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  • Author Correction: Dorsal hippocampus contributes to model-based planning
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-17
    Kevin J. Miller, Matthew M. Botvinick, Carlos D. Brody

    Author Correction: Dorsal hippocampus contributes to model-based planning Author Correction: Dorsal hippocampus contributes to model-based planning, Published online: 17 November 2017; doi:10.1038/s41593-017-0026-8

    更新日期:2017-11-19
  • Author Correction: Dorsal hippocampus contributes to model-based planning
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-17
    Kevin J. Miller, Matthew M. Botvinick, Carlos D. Brody

    Author Correction: Dorsal hippocampus contributes to model-based planning Author Correction: Dorsal hippocampus contributes to model-based planning, Published online: 17 November 2017; doi:10.1038/s41593-017-0026-8

    更新日期:2017-11-19
  • A multiregional proteomic survey of the postnatal human brain
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Becky C. Carlyle, Robert R. Kitchen, Jean E. Kanyo, Edward Z. Voss, Mihovil Pletikos, André M. M. Sousa, TuKiet T. Lam, Mark B. Gerstein, Nenad Sestan, Angus C. Nairn

    Detailed observations of transcriptional, translational and post-translational events in the human brain are essential to improving our understanding of its development, function and vulnerability to disease. Here, we exploited label-free quantitative tandem mass-spectrometry to create an in-depth proteomic survey of regions of the postnatal human brain, ranging in age from early infancy to adulthood. Integration of protein data with existing matched whole-transcriptome sequencing (RNA-seq) from the BrainSpan project revealed varied patterns of protein–RNA relationships, with generally increased magnitudes of protein abundance differences between brain regions compared to RNA. Many of the differences amplified in protein data were reflective of cytoarchitectural and functional variation between brain regions. Comparing structurally similar cortical regions revealed significant differences in the abundances of receptor-associated and resident plasma membrane proteins that were not readily observed in the RNA expression data.

    更新日期:2017-11-13
  • Lateral geniculate neurons projecting to primary visual cortex show ocular dominance plasticity in adult mice
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Juliane Jaepel, Mark Hübener, Tobias Bonhoeffer, Tobias Rose

    Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca2+ imaging of thalamic afferents in layer 1 of binocular visual cortex, we provide evidence against this tenet: the respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced ocular dominance (OD) shifts after monocular deprivation in adult mice. Most (86%), but not all, of dLGN cell boutons were monocular during normal visual experience. Following deprivation, initially deprived-eye-dominated boutons reduced or lost their visual responsiveness to that eye and frequently became responsive to the non-deprived eye. This cannot be explained by eye-specific cortical changes propagating to dLGN via cortico-thalamic feedback because the shift in dLGN responses was largely resistant to cortical inactivation using the GABAA receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partially reflect plasticity of eye-specific inputs onto dLGN neurons.

    更新日期:2017-11-13
  • Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid intake
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Philip J. Ryan, Silvano I. Ross, Carlos A. Campos, Victor A. Derkach, Richard D. Palmiter

    Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (OxtrPBN neurons) are key regulators of fluid satiation. Chemogenetic activation of OxtrPBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, OxtrPBN neurons were activated by fluid satiation and hypertonic saline injection. OxtrPBN neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (OxtPVH neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated OxtrPBN neurons. Our results suggest that OxtrPBN neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.

    更新日期:2017-11-13
  • A craniofacial-specific monosynaptic circuit enables heightened affective pain
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Erica Rodriguez, Katsuyasu Sakurai, Jennie Xu, Yong Chen, Koji Toda, Shengli Zhao, Bao-Xia Han, David Ryu, Henry Yin, Wolfgang Liedtke, Fan Wang

    Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facial versus bodily pain remains unknown. Interestingly, the lateral parabrachial nucleus (PBL), a critical node in the affective pain circuit, is activated more strongly by noxious stimulation of the face than of the hindpaw. Using a novel activity-dependent technology called CANE developed in our laboratory, we identified and selectively labeled noxious-stimulus-activated PBL neurons and performed comprehensive anatomical input–output mapping. Surprisingly, we uncovered a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PBL-nociceptive neurons. Optogenetic activation of this monosynaptic craniofacial-to-PBL projection induced robust escape and avoidance behaviors and stress calls, whereas optogenetic silencing specifically reduced facial nociception. The monosynaptic circuit revealed here provides a neural substrate for heightened craniofacial affective pain.

    更新日期:2017-11-13
  • Temporally precise single-cell-resolution optogenetics
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Or A. Shemesh, Dimitrii Tanese, Valeria Zampini, Changyang Linghu, Kiryl Piatkevich, Emiliano Ronzitti, Eirini Papagiakoumou, Edward S. Boyden, Valentina Emiliani

    Optogenetic control of individual neurons with high temporal precision within intact mammalian brain circuitry would enable powerful explorations of how neural circuits operate. Two-photon computer-generated holography enables precise sculpting of light and could in principle enable simultaneous illumination of many neurons in a network, with the requisite temporal precision to simulate accurate neural codes. We designed a high-efficacy soma-targeted opsin, finding that fusing the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to the recently discovered high-photocurrent channelrhodopsin CoChR restricted expression of this opsin primarily to the cell body of mammalian cortical neurons. In combination with two-photon holographic stimulation, we found that this somatic CoChR (soCoChR) enabled photostimulation of individual cells in mouse cortical brain slices with single-cell resolution and <1-ms temporal precision. We used soCoChR to perform connectivity mapping on intact cortical circuits.

    更新日期:2017-11-13
  • Social stress induces neurovascular pathology promoting depression
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Caroline Menard, Madeline L. Pfau, Georgia E. Hodes, Veronika Kana, Victoria X. Wang, Sylvain Bouchard, Aki Takahashi, Meghan E. Flanigan, Hossein Aleyasin, Katherine B. LeClair, William G. Janssen, Benoit Labonté, Eric M. Parise, Zachary S. Lorsch, Sam A. Golden, Mitra Heshmati, Carol Tamminga, Gustavo Turecki, Matthew Campbell, Zahi A. Fayad, Cheuk Ying Tang, Miriam Merad, Scott J. Russo

    Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression.

    更新日期:2017-11-13
  • A multiregional proteomic survey of the postnatal human brain
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Becky C. Carlyle, Robert R. Kitchen, Jean E. Kanyo, Edward Z. Voss, Mihovil Pletikos, André M. M. Sousa, TuKiet T. Lam, Mark B. Gerstein, Nenad Sestan, Angus C. Nairn

    Detailed observations of transcriptional, translational and post-translational events in the human brain are essential to improving our understanding of its development, function and vulnerability to disease. Here, we exploited label-free quantitative tandem mass-spectrometry to create an in-depth proteomic survey of regions of the postnatal human brain, ranging in age from early infancy to adulthood. Integration of protein data with existing matched whole-transcriptome sequencing (RNA-seq) from the BrainSpan project revealed varied patterns of protein–RNA relationships, with generally increased magnitudes of protein abundance differences between brain regions compared to RNA. Many of the differences amplified in protein data were reflective of cytoarchitectural and functional variation between brain regions. Comparing structurally similar cortical regions revealed significant differences in the abundances of receptor-associated and resident plasma membrane proteins that were not readily observed in the RNA expression data.

    更新日期:2017-11-13
  • Lateral geniculate neurons projecting to primary visual cortex show ocular dominance plasticity in adult mice
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Juliane Jaepel, Mark Hübener, Tobias Bonhoeffer, Tobias Rose

    Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca2+ imaging of thalamic afferents in layer 1 of binocular visual cortex, we provide evidence against this tenet: the respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced ocular dominance (OD) shifts after monocular deprivation in adult mice. Most (86%), but not all, of dLGN cell boutons were monocular during normal visual experience. Following deprivation, initially deprived-eye-dominated boutons reduced or lost their visual responsiveness to that eye and frequently became responsive to the non-deprived eye. This cannot be explained by eye-specific cortical changes propagating to dLGN via cortico-thalamic feedback because the shift in dLGN responses was largely resistant to cortical inactivation using the GABAA receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partially reflect plasticity of eye-specific inputs onto dLGN neurons.

    更新日期:2017-11-13
  • Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid intake
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Philip J. Ryan, Silvano I. Ross, Carlos A. Campos, Victor A. Derkach, Richard D. Palmiter

    Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (OxtrPBN neurons) are key regulators of fluid satiation. Chemogenetic activation of OxtrPBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, OxtrPBN neurons were activated by fluid satiation and hypertonic saline injection. OxtrPBN neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (OxtPVH neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated OxtrPBN neurons. Our results suggest that OxtrPBN neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.

    更新日期:2017-11-13
  • A craniofacial-specific monosynaptic circuit enables heightened affective pain
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Erica Rodriguez, Katsuyasu Sakurai, Jennie Xu, Yong Chen, Koji Toda, Shengli Zhao, Bao-Xia Han, David Ryu, Henry Yin, Wolfgang Liedtke, Fan Wang

    Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facial versus bodily pain remains unknown. Interestingly, the lateral parabrachial nucleus (PBL), a critical node in the affective pain circuit, is activated more strongly by noxious stimulation of the face than of the hindpaw. Using a novel activity-dependent technology called CANE developed in our laboratory, we identified and selectively labeled noxious-stimulus-activated PBL neurons and performed comprehensive anatomical input–output mapping. Surprisingly, we uncovered a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PBL-nociceptive neurons. Optogenetic activation of this monosynaptic craniofacial-to-PBL projection induced robust escape and avoidance behaviors and stress calls, whereas optogenetic silencing specifically reduced facial nociception. The monosynaptic circuit revealed here provides a neural substrate for heightened craniofacial affective pain.

    更新日期:2017-11-13
  • Temporally precise single-cell-resolution optogenetics
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Or A. Shemesh, Dimitrii Tanese, Valeria Zampini, Changyang Linghu, Kiryl Piatkevich, Emiliano Ronzitti, Eirini Papagiakoumou, Edward S. Boyden, Valentina Emiliani

    Optogenetic control of individual neurons with high temporal precision within intact mammalian brain circuitry would enable powerful explorations of how neural circuits operate. Two-photon computer-generated holography enables precise sculpting of light and could in principle enable simultaneous illumination of many neurons in a network, with the requisite temporal precision to simulate accurate neural codes. We designed a high-efficacy soma-targeted opsin, finding that fusing the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to the recently discovered high-photocurrent channelrhodopsin CoChR restricted expression of this opsin primarily to the cell body of mammalian cortical neurons. In combination with two-photon holographic stimulation, we found that this somatic CoChR (soCoChR) enabled photostimulation of individual cells in mouse cortical brain slices with single-cell resolution and <1-ms temporal precision. We used soCoChR to perform connectivity mapping on intact cortical circuits.

    更新日期:2017-11-13
  • Social stress induces neurovascular pathology promoting depression
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-13
    Caroline Menard, Madeline L. Pfau, Georgia E. Hodes, Veronika Kana, Victoria X. Wang, Sylvain Bouchard, Aki Takahashi, Meghan E. Flanigan, Hossein Aleyasin, Katherine B. LeClair, William G. Janssen, Benoit Labonté, Eric M. Parise, Zachary S. Lorsch, Sam A. Golden, Mitra Heshmati, Carol Tamminga, Gustavo Turecki, Matthew Campbell, Zahi A. Fayad, Cheuk Ying Tang, Miriam Merad, Scott J. Russo

    Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression.

    更新日期:2017-11-13
  • Weak correlations between hemodynamic signals and ongoing neural activity during the resting state
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-06
    Aaron T. Winder, Christina Echagarruga, Qingguang Zhang, Patrick J. Drew

    Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt stimulation are used to infer neural activity. We tested this coupling by simultaneously measuring neural activity and changes in cerebral blood volume (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of true rest and during whisker stimulation and volitional whisking. We found that neurovascular coupling was similar across states and that large, spontaneous CBV changes in the absence of sensory input were driven by volitional whisker and body movements. Hemodynamic signals during periods of rest were weakly correlated with neural activity. Spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking and glutamatergic input were blocked, as well as during blockade of noradrenergic receptors, suggesting a non-neuronal origin for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a combination of behavior, local neural activity, and putatively non-neural processes.

    更新日期:2017-11-06
  • Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-06
    Eui-Man Jung, Jeffrey Jay Moffat, Jinxu Liu, Shashank Manohar Dravid, Channabasavaiah Basavaraju Gurumurthy, Woo-Yang Kim

    Haploinsufficiency of the AT-rich interactive domain 1B (ARID1B) gene causes autism spectrum disorder and intellectual disability; however, the neurobiological basis for this is unknown. Here we generated Arid1b-knockout mice and examined heterozygotes to model human patients. Arid1b-heterozygous mice showed a decreased number of cortical GABAergic interneurons and reduced proliferation of interneuron progenitors in the ganglionic eminence. Arid1b haploinsufficiency also led to an imbalance between excitatory and inhibitory synapses in the cerebral cortex. Furthermore, we found that Arid1b haploinsufficiency suppressed histone H3 lysine 9 acetylation (H3K9ac) overall and particularly reduced H3K9ac of the Pvalb promoter, resulting in decreased transcription. Arid1b-heterozygous mice exhibited abnormal cognitive and social behaviors, which were rescued by treatment with a positive allosteric GABAA receptor modulator. Our results demonstrate a critical role for Arid1b in interneuron development and behavior and provide insight into the pathogenesis of autism spectrum disorder and intellectual disability.

    更新日期:2017-11-06
  • Weak correlations between hemodynamic signals and ongoing neural activity during the resting state
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-06
    Aaron T. Winder, Christina Echagarruga, Qingguang Zhang, Patrick J. Drew

    Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt stimulation are used to infer neural activity. We tested this coupling by simultaneously measuring neural activity and changes in cerebral blood volume (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of true rest and during whisker stimulation and volitional whisking. We found that neurovascular coupling was similar across states and that large, spontaneous CBV changes in the absence of sensory input were driven by volitional whisker and body movements. Hemodynamic signals during periods of rest were weakly correlated with neural activity. Spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking and glutamatergic input were blocked, as well as during blockade of noradrenergic receptors, suggesting a non-neuronal origin for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a combination of behavior, local neural activity, and putatively non-neural processes.

    更新日期:2017-11-06
  • Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-06
    Eui-Man Jung, Jeffrey Jay Moffat, Jinxu Liu, Shashank Manohar Dravid, Channabasavaiah Basavaraju Gurumurthy, Woo-Yang Kim

    Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior <i>Arid1b</i> haploinsufficiency disrupts cortical interneuron development and mouse behavior, Published online: 06 November 2017; doi:10.1038/s41593-017-0013-0NatureArticleSnippet(type=short-summary, markup= Arid1b haploinsufficiency causes autism and intellectual disability, yet the neurobiological basis of this is unknown. The authors demonstrate that Arid1b-heterozygous mice have impaired cortical interneuron development and epigenetic signatures. These mice also have cognitive and social deficits, which are reversed by treatment with a GABAA-receptor-positive allosteric modulator., isJats=true)

    更新日期:2017-11-06
  • Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-10-30
    Catherine J. Stoodley, Anila M. D’Mello, Jacob Ellegood, Vikram Jakkamsetti, Pei Liu, Mary Beth Nebel, Jennifer M. Gibson, Elyza Kelly, Fantao Meng, Christopher A. Cano, Juan M. Pascual, Stewart H. Mostofsky, Jason P. Lerch, Peter T. Tsai

    Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI–inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

    更新日期:2017-10-30
  • Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-10-30
    Catherine J. Stoodley, Anila M. D’Mello, Jacob Ellegood, Vikram Jakkamsetti, Pei Liu, Mary Beth Nebel, Jennifer M. Gibson, Elyza Kelly, Fantao Meng, Christopher A. Cano, Juan M. Pascual, Stewart H. Mostofsky, Jason P. Lerch, Peter T. Tsai

    Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI–inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

    更新日期:2017-10-30
  • Spatial representation in the hippocampal formation: a history
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Edvard I Moser, May-Britt Moser, Bruce L McNaughton

    Spatial representation in the hippocampal formation: a history Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4653 Moser, Moser and McNaughton provide a historical overview describing how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal–entorhinal systems, from the discovery of place cells in the 1970s to contemporary studies of spatial coding in intermingled and interacting cell types within complex circuits.

    更新日期:2017-10-30
  • Integration of objects and space in perception and memory
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Charles E Connor, James J Knierim

    Distinct processing of objects and space has been an organizing principle for studying higher-level vision and medial temporal lobe memory. Here, however, we discuss how object and spatial information are in fact closely integrated in vision and memory. The ventral, object-processing visual pathway carries precise spatial information, transformed from retinotopic coordinates into relative dimensions. At the final stages of the ventral pathway, including the dorsal anterior temporal lobe (TEd), object-sensitive neurons are intermixed with neurons that process large-scale environmental space. TEd projects primarily to perirhinal cortex (PRC), which in turn projects to lateral entorhinal cortex (LEC). PRC and LEC also combine object and spatial information. For example, PRC and LEC neurons exhibit place fields that are evoked by landmark objects or the remembered locations of objects. Thus, spatial information, on both local and global scales, is deeply integrated into the ventral (temporal) object-processing pathway in vision and memory.

    更新日期:2017-10-30
  • Viewpoints: how the hippocampus contributes to memory, navigation and cognition
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    John Lisman, György Buzsáki, Howard Eichenbaum, Lynn Nadel, Charan Rangananth, A David Redish

    The hippocampus serves a critical function in memory, navigation, and cognition. Nature Neuroscience asked John Lisman to lead a group of researchers in a dialog on shared and distinct viewpoints on the hippocampus.

    更新日期:2017-10-30
  • Howard Eichenbaum 1947–2017
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Marc Howard, Chantal E Stern, Michael E Hasselmo

    Howard Eichenbaum 1947–2017 Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4659

    更新日期:2017-10-30
  • Polymorphic computation in locus coeruleus networks
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Dong-oh Seo, Michael R Bruchas

    Physiological and optogenetic dissection of discrete locus coeruleus neuronal populations reveals a functional disassociation, with heterogeneous engagement of locus coeruleus neurons in either fear learning or extinction models.

    更新日期:2017-10-30
  • Synaptic integrative mechanisms for spatial cognition
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Christoph Schmidt-Hieber, Matthew F Nolan

    Synaptic integrative mechanisms have profound effects on electrical signaling in the brain that, although largely hidden from recording methods that observe the spiking activity of neurons, may be critical for the encoding, storage and retrieval of information. Here we review roles for synaptic integrative mechanisms in the selection, generation and plasticity of place and grid fields, and in related temporal codes for the representation of space. We outline outstanding questions and challenges in the testing of hypothesized models for spatial computation and memory.

    更新日期:2017-10-30
  • Cell types for our sense of location: where we are and where we are going
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Kiah Hardcastle, Surya Ganguli, Lisa M Giocomo

    Technological advances in profiling cells along genetic, anatomical and physiological axes have fomented interest in identifying all neuronal cell types. This goal nears completion in specialized circuits such as the retina, while remaining more elusive in higher order cortical regions. We propose that this differential success of cell type identification may not simply reflect technological gaps in co-registering genetic, anatomical and physiological features in the cortex. Rather, we hypothesize it reflects evolutionarily driven differences in the computational principles governing specialized circuits versus more general-purpose learning machines. In this framework, we consider the question of cell types in medial entorhinal cortex (MEC), a region likely to be involved in memory and navigation. While MEC contains subsets of identifiable functionally defined cell types, recent work employing unbiased statistical methods and more diverse tasks reveals unsuspected heterogeneity and adaptivity in MEC firing patterns. This suggests MEC may operate more as a generalist circuit, obeying computational design principles resembling those governing other higher cortical regions.

    更新日期:2017-10-30
  • The cognitive map in humans: spatial navigation and beyond
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Russell A Epstein, Eva Zita Patai, Joshua B Julian, Hugo J Spiers

    The 'cognitive map' hypothesis proposes that brain builds a unified representation of the spatial environment to support memory and guide future action. Forty years of electrophysiological research in rodents suggest that cognitive maps are neurally instantiated by place, grid, border and head direction cells in the hippocampal formation and related structures. Here we review recent work that suggests a similar functional organization in the human brain and yields insights into how cognitive maps are used during spatial navigation. Specifically, these studies indicate that (i) the human hippocampus and entorhinal cortex support map-like spatial codes, (ii) posterior brain regions such as parahippocampal and retrosplenial cortices provide critical inputs that allow cognitive maps to be anchored to fixed environmental landmarks, and (iii) hippocampal and entorhinal spatial codes are used in conjunction with frontal lobe mechanisms to plan routes during navigation. We also discuss how these three basic elements of cognitive map based navigation—spatial coding, landmark anchoring and route planning—might be applied to nonspatial domains to provide the building blocks for many core elements of human thought.

    更新日期:2017-10-30
  • Spatial representation in the hippocampal formation: a history
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Edvard I Moser, May-Britt Moser, Bruce L McNaughton

    Spatial representation in the hippocampal formation: a history Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4653 Moser, Moser and McNaughton provide a historical overview describing how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal–entorhinal systems, from the discovery of place cells in the 1970s to contemporary studies of spatial coding in intermingled and interacting cell types within complex circuits.

    更新日期:2017-10-30
  • Integration of objects and space in perception and memory
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Charles E Connor, James J Knierim

    Distinct processing of objects and space has been an organizing principle for studying higher-level vision and medial temporal lobe memory. Here, however, we discuss how object and spatial information are in fact closely integrated in vision and memory. The ventral, object-processing visual pathway carries precise spatial information, transformed from retinotopic coordinates into relative dimensions. At the final stages of the ventral pathway, including the dorsal anterior temporal lobe (TEd), object-sensitive neurons are intermixed with neurons that process large-scale environmental space. TEd projects primarily to perirhinal cortex (PRC), which in turn projects to lateral entorhinal cortex (LEC). PRC and LEC also combine object and spatial information. For example, PRC and LEC neurons exhibit place fields that are evoked by landmark objects or the remembered locations of objects. Thus, spatial information, on both local and global scales, is deeply integrated into the ventral (temporal) object-processing pathway in vision and memory.

    更新日期:2017-10-30
  • Viewpoints: how the hippocampus contributes to memory, navigation and cognition
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    John Lisman, György Buzsáki, Howard Eichenbaum, Lynn Nadel, Charan Rangananth, A David Redish

    Viewpoints: how the hippocampus contributes to memory, navigation and cognition Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4661 The hippocampus serves a critical function in memory, navigation, and cognition. Nature Neuroscience asked John Lisman to lead a group of researchers in a dialog on shared and distinct viewpoints on the hippocampus.

    更新日期:2017-10-30
  • Howard Eichenbaum 1947–2017
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Marc Howard, Chantal E Stern, Michael E Hasselmo

    Howard Eichenbaum 1947–2017 Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4659

    更新日期:2017-10-30
  • Polymorphic computation in locus coeruleus networks
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Dong-oh Seo, Michael R Bruchas

    Polymorphic computation in locus coeruleus networks Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4663 Physiological and optogenetic dissection of discrete locus coeruleus neuronal populations reveals a functional disassociation, with heterogeneous engagement of locus coeruleus neurons in either fear learning or extinction models.

    更新日期:2017-10-30
  • Synaptic integrative mechanisms for spatial cognition
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Christoph Schmidt-Hieber, Matthew F Nolan

    Synaptic integrative mechanisms for spatial cognition Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4652 Synaptic integration is critical for determining how information in the brain is encoded, stored and retrieved. The authors review roles for synaptic integrative mechanisms in the selection, generation and plasticity of spatially modulated firing, and in related temporal codes for representation of space.

    更新日期:2017-10-30
  • Cell types for our sense of location: where we are and where we are going
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Kiah Hardcastle, Surya Ganguli, Lisa M Giocomo

    Cell types for our sense of location: where we are and where we are going Nature Neuroscience, Published online: 26 October 2017; doi:10.1038/nn.4654 In this Perspective, the authors propose that functional insights into generalist cortical computation may reside at the level of population patterns rather than functionally defined cell types. They then review results showing that medial entorhinal cortex (MEC) neurons exhibit substantial heterogeneity, suggesting MEC is a generalist circuit that computes diverse episodic states.

    更新日期:2017-10-30
  • The cognitive map in humans: spatial navigation and beyond
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-11-01
    Russell A Epstein, Eva Zita Patai, Joshua B Julian, Hugo J Spiers

    The 'cognitive map' hypothesis proposes that brain builds a unified representation of the spatial environment to support memory and guide future action. Forty years of electrophysiological research in rodents suggest that cognitive maps are neurally instantiated by place, grid, border and head direction cells in the hippocampal formation and related structures. Here we review recent work that suggests a similar functional organization in the human brain and yields insights into how cognitive maps are used during spatial navigation. Specifically, these studies indicate that (i) the human hippocampus and entorhinal cortex support map-like spatial codes, (ii) posterior brain regions such as parahippocampal and retrosplenial cortices provide critical inputs that allow cognitive maps to be anchored to fixed environmental landmarks, and (iii) hippocampal and entorhinal spatial codes are used in conjunction with frontal lobe mechanisms to plan routes during navigation. We also discuss how these three basic elements of cognitive map based navigation—spatial coding, landmark anchoring and route planning—might be applied to nonspatial domains to provide the building blocks for many core elements of human thought.

    更新日期:2017-10-30
  • Thalamic inhibition regulates critical-period plasticity in visual cortex and thalamus
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Jean-Pierre Sommeijer, Mehran Ahmadlou, M. Hadi Saiepour, Koen Seignette, Rogier Min, J. Alexander Heimel, Christiaan N. Levelt

    During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses within V1, specifically those containing the GABAA receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.

    更新日期:2017-10-16
  • Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for animal nociception
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Oscar M. Arenas, Emanuela E. Zaharieva, Alessia Para, Constanza Vásquez-Doorman, Christian P. Petersen, Marco Gallio

    All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea and that the conserved ion channel TRPA1 is required for these responses. TRPA1-mutant Drosophila flies are also defective in noxious-heat responses. We find that either planarian or human TRPA1 can restore noxious-heat avoidance to TRPA1-mutant Drosophila, although neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2 and reactive oxygen species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago.

    更新日期:2017-10-16
  • Mixed selectivity morphs population codes in prefrontal cortex
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Aishwarya Parthasarathy, Roger Herikstad, Jit Hon Bong, Felipe Salvador Medina, Camilo Libedinsky, Shih-Cheng Yen

    The prefrontal cortex maintains working memory information in the presence of distracting stimuli. It has long been thought that sustained activity in individual neurons or groups of neurons was responsible for maintaining information in the form of a persistent, stable code. Here we show that, upon the presentation of a distractor, information in the lateral prefrontal cortex was reorganized into a different pattern of activity to create a morphed stable code without losing information. In contrast, the code in the frontal eye fields persisted across different delay periods but exhibited substantial instability and information loss after the presentation of a distractor. We found that neurons with mixed-selective responses were necessary and sufficient for the morphing of code and that these neurons were more abundant in the lateral prefrontal cortex than the frontal eye fields. This suggests that mixed selectivity provides populations with code-morphing capability, a property that may underlie cognitive flexibility.

    更新日期:2017-10-11
  • Cellular and oscillatory substrates of fear extinction learning
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Patrick Davis, Yosif Zaki, Jamie Maguire, Leon G Reijmers

    The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a combination of chemogenetics, activity-based neuronal-ensemble labeling and in vivo electrophysiology, we found that fear extinction learning confers on parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6–12 Hz oscillation and a fear-associated 3–6 Hz oscillation within the BLA. Loss of this competition increases a 3–6 Hz oscillatory signature, with BLAmedial prefrontal cortex directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.

    更新日期:2017-10-11
  • The hippocampus as a predictive map
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Kimberly L Stachenfeld, Matthew M Botvinick, Samuel J Gershman

    A cognitive map has long been the dominant metaphor for hippocampal function, embracing the idea that place cells encode a geometric representation of space. However, evidence for predictive coding, reward sensitivity and policy dependence in place cells suggests that the representation is not purely spatial. We approach this puzzle from a reinforcement learning perspective: what kind of spatial representation is most useful for maximizing future reward? We show that the answer takes the form of a predictive representation. This representation captures many aspects of place cell responses that fall outside the traditional view of a cognitive map. Furthermore, we argue that entorhinal grid cells encode a low-dimensionality basis set for the predictive representation, useful for suppressing noise in predictions and extracting multiscale structure for hierarchical planning.

    更新日期:2017-10-11
  • Cerebellar granule cell replenishment postinjury by adaptive reprogramming of Nestin+ progenitors
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-08-14
    Alexandre Wojcinski, Andrew K Lawton, N Sumru Bayin, Zhimin Lao, Daniel N Stephen, Alexandra L Joyner

    Recovery of the developing cerebellum after depletion of granule cells, the most plentiful neuron population, depends on adaptive reprogramming of neural progenitors to a new fate and a powerful cell–cell communication system that ensures re-establishment of the correct proportions of different cerebellar cell types and normal circuit formation.

    更新日期:2017-09-28
  • Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-08-28
    Petra Füger, Jasmin K Hefendehl, Karthik Veeraraghavalu, Ann-Christin Wendeln, Christine Schlosser, Ulrike Obermüller, Bettina M Wegenast-Braun, Jonas J Neher, Peter Martus, Shinichi Kohsaka, Martin Thunemann, Robert Feil, Sangram S Sisodia, Angelos Skodras, Mathias Jucker

    To clarify the role of microglia in brain homeostasis and disease, an understanding of their maintenance, proliferation and turnover is essential. The lifespan of brain microglia, however, remains uncertain, and reflects confounding factors in earlier assessments that were largely indirect. We genetically labeled single resident microglia in living mice and then used multiphoton microscopy to monitor these cells over time. Under homeostatic conditions, we found that neocortical resident microglia were long-lived, with a median lifetime of well over 15 months; thus, approximately half of these cells survive the entire mouse lifespan. While proliferation of resident neocortical microglia under homeostatic conditions was low, microglial proliferation in a mouse model of Alzheimer's β-amyloidosis was increased threefold. The persistence of individual microglia throughout the mouse lifespan provides an explanation for how microglial priming early in life can induce lasting functional changes and how microglial senescence may contribute to age-related neurodegenerative diseases.

    更新日期:2017-09-28
  • Selective inhibitory control of pyramidal neuron ensembles and cortical subnetworks by chandelier cells
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-08-21
    Jiangteng Lu, Jason Tucciarone, Nancy Padilla-Coreano, Miao He, Joshua A Gordon, Z Josh Huang

    The neocortex comprises multiple information processing streams mediated by subsets of glutamatergic pyramidal cells (PCs) that receive diverse inputs and project to distinct targets. How GABAergic interneurons regulate the segregation and communication among intermingled PC subsets that contribute to separate brain networks remains unclear. Here we demonstrate that a subset of GABAergic chandelier cells (ChCs) in the prelimbic cortex, which innervate PCs at spike initiation site, selectively control PCs projecting to the basolateral amygdala (BLAPC) compared to those projecting to contralateral cortex (CCPC). These ChCs in turn receive preferential input from local and contralateral CCPCs as opposed to BLAPCs and BLA neurons (the prelimbic cortex–BLA network). Accordingly, optogenetic activation of ChCs rapidly suppresses BLAPCs and BLA activity in freely behaving mice. Thus, the exquisite connectivity of ChCs not only mediates directional inhibition between local PC ensembles but may also shape communication hierarchies between global networks.

    更新日期:2017-09-28
  • Central amygdala circuits modulate food consumption through a positive-valence mechanism
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-08-21
    Amelia M Douglass, Hakan Kucukdereli, Marion Ponserre, Milica Markovic, Jan Gründemann, Cornelia Strobel, Pilar L Alcala Morales, Karl-Klaus Conzelmann, Andreas Lüthi, Rüdiger Klein

    The complex behaviors underlying reward seeking and consumption are integral to organism survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is poorly understood. The central nucleus of the amygdala (CeA) has been implicated in feeding and reward, but the neurons and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we defined the neuronal mechanisms by which CeA neurons promote food consumption. Using in vivo activity manipulations and Ca2+ imaging in mice, we found that GABAergic serotonin receptor 2a (Htr2a)-expressing CeA neurons modulate food consumption, promote positive reinforcement and are active in vivo during eating. We demonstrated electrophysiologically, anatomically and behaviorally that intra-CeA and long-range circuit mechanisms underlie these behaviors. Finally, we showed that CeAHtr2a neurons receive inputs from feeding-relevant brain regions. Our results illustrate how defined CeA neural circuits positively regulate food consumption.

    更新日期:2017-09-28
  • Parallel encoding of recent visual experience and self-motion during navigation in Drosophila
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-09-04
    Hiroshi M Shiozaki, Hokto Kazama

    Animal navigation requires multiple types of information for decisions on directional heading. We identified neural processing channels that encode multiple cues during navigational decision-making in Drosophila melanogaster. In a flight simulator, we found that flies made directional choices on the basis of the location of a recently presented landmark. This experience-guided navigation was impaired by silencing neurons in the bulb (BU), a region in the central brain. Two-photon calcium imaging during flight revealed that the dorsal part of the BU encodes the location of a recent landmark, whereas the ventral part of the BU tracks self-motion reflecting turns. Photolabeling-based circuit tracing indicated that these functional compartments of the BU constitute adjacent, yet distinct, anatomical pathways that both enter the navigation center. Thus, the fly's navigation system organizes multiple types of information in parallel channels, which may compactly transmit signals without interference for decision-making during flight.

    更新日期:2017-09-28
  • Seeing faces is necessary for face-domain formation
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-09-04
    Michael J Arcaro, Peter F Schade, Justin L Vincent, Carlos R Ponce, Margaret S Livingstone

    Here we report that monkeys raised without exposure to faces did not develop face domains, but did develop domains for other categories and did show normal retinotopic organization, indicating that early face deprivation leads to a highly selective cortical processing deficit. Therefore, experience must be necessary for the formation (or maintenance) of face domains. Gaze tracking revealed that control monkeys looked preferentially at faces, even at ages prior to the emergence of face domains, but face-deprived monkeys did not, indicating that face looking is not innate. A retinotopic organization is present throughout the visual system at birth, so selective early viewing behavior could bias category-specific visual responses toward particular retinotopic representations, thereby leading to domain formation in stereotyped locations in inferotemporal cortex, without requiring category-specific templates or biases. Thus, we propose that environmental importance influences viewing behavior, viewing behavior drives neuronal activity, and neuronal activity sculpts domain formation.

    更新日期:2017-09-28
  • Selective attention within the foveola
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-08-14
    Martina Poletti, Michele Rucci, Marisa Carrasco

    Efficient control of attentional resources and high-acuity vision are both fundamental for survival. Shifts in visual attention are known to covertly enhance processing at locations away from the center of gaze, where visual resolution is low. It is unknown, however, whether selective spatial attention operates where the observer is already looking—that is, within the high-acuity foveola, the small yet disproportionally important rod-free region of the retina. Using new methods for precisely controlling retinal stimulation, here we show that covert attention flexibly improves and speeds up both detection and discrimination at loci only a fraction of a degree apart within the foveola. These findings reveal a surprisingly precise control of attention and its involvement in fine spatial vision. They show that the commonly studied covert shifts of attention away from the fovea are the expression of a global mechanism that exerts its action across the entire visual field.

    更新日期:2017-09-28
  • An xQTL map integrates the genetic architecture of the human brain's transcriptome and epigenome
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-09-04
    Bernard Ng, Charles C White, Hans-Ulrich Klein, Solveig K Sieberts, Cristin McCabe, Ellis Patrick, Jishu Xu, Lei Yu, Chris Gaiteri, David A Bennett, Sara Mostafavi, Philip L De Jager

    This paper reports the availability of a new Resource with RNA-seq, DNA methylation and H3K9Ac QTL results from 411 brain samples. Many xQTL SNPs influence multiple molecular features, and the authors observe epigenetic mediation of eQTLs in some cases. Reanalyzing GWAS with an xQTL-weighted approach detected 20 new CNS disease susceptibility loci.

    更新日期:2017-09-28
  • Yummy or yucky? Ask your central amygdala
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Yoav Livneh, Mark L Andermann

    Yummy or yucky? Ask your central amygdala Nature Neuroscience, Published online: 26 September 2017; doi:10.1038/nn.4639 Central amygdala directs behavioral responses to emotionally salient stimuli. While most studies have focused on aversive responses, some central amygdala neurons promote feeding and are positively reinforcing.

    更新日期:2017-09-26
  • Corrigendum: Overlearning hyperstabilizes a skill by rapidly making neurochemical processing inhibitory-dominant
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Kazuhisa Shibata, Yuka Sasaki, Ji Won Bang, Edward G Walsh, Maro G Machizawa, Masako Tamaki, Li-Hung Chang, Takeo Watanabe

    Corrigendum: Overlearning hyperstabilizes a skill by rapidly making neurochemical processing inhibitory-dominant Nature Neuroscience, Published online: 26 September 2017; doi:10.1038/nn1017-1427b

    更新日期:2017-09-26
  • Unexpected help to repair the cerebellum
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Baptiste N Jaeger, Sebastian Jessberger

    Unexpected help to repair the cerebellum Nature Neuroscience, Published online: 26 September 2017; doi:10.1038/nn.4640 Upon injury of the developing mouse cerebellum, endogenous repair mechanisms can heal the brain and prevent behavioral motor deficits. At the right time, with the right cues, the brain can repair itself.

    更新日期:2017-09-26
  • Choosing the right bar: a complex problem
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Mai M Morimoto, Aman B Saleem

    Choosing the right bar: a complex problem Nature Neuroscience, Published online: 26 September 2017; doi:10.1038/nn.4646 Inputs to the central complex, the navigation center of Drosophila, are strongly modulated by the visual stimulus history. These history effects carry forward to bias turning behavior when flies choose between two visual stimuli.

    更新日期:2017-09-26
  • Corrigendum: L1-associated genomic regions are deleted in somatic cells of the healthy human brain
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Jennifer A Erwin, Apuã C M Paquola, Tatjana Singer, Iryna Gallina, Mark Novotny, Carolina Quayle, Tracy A Bedrosian, Francisco I A Alves, Cheyenne R Butcher, Joseph R Herdy, Anindita Sarkar, Roger S Lasken, Alysson R Muotri, Fred H Gage

    Corrigendum: L1-associated genomic regions are deleted in somatic cells of the healthy human brain Nature Neuroscience, Published online: 26 September 2017; doi:10.1038/nn1017-1427a

    更新日期:2017-09-26
  • Corrigendum: Hormonal gain control of a medial preoptic area social reward circuit
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Jenna A McHenry, James M Otis, Mark A Rossi, J Elliott Robinson, Oksana Kosyk, Noah W Miller, Zoe A McElligott, Evgeny A Budygin, David R Rubinow, Garret D Stuber

    Corrigendum: Hormonal gain control of a medial preoptic area social reward circuit Nature Neuroscience, Published online: 26 September 2017; doi:10.1038/nn1017-1427c

    更新日期:2017-09-26
  • Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Yvonne Schwarz, Na Zhao, Frank Kirchhoff, Dieter Bruns

    Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic vesicles and neuropeptide Y-containing large dense-core vesicles, respectively. Using individual null-mutants for Vamp2 (synaptobrevin II) and Vamp3 (cellubrevin), as well as the corresponding compound null-mutant for genes encoding both v-SNARE proteins, we delineate previously unrecognized individual v-SNARE dependencies of astrocytic release processes and their functional impact on neuronal signaling. Specifically, we show that astroglial cellubrevin-dependent neuropeptide Y secretion diminishes synaptic signaling, while synaptobrevin II–dependent glutamate release from astrocytes enhances synaptic signaling. Our experiments thereby uncover the molecular mechanisms of two distinct v-SNARE-dependent astrocytic release pathways that oppositely control synaptic strength at presynaptic sites, elucidating new avenues of communication between astrocytes and neurons.

    更新日期:2017-09-25
  • Synapse-specific astrocyte gating of amygdala-related behavior
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Mario Martin-Fernandez, Stephanie Jamison, Laurie M Robin, Zhe Zhao, Eduardo D Martin, Juan Aguilar, Michael A Benneyworth, Giovanni Marsicano, Alfonso Araque

    The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.

    更新日期:2017-09-25
  • α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Diana G Ferreira, Mariana Temido-Ferreira, Hugo Vicente Miranda, Vânia L Batalha, Joana E Coelho, Éva M Szegö, Inês Marques-Morgado, Sandra H Vaz, Jeong Seop Rhee, Matthias Schmitz, Inga Zerr, Luísa V Lopes, Tiago F Outeiro

    Synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders that are characterized by the accumulation of α-synuclein (aSyn) in intracellular inclusions known as Lewy bodies. Prefibrillar soluble aSyn oligomers, rather than larger inclusions, are currently considered to be crucial species underlying synaptic dysfunction. We identified the cellular prion protein (PrPC) as a key mediator in aSyn-induced synaptic impairment. The aSyn-associated impairment of long-term potentiation was blocked in Prnp null mice and rescued following PrPC blockade. We found that extracellular aSyn oligomers formed a complex with PrPC that induced the phosphorylation of Fyn kinase via metabotropic glutamate receptors 5 (mGluR5). aSyn engagement of PrPC and Fyn activated NMDA receptor (NMDAR) and altered calcium homeostasis. Blockade of mGluR5-evoked phosphorylation of NMDAR in aSyn transgenic mice rescued synaptic and cognitive deficits, supporting the hypothesis that a receptor-mediated mechanism, independent of pore formation and membrane leakage, is sufficient to trigger early synaptic damage induced by extracellular aSyn.

    更新日期:2017-09-25
  • Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex
    Nat. Neurosci. (IF 17.839) Pub Date : 2017-09-18
    Harald Prüss, Andrea Tedeschi, Aude Thiriot, Lydia Lynch, Scott M Loughhead, Susanne Stutte, Irina B Mazo, Marcel A Kopp, Benedikt Brommer, Christian Blex, Laura-Christin Geurtz, Thomas Liebscher, Andreas Niedeggen, Ulrich Dirnagl, Frank Bradke, Magdalena S Volz, Michael J DeVivo, Yuying Chen, Ulrich H von Andrian, Jan M Schwab

    Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus–pituitary–adrenal axis stimulation. Instead of consecutive hypothalamus–pituitary–adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism. This neurogenic effect was more pronounced after high-thoracic level (Th1) SCI disconnecting adrenal gland innervation, compared with low-thoracic level (Th9) SCI. Prophylactic adrenalectomy completely prevented SCI-induced glucocorticoid excess and lymphocyte depletion but did not prevent pneumonia. When adrenalectomized mice were transplanted with denervated adrenal glands to restore physiologic glucocorticoid levels, the animals were completely protected from pneumonia. These findings identify a maladaptive sympathetic-neuroendocrine adrenal reflex mediating immunosuppression after SCI, implying that therapeutic normalization of the glucocorticoid and catecholamine imbalance in SCI patients could be a strategy to prevent detrimental infections.

    更新日期:2017-09-20
  • Esr1+ cells in the ventromedial hypothalamus control female aggression
    Nat. Neurosci. (IF 17.839) Pub Date : 
    Koichi Hashikawa, Yoshiko Hashikawa, Robin Tremblay, Jiaxing Zhang, James E Feng, Alexander Sabol, Walter T Piper, Hyosang Lee, Bernardo Rudy, Dayu Lin

    As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvlEsr1+ cells are indispensable for female aggression. This population was active when females attacked naturally. Inactivation of these cells reduced female aggression whereas their activation elicited attack. Additionally, we found that female VMHvl contains two anatomically distinguishable subdivisions that showed differential gene expression, projection and activation patterns after mating and fighting. These results support an essential role of the VMHvl in both male and female aggression and reveal the existence of two previously unappreciated subdivisions in the female VMHvl that are involved in distinct social behaviors.

    更新日期:2017-09-19
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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