Tuesday, November 29, 2016

Nature Neuroscience Contents: December 2016 Volume 19 Number 12, pp 1537 - 1749

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Nature Neuroscience

  • 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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December 2016 Volume 19, Issue 12

News and Views
Brief Communications
Technical Report

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Springer Nature presents a custom webcast on: Nutrition and brain health

Date: Thursday December 1, 2016

Register for the webcast and live Q&A session

Sponsored by:
Focus on Psychiatric Disorders

Compared to other areas, psychiatric research faces unique biological, technological, clinical, regulatory and ethical challenges.

In this focus Nature Neuroscience and Nature Medicine present a collection of Commentaries, Perspectives, and Reviews that address these challenges.

Access the Focus online

Produced with support of a grant from: 
Avanir Pharmaceuticals, Inc.

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.

Access the Outlook free online



Viewpoints: an interactive forum for debates and discussions   p1537
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.

News and Views


Rare mutations and educational attainment   pp1538 - 1539
David Cesarini
Intellectual disabilities and associated neurodevelopmental disorders may result from rare genetic mutations. Ganna et al. show that these also help explain variability in educational attainment, a proxy for cognitive function.

See also: Brief Communication by Ganna et al.

Astrocyte endfeet march to the beat of different vessels   pp1539 - 1541
Ravi L Rungta and Serge Charpak
During synaptic activation, the function of astrocyte endfeet depends on the vascular target: at the capillary, but not at the arteriole, a newly described P2X1R-phospholipase D2 pathway modulates prostaglandin E2 release and vessel dilation.

See also: Article by Mishra et al.

Many paths from state to state   pp1541 - 1542
Matthew T Kaufman and Anne K Churchland
Humans and animals can collect and maintain information that guides decisions, but how neural circuits achieve this is unknown. It seems neural populations may do so by passing through diverse states in many possible sequences.

See also: Article by Morcos & Harvey

The slippery slope of dishonesty   pp1543 - 1544
Jan B Engelmann and Ernst Fehr
Recent experiments suggest that dishonesty can escalate from small levels to ever-larger ones along a 'slippery slope'. Activity in bilateral amygdala tracks this gradual adaptation to repeated acts of self-serving dishonesty.

See also: Article by Garrett et al.

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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.
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.



Functional and structural underpinnings of neuronal assembly formation in learning   pp1553 - 1562
Anthony Holtmaat and Pico Caroni
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.

Brief Communications


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.
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

Gravity orientation tuning in macaque anterior thalamus   pp1566 - 1568
Jean Laurens, Byounghoon Kim, J David Dickman and Dora E Angelaki
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.

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



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.
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.

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.
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.

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.
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.

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.
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.

C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons   pp1610 - 1618
Rajeeve Sivadasan, Daniel Hornburg, Carsten Drepper, Nicolas Frank, Sibylle Jablonka et al.
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.

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.
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

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.
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.

Antagonistic negative and positive neurons of the basolateral amygdala   pp1636 - 1646
Joshua Kim, Michele Pignatelli, Sangyu Xu, Shigeyoshi Itohara and Susumu Tonegawa
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.

Layer 4 fast-spiking interneurons filter thalamocortical signals during active somatosensation   pp1647 - 1657
Jianing Yu, Diego A Gutnisky, S Andrew Hires and Karel Svoboda
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.

Experience-dependent spatial expectations in mouse visual cortex   pp1658 - 1664
Aris Fiser, David Mahringer, Hassana K Oyibo, Anders V Petersen, Marcus Leinweber et al.
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.

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.
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.

History-dependent variability in population dynamics during evidence accumulation in cortex   pp1672 - 1681
Ari S Morcos and Christopher D Harvey
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.

Neural substrate of dynamic Bayesian inference in the cerebral cortex   pp1682 - 1689
Akihiro Funamizu, Bernd Kuhn and Kenji Doya
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.

Synaptic scaling rule preserves excitatory-inhibitory balance and salient neuronal network dynamics   pp1690 - 1696
Jérémie Barral and Alex D Reyes
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.

Computational principles of synaptic memory consolidation   pp1697 - 1706
Marcus K Benna and Stefano Fusi
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.

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.
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.

Activity flow over resting-state networks shapes cognitive task activations   pp1718 - 1726
Michael W Cole, Takuya Ito, Danielle S Bassett and Douglas H Schultz
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.

The brain adapts to dishonesty   pp1727 - 1732
Neil Garrett, Stephanie C Lazzaro, Dan Ariely and Tali Sharot
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

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



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.
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.

Technical Report


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.
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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