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|  |  | TABLE OF CONTENTS
| December 2012 Volume 15, Issue 12 |  |  |  |  | News and Views
Review
Brief Communications
Articles
Technical Reports
| |  | |  |  | Advertisement |  | |  | | Advertisement |  | |  | | News and Views | Top |  |  |  | |  | Review | Top |  |  |  | Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders pp1613 - 1620 Mazen A Kheirbek, Kristen C Klemenhagen, Amar Sahay and René Hen doi:10.1038/nn.3262 In this review, the authors examine the link between adult hippocampal neurogenesis and anxiety and depression. They propose that impaired pattern separation underlies the overgeneralization often seen in anxiety disorders.
|  | Brief Communications | Top |  |  |  | Impaired adult myelination in the prefrontal cortex of socially isolated mice pp1621 - 1623 Jia Liu, Karen Dietz, Jacqueline M DeLoyht, Xiomara Pedre, Dipti Kelkar, Jasbir Kaur, Vincent Vialou, Mary Kay Lobo, David M Dietz, Eric J Nestler, Jeffrey Dupree and Patrizia Casaccia doi:10.1038/nn.3263 In this study, the authors show that subjecting adult animals to prolonged social isolation results in impaired heterochromatin formation in oligodendrocytes and decreased myelin thickness, specifically in the prefrontal cortex. This suggests that social experience can regulate myelin plasticity in the adult via an epigenetic program.
|  |  |  | Subcellular connectivity underlies pathway-specific signaling in the nucleus accumbens pp1624 - 1626 Andrew F MacAskill, Justin P Little, John M Cassel and Adam G Carter doi:10.1038/nn.3254 The authors report that medium spiny neurons in the mouse nucleus accumbens receive inputs from the cortex, thalamus and hippocampus, but the differential subcellular connectivity of hippocampal inputs makes them much weaker onto neurons in the indirect pathway.
|  | Articles | Top |  |  |  | BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets pp1627 - 1635 Luca Tiberi, Jelle van den Ameele, Jordane Dimidschstein, Julie Piccirilli, David Gall, Adèle Herpoel, Angéline Bilheu, Jerome Bonnefont, Michelina Iacovino, Michael Kyba, Tristan Bouschet and Pierre Vanderhaeghen doi:10.1038/nn.3264 The authors show that the oncogene Bcl6 is necessary for proper cortical neurogenesis in vivo and from embryonic stem cells. BCL6 alters the composition of Notch-dependent transcriptional complexes at the Hes5 promoter, including the recruitment of Sirt1, to promote transition to a neurogenic fate despite active Notch signaling.
|  |  |  | Sustained Hox5 gene activity is required for respiratory motor neuron development pp1636 - 1644 Polyxeni Philippidou, Carolyn M Walsh, Josée Aubin, Lucie Jeannotte and Jeremy S Dasen doi:10.1038/nn.3242 In this study, the authors show that Hox5 genes are essential for the organization, survival and axonal branching of motor neurons required for breathing. Unexpectedly, this requirement for Hox5 activity persists to later developmental stages.
See also: News and Views by Castellani & Kania
|  |  |  | A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development pp1645 - 1654 Michael J Soskis, Hsin-Yi Henry Ho, Brenda L Bloodgood, Michael A Robichaux, Athar N Malik, Bulent Ataman, Alex A Rubin, Janine Zieg, Chao Zhang, Kevan M Shokat, Nikhil Sharma, Christopher W Cowan and Michael E Greenberg doi:10.1038/nn.3249 The EphB family of receptor tyrosine kinases can signal bidirectionally and functions in a kinase-dependent and kinase-independent manner. To determine the importance of the kinase activity of EphBs for axonal guidance and synaptogenesis, the authors used a chemical genetic method and generated knock-in mice that allow the kinase activity of EphBs to be inhibited without altering kinase-independent functions of EphBs. They find that specific inhibition of EphB kinase activity had no effect on synaptogenesis, but impaired axonal guidance, thereby implicating the kinase function of EphB in one neuronal process, but not other processes that are nevertheless dependent on EphBs.
|  |  |  | GKAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling pp1655 - 1666 Seung Min Shin, Nanyan Zhang, Jonathan Hansen, Nashaat Z Gerges, Daniel T S Pak, Morgan Sheng and Sang H Lee doi:10.1038/nn.3259 Ubiquitin proteasome system-mediated, neuronal activity-dependent protein turnover at synapses often occurs in an ensemble fashion where a group or groups of postsynaptic density (PSD) proteins are degraded together in a homeostatic response. This study shows that the synaptic level of the PSD scaffolding protein called GKAP (also known as SAPAP1) is bidirectionally regulated in a homeostatic fashion and is mediated by differential phosphorylation by CaM kinase II isoforms.
|  |  |  | Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number pp1667 - 1674 Hyung-Bae Kwon, Yevgenia Kozorovitskiy, Won-Jong Oh, Rui T Peixoto, Nazia Akhtar, Jessica L Saulnier, Chenghua Gu and Bernardo L Sabatini doi:10.1038/nn.3256 The function of neuroligins in regulating synapse formation remains controversial. Here, the authors show that neuroligin-1 (NL1) regulates activity-dependent synaptogenesis and mature synapse number on cortical layer 2/3 pyramidal neurons in vivo. They find that relative differences in transcellular expression of NL1, rather than absolute expression levels, regulate synapse number.
See also: News and Views by Barrow & McAllister
|  |  |  | PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans pp1675 - 7682 Arantza Barrios, Rajarshi Ghosh, Chunhui Fang, Scott W Emmons and Maureen M Barr doi:10.1038/nn.3253 In worms, male exploratory behavior is influenced by two competing needs, food and sex. In this paper, the authors highlight the importance of the pigment dispersing factor signaling pathway in the normal function of a gender-shared neuronal circuit that is involved male-specific reproductive drive.
|  |  |  | Orthogonal micro-organization of orientation and spatial frequency in primate primary visual cortex pp1683 - 1690 Ian Nauhaus, Kristina J Nielsen, Anita A Disney and Edward M Callaway doi:10.1038/nn.3255 In this study, the authors used two-photon imaging in macaque monkey to show that orientation and spatial frequency maps are intimately related at a fine spatial scale. They find that the map gradients have a striking tendency toward orthogonality and co-vary negatively from cell to cell at the spatial scale of cortical columns.
|  |  |  | Correlated input reveals coexisting coding schemes in a sensory cortex pp1691 - 1699 Luc Estebanez, Sami El Boustani, Alain Destexhe and Daniel E Shulz doi:10.1038/nn.3258 Here the authors investigate the neural basis of coherence and contrast detection in the somatosensory system. Model-based analysis of the responses of neurons in the barrel cortex reveal different coding schemes according to the level of correlation in the spatiotemporal patterns of whisker stimulation. The cell populations they find in the primary somatosensory cortex are analogous to cell classes previously reported in two separate cortical areas of the visual system.
|  |  |  | Optical controlling reveals time-dependent roles for adult-born dentate granule cells pp1700 - 1706 Yan Gu, Maithe Arruda-Carvalho, Jia Wang, Stephen R Janoschka, Sheena A Josselyn, Paul W Frankland and Shaoyu Ge doi:10.1038/nn.3260 Newly generated dentate granule cells in the hippocampus at 4 weeks after their 'birth' are more plastic than existing neurons. The authors use a combined retroviral and optogenetic approach to show that silencing these 4-week-old cells, but not cells of other ages, impaired retrieval of hippocampal memory.
See also: News and Views by Schoenfeld & Gould
|  |  |  | Glucocorticoid receptors recruit the CaMKIIα-BDNF-CREB pathways to mediate memory consolidation pp1707 - 1714 Dillon Y Chen, Dhananjay Bambah-Mukku, Gabriella Pollonini and Cristina M Alberini doi:10.1038/nn.3266 The positive effect of stress on memory formation involves glucocorticoid receptors, but is otherwise not well understood. This article reports that stressful memory consolidation in rats involves the activation of a nongenomic molecular cascade downstream of hippocampal glucocorticoid receptors that overlaps with the BDNF-TrkB signaling pathway.
|  |  |  | Neural population partitioning and a concurrent brain-machine interface for sequential motor function pp1715 - 1722 Maryam M Shanechi, Rollin C Hu, Marissa Powers, Gregory W Wornell, Emery N Brown and Ziv M Williams doi:10.1038/nn.3250 Brain-machine interfaces (BMIs) have typically focused on performing single-targeted movements. Here the authors report the presence of two subpopulations of neurons in the monkey premotor cortex that allow two planned targets to be simultaneously held in working memory without degradation. They use this finding to develop a BMI that concurrently decodes a full motor sequence in advance of movement and then accurately executes it.
|  |  |  | Diverse types of genetic variation converge on functional gene networks involved in schizophrenia pp1723 - 1728 Sarah R Gilman, Jonathan Chang, Bin Xu, Tejdeep S Bawa, Joseph A Gogos, Maria Karayiorgou and Dennis Vitkup doi:10.1038/nn.3261 The authors use a computational approach (NETBAG+) to integrate and analyze diverse genetic data and apply this to study schizophrenia-associated genetic variations. They identify gene networks related to axon guidance, synaptic function, cell mobility and chromosomal remodeling.
|  |  |  | A supramodal accumulation-to-bound signal that determines perceptual decisions in humans pp1729 - 1735 Redmond G O'Connell, Paul M Dockree and Simon P Kelly doi:10.1038/nn.3248 This study uses EEG in humans to isolate and track an evolving, domain-general decision signal, which varies with accumulated evidence, but is independent of overt actions.
|  |  |  | Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence pp1736 - 1741 Cory A Burghy, Diane E Stodola, Paula L Ruttle, Erin K Molloy, Jeffrey M Armstrong, Jonathan A Oler, Michelle E Fox, Andrea S Hayes, Ned H Kalin, Marilyn J Essex, Richard J Davidson and Rasmus M Birn doi:10.1038/nn.3257 The authors assessed the contributions of early life stress (ELS) and childhood cortisol levels to adolescent resting-state functional connectivity. In females, ELS predicted increased cortisol levels in childhood, which predicted decreased amygdala-ventromedial prefrontal cortex (vmPFC) functional connectivity. Amygdala-vmPFC connectivity was inversely correlated with anxious sympotms and positively correlated with depressive symptoms.
See also: News and Views by Bogdan & Hariri
|  | Technical Reports | Top |  |  |  | Fluorescent and photo-oxidizing TimeSTAMP tags track protein fates in light and electron microscopy pp1742 - 1751 Margaret T Butko, Jin Yang, Yang Geng, Hyung Joon Kim, Noo Li Jeon, Xiaokun Shu, Mason R Mackey, Mark H Ellisman, Roger Y Tsien and Michael Z Lin doi:10.1038/nn.3246 Butko and colleagues report the invention of fluorescent and photo-oxidizing versions of a molecular probe named TimeSTAMP that allows temporal tagging of newly synthesized proteins of interest. The study uses these new tools to track basal and pharmacologically-induced synthesis of the synaptic protein PDS-95 in real time via live fluorescent imaging and/or with ultrastructural resolution using electron microscopy.
|  |  |  | A high-performance neural prosthesis enabled by control algorithm design pp1752 - 1757 Vikash Gilja, Paul Nuyujukian, Cindy A Chestek, John P Cunningham, Byron M Yu, Joline M Fan, Mark M Churchland, Matthew T Kaufman, Jonathan C Kao, Stephen I Ryu and Krishna V Shenoy doi:10.1038/nn.3265 Current neural prostheses can translate neural activity into control signals for guiding prosthetic devices, but poor performance limits practical application. Here the authors present a new cursor-control algorithm that approaches native arm control speed and accuracy, permits sustained uninterrupted use for hours, generalizes to more challenging tasks and provides repeatable high performance for years after implantation, thereby increasing the clinical viability of neural prostheses.
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