Nature Neuroscience Contents: March 2015 Volume 18 Number 3, pp 317 - 475

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Advertisement Conquer Paralysis Now is offering 12 grants of at least $50,000 in 6 categories for research related to Spinal Cord Injury (SCI) treatments. The deadline to apply is April 1, 2015. See the challenge for more information. TABLE OF CONTENTS March 2015 Volume 18, Issue 3 Focus Editorial Obituary Correspondence News and Views Perspectives Reviews Brief Communications Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement The New York Stem Cell Foundation - Robertson Investigator Awards in Neuroscience NYSCF is now accepting applications from early career investigators who are working on high-risk, high-reward science in the areas of developmental, cellular, cognitive and behavioral neuroscience. Awards provide $1.5M over 5 years. Deadline: March 18, 2015. View the RFA: www.nyscf.org/neuro   Advertisement Nature Genetics, Central South University, and Anhui Medical University present:  Genome Variation in Precision Medicine 2015 May 17-19, 2015 | Changsha, China Register Now!    Focus Top Focus on epilepsy Focus issue: March 2015 Volume 18, No 3 Contents Editorial Perspectives Reviews Editorial Top Focus on epilepsy   p317 doi:10.1038/nn.3964 Nature Neuroscience presents a Focus issue highlighting recent advances in elucidating the mechanisms driving the onset and persistence of the epilepsies. Obituary Top Vernon B. Mountcastle 1918-2015   p318 Solomon H Snyder doi:10.1038/nn.3958 Correspondence Top GDNF is not required for catecholaminergic neuron survival in vivo   pp319 - 322 Jaakko Kopra, Carolina Vilenius, Shane Grealish, Mari-Anne Härma, Kärt Varendi et al. doi:10.1038/nn.3941 Glial cell line-derived neurotrophic factor (GDNF) is in clinical trials for treating Parkinson's disease. However, endogenous GDNF function in brain catecholaminergic neurons has remained controversial. The authors utilized three complementary conditional knock-out approaches during development and adulthood and found that GDNF is not required for the maintenance of the catecholaminergic neurons in mice. Reply to “GDNF is not required for catecholaminergic neuron survival in vivo”   pp322 - 323 Alberto Pascual and José López-Barneo doi:10.1038/nn.3942 News and Views Top The amygdala accountant: new tricks for an old structure   pp324 - 325 Clayton P Mosher and Peter H Rudebeck doi:10.1038/nn.3949 What drives us to pursue distant, more valuable goals over more proximate, lesser ones? Counter to what you might expect, this type of advanced goal-directed planning and foresight in primates may involve the amygdala. In a reward savings task, neurons in the amygdala track the length and subjective value of internally generated plans. See also: Article by Hernadi et al. Neighborly synapses help each other out   pp326 - 327 J Simon Wiegert and Thomas G Oertner doi:10.1038/nn.3955 Cortical circuits are shaped by sensory experience. These changes have now been visualized with single-synapse resolution in vivo, revealing clustered potentiation along stretches of dendrite. See also: Article by Zhang et al. Attention: feedback focuses a wandering mind   pp327 - 328 Edward Awh and Edward K Vogel doi:10.1038/nn.3962 Neurofeedback that tracks attentional focus in real time using fMRI and alerts subjects to impending lapses by modulating the difficulty of the task itself has been demonstrated to improve behavioral performance. See also: Article by deBettencourt et al. Tread softly and carry a clock's tick   pp329 - 330 Joseph J Paton and Brian Lau doi:10.1038/nn.3959 Skilled behavior is thought to rely on the dorsal striatum. A study now reports that skills depend on striatal encoding of movement kinematics, linking learned sequences of movements with temporally distributed striatal activity. See also: Article by Rueda-Orozco & Robbe Neuroscience JOBS of the week Two post-doctoral fellow positions in Neuroscience available Burke Medical Research Institute Postdoc in Drug Delivery University of North Texas Health Science Center at Fort Worth Cognitive Neuroscience Research Assistant Stanford University Tenure Stream Positions in the Neurobiology of Dementia University of Pittsburgh Brain Institute and Department of Neurobiology Assistant or Associate Professor Stanford University Department of Comparative Medicine More Science jobs from Neuroscience EVENT British Association for Cognitive Neuroscience Annual Scientific Meeting, Essex 2015 10 September 15 University of Essex More science events from Perspectives Top Beyond the hammer and the scalpel: selective circuit control for the epilepsies   pp331 - 338 Esther Krook-Magnuson and Ivan Soltesz doi:10.1038/nn.3943 Current treatment options are, for many patients with epilepsy, either insufficient or ineffective and, thus, new therapeutic methodologies are necessary. In this Perspective, Esther Krook-Magnuson and Ivan Soltesz look at recent advances in optogenetic-based modulation of circuit activity and seizures with an eye toward the prospect—and challenges—of utilizing these technologies for the treatment of epilepsy. Animal models in epilepsy research: legacies and new directions   pp339 - 343 Brian P Grone and Scott C Baraban doi:10.1038/nn.3934 In this Perspective article, Brian Grone and Scott Baraban examine some of the numerous nonhuman animal models of epilepsy. The authors outline how traditional animal models have advanced our understanding of seizure initiation and epileptogenesis and also describe how the use of more 'non-traditional' model systems may further improve insight into both disease mechanisms as well as potential therapeutic avenues. Reviews Top Pathway-driven discovery of epilepsy genes   pp344 - 350 Jeffrey Noebels doi:10.1038/nn.3933 In this Review, Jeff Noebels examines recent advances in the identification of new genes underlying the onset of epilepsy. Given their functional convergence on synaptic inhibition and rich interactive landscape, collective analysis of genes driving major network interactions—as performed in the cancer field—may help point the way forward toward better diagnostics and target prioritization. Microcircuits and their interactions in epilepsy: is the focus out of focus?   pp351 - 359 Jeanne T Paz and John R Huguenard doi:10.1038/nn.3950 In this Review, Jeanne Paz and John Huguenard examine how recent work has informed us on the function of brain microcircuitry and how different circuit types may contribute to seizure generation and/or propagation. The authors also propose the idea that these microcircuits may regulate the spread of seizures and represent new targets for therapeutic intervention. Reprogramming patient-derived cells to study the epilepsies   pp360 - 366 Jack M Parent and Stewart A Anderson doi:10.1038/nn.3944 In this Review article, Jack Parent and Stewart Anderson discuss the advantages and limitations of using patient-derived cells, such as induced pluripotent stem cells, to probe the mechanisms of epileptogenesis and disease progression. In addition, they look at potential therapeutic avenues, such as cell-replacement strategies, that may arise from this field. Molecular mechanisms of epilepsy   pp367 - 372 Kevin Staley doi:10.1038/nn.3947 The term /`seizure/' emphasizes the abrupt and unpredictable nature of the onset of epochs of pathological neuronal synchrony that define the disorder of epilepsy. Mechanisms of epilepsy should account for seizure transitions with these unique temporal properties. In this review, Kevin Staley discusses how combining insights from new genetic etiologies with seizure timing may begin to outline the mechanisms by which the brain becomes predisposed to seizures. Brief Communications Top Manipulating circadian clock neuron firing rate resets molecular circadian rhythms and behavior   pp373 - 375 Jeff R Jones, Michael C Tackenberg and Douglas G McMahon doi:10.1038/nn.3937 Using optogenetic manipulations and bioluminescence imaging of suprachiasmatic nucleus (SCN) firing rate, this study examines the interaction between molecular, electrical and behavioral circadian rhythms in mice. The study shows that alteration of clock neuron firing can reset molecular and behavioral circadian rhythms, and this effect required neuronal network interaction within the SCN. Thus, clock neuron spiking is fundamental to circadian pacemaking as both an input to and output of the neuronal network responsible for circadian behavior. Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula   pp376 - 378 Frank J Meye, Kristina Valentinova, Salvatore Lecca, Lucile Marion-Poll, Matthieu J Maroteaux et al. doi:10.1038/nn.3923 This study shows that cocaine strengthens glutamatergic transmission, reduces K+ channel function and drives hyperexcitability in lateral habenula neurons projecting to the rostromedial tegmental nucleus. The authors also show that GluA1 trafficking mediates these cellular modifications and is instrumental in a drug-mediated depressive-like phenotype. Articles Top A neuroprotective role for microRNA miR-1000 mediated by limiting glutamate excitotoxicity   pp379 - 385 Pushpa Verma, George J Augustine, Mohamed-Raafet Ammar, Ayumu Tashiro and Stephen M Cohen doi:10.1038/nn.3935 microRNAs control synaptic signaling through regulation of postsynaptic responsiveness. This study provides evidence that the conserved microRNAs miR-1000 and miR-137 act presynaptically via glutamate transporters to regulate glutamate release. miR-1000 expression is activity dependent, perhaps allowing activity to fine-tune the strength of excitatory synaptic transmission. Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons   pp386 - 392 Shiliang Zhang, Jia Qi, Xueping Li, Hui-Ling Wang, Jonathan P Britt et al. doi:10.1038/nn.3945 Dopamine axons projecting from the ventral tegmental area to the nucleus accumbens (mesoaccumbens axons) play a role in motivation. Tthe authors show that there are distinct microdomains releasing either dopamine or glutamate within individual mesoaccumbens axons in rats and mice. Sensory inputs control the integration of neurogliaform interneurons into cortical circuits   pp393 - 401 Natalia V De Marco Garcia, Rashi Priya, Sebnem N Tuncdemir, Gord Fishell and Theofanis Karayannis doi:10.1038/nn.3946 Neurogliaform interneurons constitute an essential component of cortical circuits. This paper provides evidence that, during early development, superficial neurogliaform cells of the primary somatosensory barrel field cortex receive prominent innervation from the thalamus. These afferents also activate postsynaptic NR2B-containing NMDA receptors, which are essential for the neurons' proper cortical integration. Visualization of NMDA receptor-dependent AMPA receptor synaptic plasticity in vivo   pp402 - 407 Yong Zhang, Robert H Cudmore, Da-Ting Lin, David J Linden and Richard L Huganir doi:10.1038/nn.3936 Insertion of AMPA receptors into the synaptic membrane is thought to be a central mechanism for controlling experience-dependent changes in synaptic strength, yet this has never been observed in real time in the intact brain. Using two-photon imaging, Zhang and colleagues were able to provide this missing piece of information by tracking the insertion of GluA1 in spines in mouse barrel cortex neurons during repetitive whisker stimulation. See also: News and Views by Wiegert & Oertner Optogenetic perturbation of preBotzinger complex inhibitory neurons modulates respiratory pattern   pp408 - 414 David Sherman, Jason W Worrell, Yan Cui and Jack L Feldman doi:10.1038/nn.3938 The authors investigated the role of glycinergic preBotC neurons in respiratory rhythmogenesis in mice using viral delivery of Channelrhodopsin-2 (ChR2) or Archaerhodopsin (Arch) genes. They conclude that glycinergic preBotC neurons modulate inspiratory pattern and are important for reflex apneas but that the rhythm can persist after significant dampening of their activity. Epigenetic basis of opiate suppression of Bdnf gene expression in the ventral tegmental area   pp415 - 422 Ja Wook Koo, Michelle S Mazei-Robison, Quincey LaPlant, Gabor Egervari, Kevin M Braunscheidel et al. doi:10.1038/nn.3932 Comprehensive analysis of epigenetic regulation demonstrates a series of complex, interacting chromatin mechanisms by which chronic exposure to opiates downregulates Bdnf gene transcription in the ventral tegmental area. This regulatory cascade is also shown to play a role in controlling opiate-induced behavioral plasticity. Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory   pp423 - 434 Anna G Orr, Edward C Hsiao, Max M Wang, Kaitlyn Ho, Daniel H Kim et al. doi:10.1038/nn.3930 The authors show that astrocytes produce high levels of the adenosine receptor A2A in Alzheimer brains. Reducing the levels of astrocytic A2A boosted memory in young and aging mice and mouse models of Alzheimer disease, whereas activating a related molecular pathway impaired memory. Thus, astrocytes regulate memory and abnormal receptor activity in these cells may contribute to memory disorders. Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression   pp435 - 443 Woosuk Chung, Su Yeon Choi, Eunee Lee, Haram Park, Jaeseung Kang et al. doi:10.1038/nn.3927 Enhanced NMDA receptor function and social interaction deficits are observed in mice lacking the excitatory postsynaptic scaffolding protein IRSp53. Reducing NMDAR activity by pharmacological methods rescues the impaired social interaction observed in these mice. This suggests that enhanced NMDA receptor function may be associated with social deficits. In vivo coincidence detection in mammalian sound localization generates phase delays   pp444 - 452 Tom P Franken, Michael T Roberts, Liting Wei, Nace L Golding and Philip X Joris doi:10.1038/nn.3948 Coincidence detection is a fundamental neural operation, developed to an extreme in the computation of interaural time differences for sound localization. This study utilizes intracellular in vivo recordings and pharmacological manipulations in the medial superior olive of Mongolian gerbil to reveal that maximal coincidence is not just determined by the timing of synaptic inputs, but also by intrinsic neural properties. The striatum multiplexes contextual and kinematic information to constrain motor habits execution   pp453 - 460 Pavel E Rueda-Orozco and David Robbe doi:10.1038/nn.3924 The authors recorded spiking activity in the sensorimotor striatum of rats performing a motor sequence in an automatic manner. They report continuous and integrative representation of contextual and kinematic information. Reversible perturbation of these representation increased execution variability, suggesting a strong contribution in constraining the execution motor habits. See also: News and Views by Paton & Lau Planning activity for internally generated reward goals in monkey amygdala neurons   pp461 - 469 István Hernádi, Fabian Grabenhorst and Wolfram Schultz doi:10.1038/nn.3925 Combining single-neuron recordings and a multistep economic choice task in monkeys, the authors find activity in amygdala neurons that predicts the value and length of an internally planned choice sequence leading to future reward. Prospective amygdala activity appears to encode components of an internal plan and guide behavior over several steps towards self-defined, distant goals. See also: News and Views by Mosher & Rudebeck Closed-loop training of attention with real-time brain imaging   pp470 - 475 Megan T deBettencourt, Jonathan D Cohen, Ray F Lee, Kenneth A Norman and Nicholas B Turk-Browne doi:10.1038/nn.3940 Lapses of attention are commonplace, potentially because they are detected too late to be prevented. The authors use real-time fMRI to provide participants continuous access to their attentional state. Real-time feedback, particularly from frontoparietal cortex, improved sustained attention abilities and modified representations in visual cortex and basal ganglia. See also: News and Views by Awh & Vogel Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. 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