Nature Neuroscience Contents: November 2013 Volume 16 Number 11, pp 1509 - 1708

Advertisement Prospective Psychology: A Project of the University of Pennsylvania and the John Templeton Foundation. Templeton Science of Prospection Awards. Request for Applications - Deadline: January 1, 2014.  Click for more information. TABLE OF CONTENTS November 2013 Volume 16, Issue 11 Editorial News and Views Reviews Brief Communications Articles Advertisement   Pharmacology, physiology and regulation of tonic GABAA conductances (open access) Topic Editors: Matthew Walker, Istvan Mody and Alexey Semyanov Submission deadline: 01 Aug 2014 Frontiers in Neural Circuits GABAA receptors mediate two forms of signaling in the brain: phasic and tonic. Phasic signaling is mediated by synaptic GABAA receptors, while tonic signaling is mediated by extrasynaptic GABAA receptors.  Find out how you can contribute to this Research Topic or even host your own. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Medicine and Eli Lilly and Company present: Shifting Paradigms on Alzheimer's Disease December 3, 2013 Lilly Corporate Center, Indianapolis, IN, USA  Click here to register for this symposium today!   Editorial Top Unconventional gene regulation in the CNS   p1509 doi:10.1038/nn.3571 Dysregulation of protein translation and RNA processing mechanisms in the brain can result in subtle, but widespread, neurological disorders. A collection of Review and Perspective articles in this issue of Nature Neuroscience highlights some of the more unconventional mechanisms of post-transcriptional modifications in the CNS. News and Views Top Sleep aromatherapy curbs conditioned fear   pp1510 - 1512 John T Wixted doi:10.1038/nn.3556 We know that humans are capable of learning during sleep. Research now shows that they are also capable of unlearning during sleep, and in a way that alters the neural representation of a feared stimulus: re-exposure to an odor during slow-wave sleep promotes extinction of an aversive visual association learned in that odor context. See also: Brief Communication by Hauner et al. Best-laid schemes for interneuron origin of mice and men   pp1512 - 1514 Zoltán Molnár and Simon J B Butt doi:10.1038/nn.3557 Two studies emphasize similarities in the developmental origin of cortical interneurons across mammals. They suggest that most interneurons in humans and macaques have a subcortical origin. See also: Article by Hansen et al. | Article by Ma et al. Adolescent dopamine slows spine maturation   pp1514 - 1516 Dong-Min Yin, Wen-Cheng Xiong and Lin Mei doi:10.1038/nn.3558 A study now identifies an unexpected function of the D2 dopamine receptor in synapse maturation during a critical period in mice. The findings may have implications for the onset of schizophrenia in humans. See also: Article by Jia et al. One in a thousand: defining the limits of olfactory perception   pp1516 - 1517 Nathan E Schoppa doi:10.1038/nn.3551 Each olfactory sensory neuron in mice is defined by which of the ∼1,000 odorant receptor genes that it expresses. Using optogenetics, a study finds that mice can perceive stimulation of only a single class of olfactory sensory neuron. See also: Article by Smear et al. Neuroscience JOBS of the week Position in Theoretical Neuroscience Princeton University 4-year PhD Programme in Neuroscience University of Sussex Neuroscience Director Virginia Tech Postdoctoral Position in Developmental Neuroscience Children's National Medical Center Systems Neuroscience Tenure Track Assistant Professor Harvard Medical School More Science jobs from Neuroscience EVENT Applied Neuroscience 2014 30th January 2014 - 2nd February 2014 Utrecht, Netherlands More science events from Reviews Top Deciphering the functions and regulation of brain-enriched A-to-I RNA editing   pp1518 - 1522 Jin Billy Li and George M Church doi:10.1038/nn.3539 Brain enriched RNA editing of Adenosine-to-Inosine (A-to-I) increases the amount of information encoded in the genome and diversifies the transcriptome. Here the authors discuss how recent technological and analytical developments may facilitate the discovery of RNA editing sites and the understanding of their functions and regulation. Maintaining genome stability in the nervous system   pp1523 - 1529 Peter J McKinnon doi:10.1038/nn.3537 This review article by Peter McKinnon discusses the latest progress in understanding the complexity of DNA damage and related repair pathways in the nervous system. The piece highlights DNA damage/repair in both normal course of brain development and in aging, and discusses possible dysfunction of this mechanism in disease as uniquely faced by postmitotic neurons in the brain. The translation of translational control by FMRP: therapeutic targets for FXS   pp1530 - 1536 Jennifer C Darnell and Eric Klann doi:10.1038/nn.3379 In this review, the authors discuss the function of fragile X mental retardation protein (FMRP) in regulating the synthesis of plasticity-related target proteins. The authors review the known mRNA targets of FMRP and discuss the potential therapeutic implications of this research. mTOR complexes in neurodevelopmental and neuropsychiatric disorders   pp1537 - 1543 Mauro Costa-Mattioli and Lisa M Monteggia doi:10.1038/nn.3546 Mechanistic target of rapamycin (mTOR) integrates a variety of inputs and regulates diverse cellular functions. In this review, the authors discuss recent studies implicating mTOR signaling in neurodevelopmental and psychiatric diseases, and the mechanisms that may underlie these effects. Emerging roles for post-transcriptional regulation in circadian clocks   pp1544 - 1550 Chunghun Lim and Ravi Allada doi:10.1038/nn.3543 Here the authors review emerging evidence from circadian systems, indicating an important role for post-transcriptional regulation, from splicing, polyadenylation and mRNA stability to translation and noncoding functions exemplified by microRNAs. They hypothesize that post-transcriptional control confers to circadian clocks enhanced robustness as well as the ability to adapt to different environments. Brief Communications Top Category-specific integration of homeostatic signals in caudal but not rostral human insula   pp1551 - 1552 W Kyle Simmons, Kristina M Rapuano, Seth J Kallman, John E Ingeholm, Bernard Miller et al. doi:10.1038/nn.3535 It has been suggested that posterior insular regions code lower-level sensory information and anterior regions code higher-level stimulus significance relative to the body's homeostatic needs. However, here the authors report that the caudal, but not rostral, insula response to food images was directly related to the body's homeostatic state. Stimulus-specific enhancement of fear extinction during slow-wave sleep   pp1553 - 1555 Katherina K Hauner, James D Howard, Christina Zelano and Jay A Gottfried doi:10.1038/nn.3527 Sleep has been shown to strengthen various types of memory, including emotional memory. Here the authors show that in subjects who have learned to associate an odor with an electric shock, re-exposure to the odor during slow-wave sleep promotes extinction of the memory for the odor-shock association. See also: News and Views by Wixted Advertisement Precellys® tissue homogenizer, the clever solution for efficient brain homogenization! Expert in Life Sciences, Bertin Technologies manufactures the Precellys® products range dedicated to grinding, lysing and homogenization of biological samples. Precellys® is the only brand offering an efficient cooling option, Cryolys. With dry-ice or liquid nitrogen, get your samples at optimal temperature before, during and after homogenization with the Online Application Center with hundreds of publications, application notes and protocols for brain samples. Find us at Neuroscience 2013, booth #3410, and get a live demo!   Articles Top TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding   pp1556 - 1566 Mayumi Okamoto, Takashi Namba, Tomoyasu Shinoda, Takefumi Kondo, Tadashi Watanabe et al. doi:10.1038/nn.3525 The authors show that shortening of the basal process in neural progenitor cells by depletion of TAG-1 results in overcrowding in the periventricular space and, eventually, delamination and aberrant migration. These results suggest that one of the functions of interkinetic nuclear migration is to prevent progenitor congestion and mechanical stress. Transcriptional repression of Bmp2 by p21Waf1/Cip1 links quiescence to neural stem cell maintenance   pp1567 - 1575 Eva Porlan, José Manuel Morante-Redolat, María Ángeles Marqués-Torrejón, Celia Andreu-Agulló, Carmen Carneiro et al. doi:10.1038/nn.3545 The self renewal and long-term maintenance of neural stem cells (NSCs) is related to how quickly they pass through the cell cycle. Here the authors describe a new role for the cyclin-dependent kinase inhibitor p21 and show that it maintains an active NSC pool through repression of Bmp2. Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences   pp1576 - 1587 David V Hansen, Jan H Lui, Pierre Flandin, Kazuaki Yoshikawa, John L Rubenstein et al. doi:10.1038/nn.3541 GABAergic cortical interneurons have important roles in the computations of neural circuits, but their developmental origin in primates is controversial. Here the authors characterize neural stem cell and progenitor cell organization in the developing human ganglionic eminences and reveal that, just as in rodents, they give rise to a majority of cortical GABAergic neurons. See also: Article by Ma et al. | News and Views by Molnar & Butt Subcortical origins of human and monkey neocortical interneurons   pp1588 - 1597 Tong Ma, Congmin Wang, Lei Wang, Xing Zhou, Miao Tian et al. doi:10.1038/nn.3536 In primates, the developmental origin of neocortical interneurons is controversial. Here the authors map out expression patterns of key transcription factors in the developing human and monkey brain and reveal that, just as in rodents, the majority of cortical GABAergic neurons originate from the ganglionic eminences. See also: Article by Hansen et al. | News and Views by Molnar & Butt Dual origins of functionally distinct O-LM interneurons revealed by differential 5-HT3AR expression   pp1598 - 1607 Ramesh Chittajallu, Michael T Craig, Ashley McFarland, Xiaoqing Yuan, Scott Gerfen et al. doi:10.1038/nn.3538 There is a diverse set of cortical interneurons that uniquely participate in the computations of large cell assemblies. Here the authors show that the same type of interneuron within the hippocampus, those projecting to the oriens-lacunosum moleculare, can have distinct developmental origins and different circuit functions. Neuroprotection and lifespan extension in Ppt1-/- mice by NtBuHA: therapeutic implications for INCL   pp1608 - 1617 Chinmoy Sarkar, Goutam Chandra, Shiyong Peng, Zhongjian Zhang, Aiyi Liu et al. doi:10.1038/nn.3526 There is currently no effective treatment for infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease that occurs in childhood. Here the authors show that a small molecule thioesterase-mimetic can alleviate neuropathology and extend lifespan in an animal model of the disease. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation   pp1618 - 1626 Tobias Goldmann, Peter Wieghofer, Philippe F Müller, Yochai Wolf, Diana Varol et al. doi:10.1038/nn.3531 In this study, the authors generate a new mouse model that allows selective genetic targeting of microglial cells. Using this model, they show that elimination of TGF-β-activated kinase 1 (TAK1) specifically in microglial cells reduces pathology in a mouse model of multiple sclerosis by inhibiting NF-κB, ERK and JNK signaling pathways. Age-dependent regulation of synaptic connections by dopamine D2 receptors   pp1627 - 1636 Jie-Min Jia, Jun Zhao, Zhonghua Hu, Daniel Lindberg and Zheng Li doi:10.1038/nn.3542 The authors show that type 2 dopamine receptors (D2Rs) negatively regulate spine morphogenesis in the hippocampi of adolescent mice. Spine deficiency resulting from D2R overactivation was associated with dysconnectivity in the entorhinal-hippocampal circuit and working memory deficits. These phenotypes could be rescued by D2R antagonists given during adolescence. See also: News and Views by Yin et al. Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus   pp1637 - 1643 Sonia Jego, Stephen D Glasgow, Carolina Gutierrez Herrera, Mats Ekstrand, Sean J Reed et al. doi:10.1038/nn.3522 The authors find that optogenetic stimulation of melanin-concentrating hormone (MCH)-expressing neurons in the lateral hypothalamus selectively extends the duration of paradoxical sleep episodes in mice. Activation of MCH fibers in the tuberomammillary nucleus leads to the release of GABA and a similar increase in paradoxical sleep stability. Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving   pp1644 - 1651 Brian R Lee, Yao-Ying Ma, Yanhua H Huang, Xiusong Wang, Mami Otaka et al. doi:10.1038/nn.3533 In rats self-administering cocaine, drug seeking behavior induced by a cocaine-paired cue increases progressively during cocaine withdrawal. The authors detected silent synapses in basolateral amygdala-to-nucleus accumbens projections during early withdrawal, but these synapses progressively disappeared during protracted withdrawal. Optogenetic 're-silencing' of these synapses decreased cue-induced cocaine seeking following withdrawal. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid   pp1652 - 1661 Zuzana Justinova, Paola Mascia, Hui-Qiu Wu, Maria E Secci, Godfrey H Redhi et al. doi:10.1038/nn.3540 α7-nicotinic acetylcholine receptors (α7nAChRs) modulate the effects of the main psychoactive ingredient of marijuana, Δ9-tetrahydrocannabinol (THC), in the brain. Here the authors show that pharmacologically enhancing kynurenic acid, an endogenous modulator of α7nAChRs, attenuated the rewarding properties of THC and prevented drug relapse in monkeys and rats. A disinhibitory circuit mediates motor integration in the somatosensory cortex   pp1662 - 1670 Soohyun Lee, Illya Kruglikov, Z Josh Huang, Gord Fishell and Bernardo Rudy doi:10.1038/nn.3544 The authors find that long-range axons from primary motor cortex (vM1) preferentially recruit vasointestinal peptide (VIP)-expressing interneurons in somatosensory cortex (S1). VIP neurons in turn inhibit somatostatin-expressing interneurons that target the distal dendrites of pyramidal cells in S1. This dis-inhibitory circuit is active during voluntary movement, suggesting that it participates in the modulation of primary cortical sensory processing by motor cortex. Membrane potential correlates of sensory perception in mouse barrel cortex   pp1671 - 1677 Shankar Sachidhanandam, Varun Sreenivasan, Alexandros Kyriakatos, Yves Kremer and Carl C H Petersen doi:10.1038/nn.3532 Here the authors demonstrate a causal role for the barrel cortex in the detection of single whisker stimuli. Whisker deflection evoked an early (<50 ms) reliable sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced in hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Equalization of odor representations by a network of electrically coupled inhibitory interneurons   pp1678 - 1686 Peixin Zhu, Thomas Frank and Rainer W Friedrich doi:10.1038/nn.3528 Using optogenetics and other methods in the zebrafish olfactory bulb, the authors explore the role of interneurons that are densely connected to mitral cells (MCs) by both electrical and chemical synapses. These interneurons maintain the mean and distribution of MC population activity within narrow limits as stimulus intensity changes. Multiple perceptible signals from a single olfactory glomerulus   pp1687 - 1691 Matthew Smear, Admir Resulaj, Jingji Zhang, Thomas Bozza and Dmitry Rinberg doi:10.1038/nn.3519 The authors use optogenetics to selectively activate single glomeruli in behaving mice. They find that mice can perceive the stimulation of a single glomerulus, even on an intense odor background. Different input intensities and the timing of input relative to sniffing can also be discriminated. This suggests that each glomerulus can transmit odor information using identity, intensity and temporal coding cues. See also: News and Views by Schoppa Origin and effect of phototransduction noise in primate cone photoreceptors   pp1692 - 1700 Juan M Angueyra and Fred Rieke doi:10.1038/nn.3534 The origin and functional importance of noise in mammalian cones is poorly understood. Here, the authors find that channel noise and fluctuations in cGMP dominate cone noise, that adaptation in cones affects signal and noise differently, and that cones generate less noise than previously thought. These results help reconcile cone noise and behavioral sensitivity. Computation of linear acceleration through an internal model in the macaque cerebellum   pp1701 - 1708 Jean Laurens, Hui Meng and Dora E Angelaki doi:10.1038/nn.3530 In this study, the authors recorded from the cerebellum while monkeys experienced an illusory perception of self-motion, and found that the neurons encoded the erroneous linear acceleration. Their findings provide evidence that the cerebellum might be involved in the implementation of internal models, as previously hypothesized by theorists. 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