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- Phenotypic study data and neurological assessments supporting these models.
- Unique aspects of schizophrenia-related biology represented by these three mouse models
- How to use mouse models of neuropsychiatric disease to explore the underlying mechanisms of various disorders
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TABLE OF CONTENTS |
December 2016 Volume 19, Issue 12 |
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 | Editorial News and Views Q&A Review Brief Communications Articles Resource Technical Report
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Nature Outlook: Parkinson's disease
It is 200 years since Parkinson's disease was first described. This Outlook charts the progress of research in an engaging timeline and shows how our understanding of Parkinson's motor and non-motor symptoms has evolved. It also reveals the exciting new applications of smartphones in monitoring the disease.
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Editorial | Top |
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Viewpoints: an interactive forum for debates and discussions p1537 doi:10.1038/nn.4453 Neuroscientists dedicate themselves to understanding the brain. But what happens when they disagree on experimental outcomes, data interpretation or methodology? Nature Neuroscience debuts a format that invites researchers to debate critical issues in neuroscience.
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News and Views | Top |
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Q&A | Top |
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Viewpoints: Dialogues on the functional role of the ventromedial prefrontal cortex pp1545 - 1552 Mauricio R Delgado, Jennifer S Beer, Lesley K Fellows, Scott A Huettel, Michael L Platt et al. doi:10.1038/nn.4438 The ventromedial prefrontal cortex is attributed with various functions during valuation, affect regulation and social cognition. Nature Neuroscience asked a moderator to lead researchers in a dialogue on shared and distinct viewpoints of this region's roles.
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Review | Top |
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Functional and structural underpinnings of neuronal assembly formation in learning pp1553 - 1562 Anthony Holtmaat and Pico Caroni doi:10.1038/nn.4418 Functional studies of neuronal assemblies that encode memories have progressed dramatically due to recent technological advances. This review shows how a focus on assembly formation and consolidation provides a powerful conceptual framework to relate mechanistic studies of synaptic, neuronal and circuit plasticity to behaviorally relevant aspects of learning and memory.
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Brief Communications | Top |
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Ultra-rare disruptive and damaging mutations influence educational attainment in the general population pp1563 - 1565 Andrea Ganna, Giulio Genovese, Daniel P Howrigan, Andrea Byrnes, Mitja I Kurki et al. doi:10.1038/nn.4404 Rare genetic mutations that disrupt the functionality of important genes increase the risk of psychiatric and neurodevelopmental disorder. This study found that, in the general population not diagnosed with such disorders, these same mutations affect the average educational level. Carriers of these mutations have on average half a semester less of education than noncarriers.
See also: News and Views by Cesarini
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Gravity orientation tuning in macaque anterior thalamus pp1566 - 1568 Jean Laurens, Byounghoon Kim, J David Dickman and Dora E Angelaki doi:10.1038/nn.4423 The authors describe neurons in the macaque anterior thalamus tuned to pitch and roll orientation relative to gravity, independently of visual landmarks. Individual cells exhibit two-dimensional tuning curves peaking at a preferred vertical orientation. These results identify a thalamic pathway for gravity cues to influence three-dimensional spatial orientation.
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Nature Insight: Neurodegenerative Diseases This Insight explores brain ageing and possible rejuvenation and updates our understanding of Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease. It also discusses how knowledge from prion disease may apply to more common neurodegenerative disorders and provides a structural perspective on the properties of amyloids. Access the Insight free online Produced with support from: Eli Lilly and Company | | |
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Articles | Top |
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Novel genetic loci underlying human intracranial volume identified through genome-wide association pp1569 - 1582 Hieab H H Adams, Derrek P Hibar, Vincent Chouraki, Jason L Stein, Paul A Nyquist et al. doi:10.1038/nn.4398 In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.
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L1-associated genomic regions are deleted in somatic cells of the healthy human brain pp1583 - 1591 Jennifer A Erwin, Apua C M Paquola, Tatjana Singer, Iryna Gallina, Mark Novotny et al. doi:10.1038/nn.4388 The healthy human brain is a mosaic of varied genomes. Using a single cell sequencing approach targeting L1 elements, the authors show that the contribution of L1 to somatic mosaicism goes beyond retrotransposition and includes deletion of genomic regions associated with L1.
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Mechanosensing is critical for axon growth in the developing brain pp1592 - 1598 David E Koser, Amelia J Thompson, Sarah K Foster, Asha Dwivedy, Eva K Pillai et al. doi:10.1038/nn.4394 Much of what is known about nervous system development is based on chemical signaling. In this study, Koser et al. demonstrate that developing neurons also respond to mechanical signals and that local tissue stiffness is a regulator of neuronal growth in vivo.
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An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage pp1599 - 1609 Makoto Inoue, Po-han Chen, Stephen Siecinski, Qi-jing Li, Chunlei Liu et al. doi:10.1038/nn.4421 Experimental autoimmune encephalomyelitis can be induced by strong activation of innate immunity. This subtype of EAE is resistant to interferon (IFN)-β treatment and is NLRP3 inflammasome independent. Its development is dependent upon lymphotoxin-β receptor LTβR and CXCR2, and can be inhibited by blocking these receptors. The IFNβ-resistant EAE subtype is characterized by minimal remission and neuronal damage induced by semaphorin-6B on CD4+ T cells.
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C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons pp1610 - 1618 Rajeeve Sivadasan, Daniel Hornburg, Carsten Drepper, Nicolas Frank, Sibylle Jablonka et al. doi:10.1038/nn.4407 In this study, Sivadasan et al. show that the interactome of the C9ORF72 protein contains cofilin and other actin-binding proteins. They also demonstrate that actin dynamics are reduced in patient-derived motor neurons and tissues with ALS-related intronic expansion of the C9ORF72 gene, leading to altered axon growth and growth cone dynamics.
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Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles pp1619 - 1627 Anusha Mishra, James P Reynolds, Yang Chen, Alexander V Gourine, Dmitri A Rusakov et al. doi:10.1038/nn.4428 Active neurons increase their energy supply by dilating nearby arterioles and capillaries to increase blood flow, but the mechanisms underlying neurovascular coupling are debated. In this paper, the authors show that different calcium-dependent signaling pathways regulate blood flow at the level of capillary pericytes and arteriole smooth muscle.
See also: News and Views by Rungta & Charpak
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Dynamic GABAergic afferent modulation of AgRP neurons pp1628 - 1635 Alastair S Garfield, Bhavik P Shah, Christian R Burgess, Monica M Li, Chia Li et al. doi:10.1038/nn.4392 AgRP neurons of the arcuate nucleus of the hypothalamus promote homeostatic feeding yet are rapidly suppressed by food-related sensory cues. The authors identify a population of inhibitory DMH-LepR neurons that relays real-time information about the nature and availability of food to dynamically modulate ARC-AgRP neuron activity and feeding behavior.
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Antagonistic negative and positive neurons of the basolateral amygdala pp1636 - 1646 Joshua Kim, Michele Pignatelli, Sangyu Xu, Shigeyoshi Itohara and Susumu Tonegawa doi:10.1038/nn.4414 The authors identify two genetic markers defining non-overlapping populations of principal cells in the amygdala that respond to stimuli of opposite valence. These two populations of cells contribute to behavioral responses to aversive or rewarding experiences, are distributed along antero-posterior gradients that run in opposite directions, and synaptically suppress each other.
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Layer 4 fast-spiking interneurons filter thalamocortical signals during active somatosensation pp1647 - 1657 Jianing Yu, Diego A Gutnisky, S Andrew Hires and Karel Svoboda doi:10.1038/nn.4412 During tactile exploration, neural activity related to movement of digits or whiskers is suppressed to facilitate high signal-to-noise ratio encoding of touch. The authors show that in mouse this computation occurs in layer 4 of the barrel cortex and is mediated by fast-spiking interneurons.
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Experience-dependent spatial expectations in mouse visual cortex pp1658 - 1664 Aris Fiser, David Mahringer, Hassana K Oyibo, Anders V Petersen, Marcus Leinweber et al. doi:10.1038/nn.4385 The authors find that activity in rodent visual cortex can depend on the animal's location in a virtual environment and can predict upcoming visual stimuli. Omitting a stimulus that a mouse expects to see results in a strong mismatch signal, implying that visual cortex compares visual signals to expectations in familiar environments.
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Unstable neurons underlie a stable learned behavior pp1665 - 1671 William A Liberti III, Jeffrey E Markowitz, L Nathan Perkins, Derek C Liberti, Daniel P Leman et al. doi:10.1038/nn.4405 Sleep rearranges the firing patterns of excitatory projection neurons in zebra finch songbirds. Patterned inhibition is implicated in maintaining stable songs in spite of the instability in the projection neuron population.
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History-dependent variability in population dynamics during evidence accumulation in cortex pp1672 - 1681 Ari S Morcos and Christopher D Harvey doi:10.1038/nn.4403 The authors developed experimental and computational approaches to study moment-to-moment changes in the activity of populations of cortical neurons as mice accumulated evidence during decision-making in virtual reality. They propose that evidence accumulation may not require winner-take-all competitions but instead emerges from general dynamical properties that instantiate short-term memory.
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Neural substrate of dynamic Bayesian inference in the cerebral cortex pp1682 - 1689 Akihiro Funamizu, Bernd Kuhn and Kenji Doya doi:10.1038/nn.4390 The ability to estimate environmental state under limited sensory observation is essential for many behaviors and can be realized using dynamic Bayesian inference. The authors use in vivo two-photon calcium imaging and probabilistic population decoding to show that cortical neurons implement prediction and updating, the fundamental features of dynamic Bayesian inference.
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Synaptic scaling rule preserves excitatory-inhibitory balance and salient neuronal network dynamics pp1690 - 1696 Jérémie Barral and Alex D Reyes doi:10.1038/nn.4415 In neuronal cultures, synaptic strengths scale with the network size to preserve balance between excitation and inhibition, maintain variable spiking statistics and reduce correlations in spiking as predicted by theory and observed in the intact brain.
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Computational principles of synaptic memory consolidation pp1697 - 1706 Marcus K Benna and Stefano Fusi doi:10.1038/nn.4401 The biological mechanisms underlying memory are complex and typically involve multiple molecular processes operating on timescales ranging from fractions of a second to years. The authors show using a mathematical model of synaptic plasticity and consolidation that this complexity can help explain the formidable memory capacity of biological systems.
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Global dynamics of selective attention and its lapses in primary auditory cortex pp1707 - 1717 Peter Lakatos, Annamaria Barczak, Samuel A Neymotin, Tammy McGinnis, Deborah Ross et al. doi:10.1038/nn.4386 The authors demonstrate that attention slowly fluctuates at a rhythm that resembles resting-state oscillations. During periods of attention, the brain aligns its neuronal oscillations and the cortical operations they orchestrate to the timing of external stimuli, while attentional lapses are characterized by operations aligned to internally timed alpha oscillations.
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Activity flow over resting-state networks shapes cognitive task activations pp1718 - 1726 Michael W Cole, Takuya Ito, Danielle S Bassett and Douglas H Schultz doi:10.1038/nn.4406 Resting-state functional connectivity has helped reveal the brain's network organization, yet its relevance to cognitive task activations has been unclear. The authors found that estimating activity flow over resting-state networks allows prediction of held-out activations, suggesting activity flow as a linking mechanism between resting-state networks and cognitive task activations.
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The brain adapts to dishonesty pp1727 - 1732 Neil Garrett, Stephanie C Lazzaro, Dan Ariely and Tali Sharot doi:10.1038/nn.4426 In this paper, the authors show that dishonesty gradually increases with repetition. This escalation is supported by a reduction in response to self-serving dishonesty over time in the amygdala.
See also: News and Views by Engelmann & Fehr
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Poster on Molecular mechanisms of amyotrophic lateral sclerosis This poster from Nature Reviews Neuroscience provides an overview of the molecular and cellular mechanisms that have been proposed to contribute to the pathogenesis of amyotrophic lateral sclerosis, which is the most common form of motor neuron disease. Download free online Funded by a grant from MT Pharma America, Inc | | |
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Organization of long-range inputs and outputs of frontal cortex for top-down control pp1733 - 1742 Siyu Zhang, Min Xu, Wei-Cheng Chang, Chenyan Ma, Johnny Phong Hoang Do et al. doi:10.1038/nn.4417 Top-down control is important for sensory processing. In this study, the authors used virus-assisted circuit mapping to identify the brain networks for top-down modulation of multiple sensory modalities and the subnetworks within the visual network, thus providing an anatomical foundation for understanding the brain mechanisms underlying top-down control of behavior.
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Technical Report | Top |
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A viral strategy for targeting and manipulating interneurons across vertebrate species pp1743 - 1749 Jordane Dimidschstein, Qian Chen, Robin Tremblay, Stephanie L Rogers, Giuseppe-Antonio Saldi et al. doi:10.1038/nn.4430 The ability to target and manipulate specific neuronal populations is crucial for understanding brain function. In this report, the authors describe a novel virus that restricts gene expression to telencephalic GABAergic interneurons, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in mice and in non-genetically tractable species.
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