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Nature Neuroscience

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https://www.readbyqxmd.com/read/28628104/active-dendritic-integration-as-a-mechanism-for-robust-and-precise-grid-cell-firing
#1
Christoph Schmidt-Hieber, Gabija Toleikyte, Laurence Aitchison, Arnd Roth, Beverley A Clark, Tiago Branco, Michael Häusser
Understanding how active dendrites are exploited for behaviorally relevant computations is a fundamental challenge in neuroscience. Grid cells in medial entorhinal cortex are an attractive model system for addressing this question, as the computation they perform is clear: they convert synaptic inputs into spatially modulated, periodic firing. Whether active dendrites contribute to the generation of the dual temporal and rate codes characteristic of grid cell output is unknown. We show that dendrites of medial entorhinal cortex neurons are highly excitable and exhibit a supralinear input-output function in vitro, while in vivo recordings reveal membrane potential signatures consistent with recruitment of active dendritic conductances...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28628103/a-common-haplotype-lowers-pu-1-expression-in-myeloid-cells-and-delays-onset-of-alzheimer-s-disease
#2
Kuan-Lin Huang, Edoardo Marcora, Anna A Pimenova, Antonio F Di Narzo, Manav Kapoor, Sheng Chih Jin, Oscar Harari, Sarah Bertelsen, Benjamin P Fairfax, Jake Czajkowski, Vincent Chouraki, Benjamin Grenier-Boley, Céline Bellenguez, Yuetiva Deming, Andrew McKenzie, Towfique Raj, Alan E Renton, John Budde, Albert Smith, Annette Fitzpatrick, Joshua C Bis, Anita DeStefano, Hieab H H Adams, M Arfan Ikram, Sven van der Lee, Jorge L Del-Aguila, Maria Victoria Fernandez, Laura Ibañez, Rebecca Sims, Valentina Escott-Price, Richard Mayeux, Jonathan L Haines, Lindsay A Farrer, Margaret A Pericak-Vance, Jean Charles Lambert, Cornelia van Duijn, Lenore Launer, Sudha Seshadri, Julie Williams, Philippe Amouyel, Gerard D Schellenberg, Bin Zhang, Ingrid Borecki, John S K Kauwe, Carlos Cruchaga, Ke Hao, Alison M Goate
A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28628102/regulation-of-body-weight-and-energy-homeostasis-by-neuronal-cell-adhesion-molecule-1
#3
Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28628101/dynamic-illumination-of-spatially-restricted-or-large-brain-volumes-via-a-single-tapered-optical-fiber
#4
Ferruccio Pisanello, Gil Mandelbaum, Marco Pisanello, Ian A Oldenburg, Leonardo Sileo, Jeffrey E Markowitz, Ralph E Peterson, Andrea Della Patria, Trevor M Haynes, Mohamed S Emara, Barbara Spagnolo, Sandeep Robert Datta, Massimo De Vittorio, Bernardo L Sabatini
Optogenetics promises precise spatiotemporal control of neural processes using light. However, the spatial extent of illumination within the brain is difficult to control and cannot be adjusted using standard fiber optics. We demonstrate that optical fibers with tapered tips can be used to illuminate either spatially restricted or large brain volumes. Remotely adjusting the light input angle to the fiber varies the light-emitting portion of the taper over several millimeters without movement of the implant...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28628100/hotspots-of-missense-mutation-identify-neurodevelopmental-disorder-genes-and-functional-domains
#5
Madeleine R Geisheker, Gabriel Heymann, Tianyun Wang, Bradley P Coe, Tychele N Turner, Holly A F Stessman, Kendra Hoekzema, Malin Kvarnung, Marie Shaw, Kathryn Friend, Jan Liebelt, Christopher Barnett, Elizabeth M Thompson, Eric Haan, Hui Guo, Britt-Marie Anderlid, Ann Nordgren, Anna Lindstrand, Geert Vandeweyer, Antonino Alberti, Emanuela Avola, Mirella Vinci, Stefania Giusto, Tiziano Pramparo, Karen Pierce, Srinivasa Nalabolu, Jacob J Michaelson, Zdenek Sedlacek, Gijs W E Santen, Hilde Peeters, Hakon Hakonarson, Eric Courchesne, Corrado Romano, R Frank Kooy, Raphael A Bernier, Magnus Nordenskjöld, Jozef Gecz, Kun Xia, Larry S Zweifel, Evan E Eichler
Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,688 patients with NDD identified 21 new patients with identical missense mutations...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28604685/a-tnf-jnk-axl-erk-signaling-axis-mediates-primary-resistance-to-egfr-inhibition-in-glioblastoma
#6
Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib
Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in turn of c-Jun N-terminal kinase (JNK), the Axl receptor tyrosine kinase and extracellular signal-regulated kinases (ERK)...
June 12, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28604684/sensory-integration-and-neuromodulatory-feedback-facilitate-drosophila-mechanonociceptive-behavior
#7
Chun Hu, Meike Petersen, Nina Hoyer, Bettina Spitzweck, Federico Tenedini, Denan Wang, Alisa Gruschka, Lara S Burchardt, Emanuela Szpotowicz, Michaela Schweizer, Ananya R Guntur, Chung-Hui Yang, Peter Soba
Nociception is an evolutionarily conserved mechanism to encode and process harmful environmental stimuli. Like most animals, Drosophila melanogaster larvae respond to a variety of nociceptive stimuli, including noxious touch and temperature, with stereotyped escape responses through activation of multimodal nociceptors. How behavioral responses to these different modalities are processed and integrated by the downstream network remains poorly understood. By combining trans-synaptic labeling, ultrastructural analysis, calcium imaging, optogenetics and behavioral analyses, we uncovered a circuit specific for mechanonociception but not thermonociception...
June 12, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28604683/neural-signatures-of-dynamic-stimulus-selection-in-drosophila
#8
Yi Sun, Aljoscha Nern, Romain Franconville, Hod Dana, Eric R Schreiter, Loren L Looger, Karel Svoboda, Douglas S Kim, Ann M Hermundstad, Vivek Jayaraman
Many animals orient using visual cues, but how a single cue is selected from among many is poorly understood. Here we show that Drosophila ring neurons-central brain neurons implicated in navigation-display visual stimulus selection. Using in vivo two-color two-photon imaging with genetically encoded calcium indicators, we demonstrate that individual ring neurons inherit simple-cell-like receptive fields from their upstream partners. Stimuli in the contralateral visual field suppressed responses to ipsilateral stimuli in both populations...
June 12, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28581480/rich-cell-type-specific-network-topology-in-neocortical-microcircuitry
#9
Eyal Gal, Michael London, Amir Globerson, Srikanth Ramaswamy, Michael W Reimann, Eilif Muller, Henry Markram, Idan Segev
Uncovering structural regularities and architectural topologies of cortical circuitry is vital for understanding neural computations. Recently, an experimentally constrained algorithm generated a dense network reconstruction of a ∼0.3-mm(3) volume from juvenile rat somatosensory neocortex, comprising ∼31,000 cells and ∼36 million synapses. Using this reconstruction, we found a small-world topology with an average of 2.5 synapses separating any two cells and multiple cell-type-specific wiring features...
June 5, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28581479/cancer-induced-anorexia-and-malaise-are-mediated-by-cgrp-neurons-in-the-parabrachial-nucleus
#10
Carlos A Campos, Anna J Bowen, Sung Han, Brent E Wisse, Richard D Palmiter, Michael W Schwartz
Anorexia is a common manifestation of chronic diseases, including cancer. Here we investigate the contribution to cancer anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. We show that CGRP(PBN) neurons are activated in mice implanted with Lewis lung carcinoma cells. Inactivation of CGRP(PBN) neurons before tumor implantation prevents anorexia and loss of lean mass, and their inhibition after symptom onset reverses anorexia. CGRP(PBN) neurons are also activated in Apc(min/+) mice, which develop intestinal cancer and lose weight despite the absence of reduced food intake...
June 5, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28581478/reinstated-episodic-context-guides-sampling-based-decisions-for-reward
#11
Aaron M Bornstein, Kenneth A Norman
How does experience inform decisions? In episodic sampling, decisions are guided by a few episodic memories of past choices. This process can yield choice patterns similar to model-free reinforcement learning; however, samples can vary from trial to trial, causing decisions to vary. Here we show that context retrieved during episodic sampling can cause choice behavior to deviate sharply from the predictions of reinforcement learning. Specifically, we show that, when a given memory is sampled, choices (in the present) are influenced by the properties of other decisions made in the same context as the sampled event...
June 5, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28553944/the-cellular-mechanism-for-water-detection-in-the-mammalian-taste-system
#12
Dhruv Zocchi, Gunther Wennemuth, Yuki Oka
Initiation of drinking behavior relies on both internal state and peripheral water detection. While central neural circuits regulating thirst have been well studied, it is still unclear how mammals recognize external water. Here we show that acid-sensing taste receptor cells (TRCs) that were previously suggested as the sour taste sensors also mediate taste responses to water. Genetic silencing of these TRCs abolished water-evoked responses in taste nerves. Optogenetic self-stimulation of acid-sensing TRCs in thirsty animals induced robust drinking responses toward light even without water...
May 29, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28553943/attention-related-changes-in-correlated-neuronal-activity-arise-from-normalization-mechanisms
#13
Bram-Ernst Verhoef, John H R Maunsell
Attention is believed to enhance perception by altering the activity-level correlations between pairs of neurons. How attention changes neuronal activity correlations is unknown. Using multielectrodes in monkey visual cortex, we measured spike-count correlations when single or multiple stimuli were presented and when stimuli were attended or unattended. When stimuli were unattended, adding a suppressive, nonpreferred stimulus beside a preferred stimulus increased spike-count correlations between pairs of similarly tuned neurons but decreased spike-count correlations between pairs of oppositely tuned neurons...
May 29, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28530664/flexible-information-routing-by-transient-synchrony
#14
Agostina Palmigiano, Theo Geisel, Fred Wolf, Demian Battaglia
Perception, cognition and behavior rely on flexible communication between microcircuits in distinct cortical regions. The mechanisms underlying rapid information rerouting between such microcircuits are still unknown. It has been proposed that changing patterns of coherence between local gamma rhythms support flexible information rerouting. The stochastic and transient nature of gamma oscillations in vivo, however, is hard to reconcile with such a function. Here we show that models of cortical circuits near the onset of oscillatory synchrony selectively route input signals despite the short duration of gamma bursts and the irregularity of neuronal firing...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28530663/a-cerebellum-like-circuit-in-the-auditory-system-cancels-responses-to-self-generated-sounds
#15
Shobhit Singla, Conor Dempsey, Richard Warren, Armen G Enikolopov, Nathaniel B Sawtell
The dorsal cochlear nucleus (DCN) integrates auditory nerve input with a diverse array of sensory and motor signals processed in circuitry similar to that of the cerebellum. Yet how the DCN contributes to early auditory processing has been a longstanding puzzle. Using electrophysiological recordings in mice during licking behavior, we show that DCN neurons are largely unaffected by self-generated sounds while remaining sensitive to external acoustic stimuli. Recordings in deafened mice, together with neural activity manipulations, indicate that self-generated sounds are cancelled by non-auditory signals conveyed by mossy fibers...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28530662/pd-l1-inhibits-acute-and-chronic-pain-by-suppressing-nociceptive-neuron-activity-via-pd-1
#16
Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28530661/causal-evidence-for-retina-dependent-and-independent-visual-motion-computations-in-mouse-cortex
#17
Daniel Hillier, Michele Fiscella, Antonia Drinnenberg, Stuart Trenholm, Santiago B Rompani, Zoltan Raics, Gergely Katona, Josephine Juettner, Andreas Hierlemann, Balazs Rozsa, Botond Roska
How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity, either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells, and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an over-representation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28504673/a-fluoro-nissl-dye-identifies-pericytes-as-distinct-vascular-mural-cells-during-in-vivo-brain-imaging
#18
Eyiyemisi C Damisah, Robert A Hill, Lei Tong, Katie N Murray, Jaime Grutzendler
Pericytes and smooth muscle cells are integral components of the brain microvasculature. However, no techniques exist to unambiguously identify these cell types, greatly limiting their investigation in vivo. Here we show that the fluorescent Nissl dye NeuroTrace 500/525 labels brain pericytes with specificity, allowing high-resolution optical imaging in the live mouse. We demonstrate that capillary pericytes are a population of mural cells with distinct morphological, molecular and functional features that do not overlap with precapillary or arteriolar smooth muscle actin-expressing cells...
May 15, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28504672/identification-of-a-motor-to-auditory-pathway-important-for-vocal-learning
#19
Todd F Roberts, Erin Hisey, Masashi Tanaka, Matthew G Kearney, Gaurav Chattree, Cindy F Yang, Nirao M Shah, Richard Mooney
Learning to vocalize depends on the ability to adaptively modify the temporal and spectral features of vocal elements. Neurons that convey motor-related signals to the auditory system are theorized to facilitate vocal learning, but the identity and function of such neurons remain unknown. Here we identify a previously unknown neuron type in the songbird brain that transmits vocal motor signals to the auditory cortex. Genetically ablating these neurons in juveniles disrupted their ability to imitate features of an adult tutor's song...
May 15, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28504671/reduced-sensory-synaptic-excitation-impairs-motor-neuron-function-via-kv2-1-in-spinal-muscular-atrophy
#20
Emily V Fletcher, Christian M Simon, John G Pagiazitis, Joshua I Chalif, Aleksandra Vukojicic, Estelle Drobac, Xiaojian Wang, George Z Mentis
Behavioral deficits in neurodegenerative diseases are often attributed to the selective dysfunction of vulnerable neurons via cell-autonomous mechanisms. Although vulnerable neurons are embedded in neuronal circuits, the contributions of their synaptic partners to disease process are largely unknown. Here we show that, in a mouse model of spinal muscular atrophy (SMA), a reduction in proprioceptive synaptic drive leads to motor neuron dysfunction and motor behavior impairments. In SMA mice or after the blockade of proprioceptive synaptic transmission, we observed a decrease in the motor neuron firing that could be explained by the reduction in the expression of the potassium channel Kv2...
May 15, 2017: Nature Neuroscience
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