas doi:10.1038/nn.3726 We now learn that mutant huntingtin binds to a complex that imports constituent proteins across the mitochondrial inner membrane, halting bioenergetics in synaptic mitochondria and predisposing to neuronal dysfunction and death. See also: Article by Yano et al. Is there signal in the noise?   pp750 - 751 Alexander S Ecker and Andreas S Tolias doi:10.1038/nn.3722 A study now shows that variability in neuronal responses in the visual system mainly arises from slow fluctuations in excitability, presumably caused by factors of nonsensory origin, such as arousal, attention or anesthesia. See also: Article by Goris et al. The needle in the haystack   pp752 - 753 Clarissa J Shephard and Garrett B Stanley doi:10.1038/nn.3730 Spike-based approaches to feature selectivity in sensory pathways can bias toward only the most active neurons. A subthreshold method identifies feature selectivity in the rodent vibrissal system regardless of spiking activity. See also: Article by Ramirez et al. The (gamma) power to control our dreams   pp753 - 755 Jessica D Payne doi:10.1038/nn.3727 Stimulating the brain in the gamma frequency range, which is the frequency band most often associated with conscious awareness in the awake state, boosts the ability to engage in lucid dreaming during REM sleep. See also: Brief Communication by Voss et al. Pacemaker's burden   p755 Min Cho doi:10.1038/nn0614-755 Neuroscience JOBS of the week Postdoctoral researcher in molecular and developmental neuroscience VIB Center for the Biology of Disease, K.U.Leuven Postdoctoral Neuroscience Research Positions University of California - Irvine Neuroscience Postdoctoral Fellowships University of California - Davis Postdoc position in Neuroscience Lund University Faculty Positions in Neuroscience, Northeastern University Northeastern University More Science jobs from Neuroscience EVENT Introduction to Neuroinformatics 22.08.14 Leiden, Netherlands More science events from Perspective Top Genome-scale neurogenetics: methodology and meaning   pp756 - 763 Steven A McCarroll, Guoping Feng and Steven E Hyman doi:10.1038/nn.3716 Large-scale collaborative efforts coupled with new genomic technologies now allow reliable detection of genetic variants influencing risk for major psychiatric and neurodevelopmental disorders. In this Perspective the authors provide a primer on current genome-wide efforts to identify risk variants and how these may be translated into neurobiological insights. Reviews Top Prioritization of neurodevelopmental disease genes by discovery of new mutations   pp764 - 772 Alexander Hoischen, Niklas Krumm and Evan E Eichler doi:10.1038/nn.3703 Advances in genome sequencing technologies have revolutionized the search for rare and penetrant mutations leading to diseases such as autism. Given that all individuals carry new and disruptive mutations, in this Review, the authors discuss ways to home in on pathogenic mutations associated with neurodevelopmental disorders. One gene, many neuropsychiatric disorders: lessons from Mendelian diseases   pp773 - 781 Xiaolin Zhu, Anna C Need, Slavé Petrovski and David B Goldstein doi:10.1038/nn.3713 Mutations in Mendelian disease genes often lead to distinct clinical presentations, and the same non-specific risk is now apparent for many neuropsychiatric disorders. In this Review, the authors analyze pathogenic mechanisms for known Mendelian disease and discuss what it means for understanding the causes of non-specific genetic risk in more complex brain diseases. Large-scale genomics unveils the genetic architecture of psychiatric disorders   pp782 - 790 Jacob Gratten, Naomi R Wray, Matthew C Keller and Peter M Visscher doi:10.1038/nn.3708 It is now possible to systematically identify, on a genome-wide scale, genetic variants for disease, how often they occur in the population and how large their impact is on risk. In this Review, the authors discuss recent findings regarding the genetic architecture of psychiatric disorders and the contribution of common but weak and rare but strong variants to disease risk. Whole-genome analyses of whole-brain data: working within an expanded search space   pp791 - 800 Sarah E Medland, Neda Jahanshad, Benjamin M Neale and Paul M Thompson doi:10.1038/nn.3718 Understanding how genetic variation contributes to normal and pathological brain function requires integrating genetic and neuroimaging studies. New imaging consortia now make it possible to systematically assess the impact of genetic variation on the structure and function of the brain on a whole-genome and whole-brain level. In this Review, the authors summarize efforts to combine genome-wide studies with brain imaging and discuss the statistical and methodological issues necessary to insure rigor and robustness in this rapidly developing field. Brief Communications Top The age and genomic integrity of neurons after cortical stroke in humans   pp801 - 803 Hagen B Huttner, Olaf Bergmann, Mehran Salehpour, Attila Racz, Jemal Tatarishvili et al. doi:10.1038/nn.3706 In this study, the authors use measures of carbon-14 in neuronal DNA from human stroke patient cortical tissue samples to show that, unlike previous studies done in rodents, they do not find any evidence of increased neurogenesis after an ischemic injury. In addition, DNA damage assays suggest that there is no increase in DNA rearrangement after this insult. Cellular origins of auditory event-related potential deficits in Rett syndrome   pp804 - 806 Darren Goffin, Edward S Brodkin, Julie A Blendy, Steve J Siegel and Zhaolan Zhou doi:10.1038/nn.3710 Sensory processing deficits are observed in individuals with Rett syndrome and MeCP2-deficient mice. Here, the authors show that it is the loss of MeCP2 specifically in forebrain inhibitory neurons that leads to deficits in auditory-evoked local field potentials and elicits the seizures observed in MeCP2-deficient mice. Volitional modulation of optically recorded calcium signals during neuroprosthetic learning   pp807 - 809 Kelly B Clancy, Aaron C Koralek, Rui M Costa, Daniel E Feldman and Jose M Carmena doi:10.1038/nn.3712 In this paper, Clancy and colleagues introduce an optically driven brain machine interface (BMI) based on the processing of optical calcium signals recorded using two-photon microscopy. When applied to mouse cortex, this approach revealed that learning in a BMI-mediated operant task is accompanied by the progressive spatial refinement of activity in local networks comprising output-relevant neurons. See also: News and Views by Yu & Chase Induction of self awareness in dreams through frontal low current stimulation of gamma activity   pp810 - 812 Ursula Voss, Romain Holzmann, Allan Hobson, Walter Paulus, Judith Koppehele-Gossel et al. doi:10.1038/nn.3719 Lucid dreaming, in which the sleeper is aware of the dream state, has been associated with increased neural activity around 40 Hz (lower gamma band), but their causal relationship remains unclear. The authors show that, during REM sleep, fronto-temporal transcranial stimulation in the lower gamma band can induce lucid dreaming. See also: News and Views by Payne Articles Top Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes   pp813 - 821 Sachin Katyal, Youngsoo Lee, Karin C Nitiss, Susanna M Downing, Yang Li et al. doi:10.1038/nn.3715 In this study, the authors show that topoisomerase-1-DNA cleavage complex (Top1cc) accumulation may be involved in the onset of ataxia telangiectasia and spinocerebellar ataxia with axonal neuropathy 1. In addition, they find that ATM regulates Top1cc levels in a kinase activity- and double-stranded break repair-independent manner. Inhibition of mitochondrial protein import by mutant huntingtin   pp822 - 831 Hiroko Yano, Sergei V Baranov, Oxana V Baranova, Jinho Kim, Yanchun Pan et al. doi:10.1038/nn.3721 Mitochondrial dysfunction has been associated with Huntington's disease. The authors show that mutant huntingtin binds to the mitochondrial import protein TIM23, leading to a deficit in import. Overexpression of TIM23 subunits partially rescued the import defect and subsequent neuronal death. See also: News and Views by Jonas Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase   pp832 - 840 Javier Sanchez-Padilla, Jaime N Guzman, Ema Ilijic, Jyothisri Kondapalli, Daniel J Galtieri et al. doi:10.1038/nn.3717 Noradrenergic neurons in the locus coeruleus (LC) are known to undergo degeneration in Parkinson's and Alzheimer's diseases. LC neurons may be under bioenergetic constraints due to spontaneous spiking. Here, Sanchez-Padilla et al. show that calcium entry through L-type channels during spiking of LC neurons creates mitochondrial oxidant and nitrosative stress. The study also demonstrates increased LC vulnerability in a mouse model of Parkinson's disease. Scaling down of balanced excitation and inhibition by active behavioral states in auditory cortex   pp841 - 850 Mu Zhou, Feixue Liang, Xiaorui R Xiong, Lu Li, Haifu Li et al. doi:10.1038/nn.3701 The authors report that in mouse auditory cortex, the sensory-evoked spike responses of layer 2/3 (L2/3) excitatory cells were scaled down with preserved sensory tuning when animals transitioned from quiescence to active behaviors, while L4 and thalamic responses were unchanged. This laminar-specific gain control could be attributed to an enhancement of L1-mediated inhibition. Population code in mouse V1 facilitates readout of natural scenes through increased sparseness   pp851 - 857 Emmanouil Froudarakis, Philipp Berens, Alexander S Ecker, R James Cotton, Fabian H Sinz et al. doi:10.1038/nn.3707 The authors recorded populations of up to 500 neurons in the mouse primary visual cortex during natural movies. They found that higher-order correlations in natural scenes induce a sparser code, with reliable activation of a smaller set of neurons that can be read out more easily, but only in anesthetized and active awake animals, not during quiet wakefulness. Partitioning neuronal variability   pp858 - 865 Robbe L T Goris, J Anthony Movshon and Eero P Simoncelli doi:10.1038/nn.3711 The authors developed a model of neuron firing in which spike generation arises from the combination of sensory drive and stimulus-independent modulatory influences. This model provides an accurate account of neuron responses in multiple visual areas, suggesting that variability originates from excitability fluctuations that increase in strength along the visual pathway. See also: News and Views by Ecker & Tolias Spatiotemporal receptive fields of barrel cortex revealed by reverse correlation of synaptic input   pp866 - 875 Alejandro Ramirez, Eftychios A Pnevmatikakis, Josh Merel, Liam Paninski, Kenneth D Miller et al. doi:10.1038/nn.3720 To investigate the sensory contributions of barrel cortex, the authors estimate spatiotemporal receptive fields by reverse correlation of multi-whisker stimulation to synaptic inputs. Complex stimuli revealed dramatically sharpened receptive fields, largely due to adaptation, and suggest the potential importance of surround facilitation through adaptation for discriminating complex shapes and textures during natural sensing. See also: News and Views by Shephard & Stanley Executive control processes underlying multi-item working memory   pp876 - 883 Antonio H Lara and Jonathan D Wallis doi:10.1038/nn.3702 The authors recorded activity of prefrontal cortex neurons in monkeys performing a multi-item color change detection task and found that neurons reported information about the item's position and the location covert attention, but not its color. Increased power in the local field potential correlated with more precise color representations. Taken together, these results suggest that PFC controls the allocation of resources in working memory. Technical Report Top High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor   pp884 - 889 François St-Pierre, Jesse D Marshall, Ying Yang, Yiyang Gong, Mark J Schnitzer et al. doi:10.1038/nn.3709 In this technical report, St-Pierre and colleagues introduce a new genetically encoded voltage sensor called Accelerated Sensor of Action Potentials 1 (ASAP1), which consists of a circularly permuted GFP inserted in the extracellular voltage-sensing domain of a phosphatase. ASAP1 surpasses existing sensors in reliably detecting single action potentials and tracking subthreshold potentials and high-frequency spike trains. Top Advertisement Nature Reviews Neurology  Focus on Epilepsy  In this special focus issue, cutting-edge investigators from around the world highlight the important challenges and progress in epilepsy research and clinical practice. 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