Nature Neuroscience Contents: August 2013 Volume 16 Number 8, pp 983 - 1161

TABLE OF CONTENTS August 2013 Volume 16, Issue 8 Editorial News and Views Brief Communications Articles Technical Report Advertisement Laserglow Technologies: DPSS & Diode Laser Systems For use with optogenetics and most common fluorophores. Over 60 wavelengths available from 266 nm to 2200 nm, with custom options like fiber coupling, various modulation signal inputs, low optical noise, and more. Find out why leading neuroscience labs choose Laserglow for their light source solutions:  www.laserglow.com Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Neuroscience FOCUS ON NEUROTECHNIQUES The rapid pace of technological innovation has opened up many new avenues for exploring the brain. This special issue focuses on recent advances in methods and techniques that are pushing the frontiers of neuroscience. Read this Focus online: www.nature.com/neuro/focus/neurotechniques   Editorial Top Back to basics   p983 doi:10.1038/nn.3483 Successful translational research requires a solid understanding of the systems involved and their normal functions, which only basic research is equipped to provide. News and Views Top Behavioral control by the orbital prefrontal cortex: reversal of fortune   pp984 - 985 Mark G Baxter and Paula L Croxson doi:10.1038/nn.3472 A study shows that selective lesions of the orbital prefrontal cortex in macaques spare behavioral flexibility and emotional processing but impair a test of outcome expectation, suggesting that some psychiatric disorders ascribed to a disrupted orbital prefrontal cortex may instead be caused by more widespread dysfunction. See also: Article by Rudebeck et al. Making antisense of pain   pp986 - 987 Tina W Han and Lily Yeh Jan doi:10.1038/nn.3475 A study now identifies a long noncoding antisense RNA that contributes to neuropathic pain through the suppression of potassium channel expression. See also: Article by Zhao et al. Drinking through the pain   pp987 - 988 Thomas L Kash and John C Crabbe doi:10.1038/nn.3476 A feature of abusive alcohol drinking has been modeled successfully in experiments with rats. The experiments show that changes in NMDA signaling in specific neural circuits accompany the transition to aversion-resistant drinking. See also: Article by Seif et al. Brain-wide gain modulation: the rich get richer   pp989 - 990 Tobias H Donner and Sander Nieuwenhuis doi:10.1038/nn.3471 A study now shows how brain-wide gain modulation, indexed by pupil diameter, shapes the structure of brain-wide neural interactions and, consequently, trial-and-error learning. See also: Article by Eldar et al. Neuroscience JOBS of the week Postdoctoral / Rresearch Associate Position in Auditory Neuroscience Reseaerch Wayne State Univeristy School of Medicine Postdoc Neuroscience Charité-Universitaetsmedizin Berlin/ NeuroCure Clinical Research Center/ Cognitive Neurology Assistant Professor in Developmental Neuroscience, Department of Psychology University of Calgary Associate Professor in Neuroscience / Neuroanatomy University of Fribourg Professor of Systems Neuroscience Professor of Neurogenetics ETH More Science jobs from Neuroscience EVENT Champalimaud Neuroscience Symposium 25.09.13 Lisbon, Portugal More science events from Brief Communications Top Information for decision-making and stimulus identification is multiplexed in sensory cortex   pp991 - 993 David H Gire, Jennifer D Whitesell, Wilder Doucette and Diego Restrepo doi:10.1038/nn.3432 In this study, the authors show that information regarding both the identity and the value of a given odor is multiplexed in the anterior piriform cortex. Specifically, they find that value is encoded by changes in firing rate while identity is determined by sniff-locked spiking. Bidirectional effects of aversive learning on perceptual acuity are mediated by the sensory cortex   pp994 - 996 Mark Aizenberg and Maria Neimark Geffen doi:10.1038/nn.3443 It's unclear how the brain alters sensory processing in response to emotionally laden stimuli. Here the authors show that changes in auditory acuity depend on the auditory cortex and on how specific a cue is in predicting an aversive stimulus. Goal-dependent dissociation of visual and prefrontal cortices during working memory   pp997 - 999 Sue-Hyun Lee, Dwight J Kravitz and Chris I Baker doi:10.1038/nn.3452 The authors report that, when subjects are asked to remember visual properties of an object, object identity can be decoded from fMRI measures of activity in extrastriate, but not prefrontal, cortex, whereas the opposite holds when they are asked to remember nonvisual properties. Thus, the ability to maintain information during working memory is a general and flexible cortical property. Articles Top Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation   pp1000 - 1007 Holden Higginbotham, Jiami Guo, Yukako Yokota, Nicole L Umberger, Chen-Ying Su et al. doi:10.1038/nn.3451 Joubert syndrome, a recessive neurodevelopmental disorder associated with cortical malformations and autism-like features, has been linked to mutations in the gene encoding Arl13b, a cilia-enriched small GTPase. Here, Higginbotham and colleagues show that the early loss of function of Arl13b in mouse cortical progenitors leads to deficits in progenitors' ciliary signaling, apical-basal inversion of the radial glial scaffold and neuronal misplacement. SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons   pp1008 - 1015 Matthew M Dobbin, Ram Madabhushi, Ling Pan, Yue Chen, Dohoon Kim et al. doi:10.1038/nn.3460 Examining the molecular mechanism behind neuronal genomic stability, Dobbin et al. show that the histone lysine deacetylases HDAC1 and SIRT1 are recruited to the sites of DNA double-strand breaks in neurons and demonstrate the importance of HDAC1-SIRT1 functional interactions in DNA double strand-break repairs. The authors also show that pharmacological activation of SIRT1 can stimulate HDAC1 activity and confer neuroprotection after DNA damage in cultured neurons and in two mouse models of neurodegeneration. Developmental origins of central norepinephrine neuron diversity   pp1016 - 1023 Sabrina D Robertson, Nicholas W Plummer, Jacqueline de Marchena and Patricia Jensen doi:10.1038/nn.3458 The authors study the lineal origins of norepinephrine (NE) neurons in the mouse hindbrain. They identify four genetically separable subpopulations of NE neurons, each with distinct anatomical location, axonal morphology and pattern of efferent projections. One unexpected finding is a projection to the prefrontal cortex that originates from outside the locus coeruleus. A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons   pp1024 - 1031 Xiuli Zhao, Zongxiang Tang, Hongkang Zhang, Fidelis E Atianjoh, Jian-Yuan Zhao et al. doi:10.1038/nn.3438 Zhao and colleagues find that neuropathic pain is accompanied by an increase in the expression of an antisense long noncoding RNA (lncRNA) that downregulates Kcna2 currents and increases excitability in rat dorsal root ganglion neurons. Preventing the expression of the so-called Kcna2 antisense RNA mitigates neuropathic pain symptoms. See also: News and Views by Han & Jan Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity   pp1032 - 1041 Jose A Matta, Kenneth A Pelkey, Michael T Craig, Ramesh Chittajallu, Brian W Jeffries et al. doi:10.1038/nn.3459 In this study, the authors show that MGE- and CGE-derived GABAergic interneurons exhibit differences in their synaptic receptor composition. In particular, they find that MGE-derived interneuron synapses are dominated by calcium-permeable, GluA2-lacking AMPARs, whereas CGE-derived interneurons use both NMDARs and GluA2-containing AMPARs. The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry   pp1042 - 1048 Martin E Hess, Simon Hess, Kate D Meyer, Linda A W Verhagen, Linda Koch et al. doi:10.1038/nn.3449 Previous studies have shown genome-wide associations between polymorphisms in the gene FTO (fat mass and obesity associated) and type 2 diabetes and obesity, and genetic manipulation of Fto in mice causes feeding dysregulation and body weight changes. Here Hess et al. show that FTO affects the activity and function of midbrain dopaminergic neurons and subsequent reward-related behaviors. The study also shows that FTO acts as a demethylating enzyme for specific mRNAs in vivo, including mRNAs in the dopaminergic signaling pathway. Bidirectional NMDA receptor plasticity controls CA3 output and heterosynaptic metaplasticity   pp1049 - 1059 David L Hunt, Nagore Puente, Pedro Grandes and Pablo E Castillo doi:10.1038/nn.3461 In this paper, Hunt and colleagues provide the first demonstration of bidirectional plasticity of NMDA receptor-mediated synaptic transmission at the hippocampal mossy fiber to CA3 synapse in rats. They also show that this form of long-term plasticity can influence CA3 burst firing and spike temporal fidelity, and exert bidirectional metaplastic control over plasticity at associational-commissural synapses. Sensory cortex limits cortical maps and drives top-down plasticity in thalamocortical circuits   pp1060 - 1067 Andreas Zembrzycki, Shen-Ju Chou, Ruth Ashery-Padan, Anastassia Stoykova and Dennis D M O'Leary doi:10.1038/nn.3454 Primary somatosensory cortex (S1) contains a map of the body that mirrors maps in hindbrain and thalamus. During development, peripheral changes alter the map in S1. Here the authors use a mouse mutation that alters S1 size and leads to plasticity in the S1 map that is transferred to the thalamic map. Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons   pp1068 - 1076 Carsten K Pfeffer, Mingshan Xue, Miao He, Z Josh Huang and Massimo Scanziani doi:10.1038/nn.3446 Using a combination of optogenetics, single-cell molecular profiling and paired electrophysiological recordings in the mouse visual cortex, Pfeffer and colleagues derived the connectivity matrix of three major classes of interneurons with their post-synaptic GABAergic targets. This study provides a comprehensive overview of the wiring rules of the inhibition of inhibition in the cortex. Specific evidence of low-dimensional continuous attractor dynamics in grid cells   pp1077 - 1084 KiJung Yoon, Michael A Buice, Caswell Barry, Robin Hayman, Neil Burgess et al. doi:10.1038/nn.3450 In this study, the authors show that the spatial responses of populations of grid cells are constrained to a two-dimensional activity manifold, and the relationships between pairs of grid cells are resistant to perturbation. These findings provide evidence of low-dimensional continuous attractor dynamics in the network. Impaired hippocampal rate coding after lesions of the lateral entorhinal cortex   pp1085 - 1093 Li Lu, Jill K Leutgeb, Albert Tsao, Espen J Henriksen, Stefan Leutgeb et al. doi:10.1038/nn.3462 In the hippocampus, coordinates in space are thought to be expressed by the collective firing locations of place cells while the diversity of experience at these locations is encoded by orthogonal variations in firing rates. Here the authors show that these rate variations in CA3 place cells depend on inputs from the lateral entorhinal cortex. Cortical activation of accumbens hyperpolarization-active NMDARs mediates aversion-resistant alcohol intake   pp1094 - 1100 Taban Seif, Shao-Ju Chang, Jeffrey A Simms, Stuart L Gibb, Jahan Dadgar et al. doi:10.1038/nn.3445 The authors show that optogenetic inhibition of inputs from medial prefrontal cortex (mPFC) or insula to the nucleus accumbens core (NAcore) inhibits aversion-resistant alcohol intake. Alcohol-drinking rats showed increased hyperpolarization-active NMDARs at mPFC and insula inputs to NAcore medium spiny neurons. Knocking down these receptors in the NAcore inhibited aversion-resistant alcohol intake. See also: News and Views by Kash & Crabbe GluN2B in corticostriatal circuits governs choice learning and choice shifting   pp1101 - 1110 Jonathan L Brigman, Rachel A Daut, Tara Wright, Ozge Gunduz-Cinar, Carolyn Graybeal et al. doi:10.1038/nn.3457 Corticostriatal NMDARs mediate certain learning and executive functions. Here Brigman et al. demonstrate that the NMDAR GluN2B subunit in dorsolateral striatum of mice is important for learning a behavioral choice and that its action is dissociable from that of GluN2B in orbitofrontal cortex in flexibly shifting choice behavior. Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse   pp1111 - 1117 Segev Barak, Feng Liu, Sami Ben Hamida, Quinn V Yowell, Jeremie Neasta et al. doi:10.1038/nn.3439 The authors show that reconsolidation of alcohol-related memories activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions and systemic or central amygdalar inhibition of mTORC1 during reconsolidation disrupts alcohol-associated memories, leading to a long-lasting suppression of relapse, suggesting a potential therapeutic target to prevent relapse. Canceling actions involves a race between basal ganglia pathways   pp1118 - 1124 Robert Schmidt, Daniel K Leventhal, Nicolas Mallet, Fujun Chen and Joshua D Berke doi:10.1038/nn.3456 Rapid action suppression is often modeled as a race between 'Go' and 'Stop' processes, but how this corresponds to brain mechanisms has been unclear. The authors recorded simultaneously from multiple rat basal ganglia structures during a Stop-signal task and found Go-related activity in striatum and stop-related activity in the subthalamic nucleus. These distinct signals provide convergent, competing influences over individual cells in the substanti anigra pars reticulata, whose activity reflects whether stopping is successful or not. The results tie together neurophysiology and psychological theory to provide a mechanistic account of how we can or cannot cancel forthcoming actions. Attention-dependent reductions in burstiness and action-potential height in macaque area V4   pp1125 - 1131 Emily B Anderson, Jude F Mitchell and John H Reynolds doi:10.1038/nn.3463 This study finds a counterintuitive reduction in neuron bursting during spatial attention. This is explained by a conductance-based model, which also provides a unified explanation for other forms of attentional modulation and correctly predicts the surprising finding that attention decreases action-potential amplitude. Signals in inferotemporal and perirhinal cortex suggest an untangling of visual target information   pp1132 - 1139 Marino Pagan, Luke S Urban, Margot P Wohl and Nicole C Rust doi:10.1038/nn.3433 To investigate how visual input is combined with information about the current task, the authors recorded neural responses in inferotemporal (IT) and perirhinal (PRH) cortex as macaque monkeys performed a match to sample task. Although both areas represented similar amounts of information, extracting the behaviorally relevant information was easier in PRH. Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating   pp1140 - 1145 Peter H Rudebeck, Richard C Saunders, Anna T Prescott, Lily S Chau and Elisabeth A Murray doi:10.1038/nn.3440 Existing data are consistent with a role for the orbitofrontal cortex (OFC) either in regulating emotion and enhancing behavioral flexibility or in updating valuations on the basis of motivational states. Here the authors show that excitotoxic lesions of OFC impair value updating but do not alter either behavioral flexibility or emotion regulation and that previous observations may have been the result of damage to nearby fiber tracts. See also: News and Views by Baxter & Croxson The effects of neural gain on attention and learning   pp1146 - 1153 Eran Eldar, Jonathan D Cohen and Yael Niv doi:10.1038/nn.3428 Here the authors show that measures of pupil diameter, which are thought to track levels of LC-NE activity and neural gain, are correlated with the degree to which learning is focused on stimulus dimensions that individual human participants are more predisposed to process. They further show that the pupillary and behavioral variables are correlated with global changes in the strength and clustering of functional connectivity, as brain-wide fluctuations of gain would predict. See also: News and Views by Donner & Nieuwenhuis Technical Report Top SeeDB: a simple and morphology-preserving optical clearing agent for neuronal circuit reconstruction   pp1154 - 1161 Meng-Tsen Ke, Satoshi Fujimoto and Takeshi Imai doi:10.1038/nn.3447 This technical report describes a method to clear fixed brain tissues while allowing for fluorescent dye tracing and retaining cellular morphology. The authors demonstrate the utility of the technique by obtaining a wiring diagram for sister mitral cells. Top Advertisement Nature Reviews Neuroscience Article Series on Neuroscience and the law This Article Series explores the interaction between neuroscience and the legal system. Read discussions on issues pertaining to criminal responsibility, drug policy, memory and the dissemination of neuroscientific findings in the courtroom. 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