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Volume 18 Issue 6, June 2015

Garfield and colleagues demonstrate that melanocortin-4 receptor (MC4R)-expressing neurons of the paraventricular nucleus of the hypothalamus (PVH) are required for the bidirectional control of feeding and that they induce satiety associated with an appetitive state. The cover depicts a stylized immunofluorescence image of MC4R-expressing neurons in the PVH (as demarked by an MC4R-t2a-Cre reporter line). It symbolizes both the PVH as the 'heart' of the hypothalamic feeding circuitry and the positive emotional valence of the MC4R-driven satiety. Cover design and concept by Michael J. Krashes and Alastair S. Garfield.789863

Editorial

  • Animal rights extremists are threatening nonhuman primate research by harassing scientists. We cannot tolerate these tactics, and we must rally individual, institutional and governmental support to protect scientists.

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News & Views

  • The prefrontal cortex is known to influence dopamine release in the striatum–but how? New data in mice suggest that cortical spine density affects striatal dopamine release via monosynaptic control of dopamine neurons, tracing a chain of events from spine loss to antipsychotic-responsive psychomotor agitation.

    • Christoph Kellendonk
    • Joshua A Gordon
    News & Views
  • Activation of AgRP-expressing 'hunger' neurons promotes robust feeding. Recent studies reveal the valence, dynamics and neural circuits engaged by AgRP neurons.

    • Richard Palmiter
    News & Views
  • Observing the choices of others adds utility to the chosen option. The additional utility conferred by others' choices is encoded by the ventromedial prefrontal cortex and explains the idiosyncratic effects of social influence.

    • David V Smith
    • Mauricio R Delgado
    News & Views
  • A study finds the transcription factor Lmx1b to be necessary in adults for preventing degeneration of midbrain dopamine neurons and implicates it in lysosomal function and regulation in these neurons.

    • Ole Isacson
    News & Views
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Perspective

  • The amyloid cascade is perhaps the most dominant hypothesis in the field of Alzheimer's disease pathogenesis, but it is also one of the most controversial. Here we present two Perspective articles that argue both for and against the amyloid hypothesis. In this opinionated piece, Dr. Herrup challenges the Alzheimer's field to re-examine the complex biochemical, clinical and epidemiological evidence and reassess its over-reliance on this proposed pathogenic mechanism.

    • Karl Herrup
    Perspective
  • The amyloid cascade is perhaps the most dominant hypothesis in the field of Alzheimer's disease pathogenesis but it is also one of the most controversial. Here, we present two Perspective articles which argue both for and against the amyloid hypothesis. In this piece, Drs. Musiek and Holtzman argue that, despite sometimes conflicting data, there is ample evidence to suggest that Aβ accumulation is a key initiator of AD-related pathology and may act as a trigger of downstream effects such as tau aggregation.

    • Erik S Musiek
    • David M Holtzman
    Perspective
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Article

  • Huntington disease (HD) is an incurable neurodegenerative disease. A SNP in the huntingtin promoter impaired NF-κB binding and acted as a bidirectional modifier of disease onset. Presence of the SNP on the mutant allele associated with delayed age of onset, while the SNP on the wild-type HTT allele associated with accelerated age of onset. These findings have direct therapeutic implications.

    • Kristina Bečanović
    • Anne Nørremølle
    • Blair R Leavitt
    Article
  • In this study, the authors show that the RNA repair and splicing pathway regulates axon regeneration in the nervous system of Drosophila. Rtca, a RNA cyclase, is a potent inhibitor of CNS axon regeneration, whereas Archease, a RNA splicing cofactor, functions downstream of Rtca as a pro-regeneration factor. Together, they modify the splicing of Xbp1 in the regulation of axon regeneration.

    • Yuanquan Song
    • David Sretavan
    • Yuh Nung Jan
    Article
  • This study establishes a key role for the developmental transcription factors Lmx1a/b in the maintenance of midbrain dopamine neurons. The authors show that postmitotic ablation of Lmx1b in mice leads to cellular and functional abnormalities resembling Parkinson's disease, most notably in a dysfunction in the autophagic-lysosomal pathway that results in abnormal dopaminergic synaptic connections and neuronal degeneration.

    • Ariadna Laguna
    • Nicoletta Schintu
    • Thomas Perlmann
    Article
  • The cellular function of active DNA demethylation in neurons is not well understood. Here, Song and colleagues show that synaptic activity modulates Tet3 signaling, which in turn regulates glutamatergic synaptic transmission and synaptic scaling. Their work identifies Tet3 as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation.

    • Huimei Yu
    • Yijing Su
    • Hongjun Song
    Article
  • Rhythmic firing is an essential feature of neuronal circuits generating rhythmic movements. This study shows that this property depends on astrocytes in the trigeminal circuit underlying mastication, where rhythmogenesis relies on activation of a persistent sodium current. Astrocytes modulate this conductance by decreasing the extracellular calcium through release of the calcium-binding protein S100β. Blockade of S100β or inactivation of astrocytes impedes rhythmogenesis.

    • Philippe Morquette
    • Dorly Verdier
    • Arlette Kolta
    Article
  • Light controls animal circadian behavior by regulating gene expression in the circadian clock. Here, Cao et al. reports that a light-activated MAPK/MNK pathway leads to phosphorylation of the cap-binding protein eIF4E and promotes mRNA translation of the clock gene Period 1 and 2 to facilitate clock resetting.

    • Ruifeng Cao
    • Christos G Gkogkas
    • Nahum Sonenberg
    Article
  • Melanocortin 4 receptors (MC4Rs) are critical to the promotion of homeostatic satiety. The authors established paraventricular hypothalamus (PVH) MC4R-expressing neurons as a functional target for orexigenic arcuate nucleus agouti-related peptide–expressing neurons and identify an explicit PVH MC4R-expressing neuron to lateral parabrachial nucleus satiety-promoting circuit, the activation of which encodes positive valence in calorically depleted mice.

    • Alastair S Garfield
    • Chia Li
    • Bradford B Lowell
    Article
  • Midbrain ventral tegmental neurons project to prefrontal cortex (PFC) and modulate cognition. The authors discovered a mesocortical circuit that provides glutamatergic excitation of interneurons and inhibits pyramidal neurons in the PFC. Moreover, they identified the subset of dopaminergic progenitors that generates these mesocortical neurons. Loss of these progenitors results in the loss of the inhibitory circuit and increased perseverative behavior.

    • Anna Kabanova
    • Milan Pabst
    • Sandra Blaess
    Article
  • This study identifies a mechanism linking loss of Arp2/3 to the progressive formation of shaft excitatory synaptic contacts. This leads to enhanced cortical excitation, striatal hyperdopaminergia and antipsychotic-responsive psychomotor agitation. This illustrates how diverse pathologies may converge downstream of spine actin disturbances to drive psychomotor behaviors.

    • Il Hwan Kim
    • Mark A Rossi
    • Scott H Soderling
    Article
  • Cholinergic modulation of cortex powerfully influences information processing and brain states, causing robust desynchronization of local field potentials and strong decorrelation of responses between neurons. In this paper, the authors reveal a somatostatin-expressing inhibitory neuron-driven cortical circuit that mediates this change in the temporal structure of cortical dynamics.

    • Naiyan Chen
    • Hiroki Sugihara
    • Mriganka Sur
    Article
  • In order to better distinguish the neural processing of speech versus language, this study measured brain responses to foreign speech that was temporally scrambled to varying extents. Using this manipulation to highlight sensitivity to speech independent of linguistic structure, the authors identify a bilateral locus of speech analysis in the superior temporal sulcus.

    • Tobias Overath
    • Josh H McDermott
    • David Poeppel
    Article
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Technical Report

  • The authors developed a transcriptional reporter of intracellular Ca2+ and used it to monitor activity in Drosophila sensory and neuromodulatory neurons. They demonstrate that this tool can be used to manipulate neurons basis of their activity and report variants that can be adapted to report activity across a wide range.

    • Xiaojing J Gao
    • Olena Riabinina
    • Liqun Luo
    Technical Report
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Corrigendum

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Erratum

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Corrigendum

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