Nature Neuroscience Contents: September 2015 Volume 18 Number 9, pp 1191 - 1341

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Advertisement The Advanced Neuroscience Mouse Model Portfolio  A major challenge in neuroscience research and drug discovery is the lack of easy access to relevant animal models for use in screening drug candidates.  The Advanced Neuroscience Mouse Model Portfolio provides simplified access to models and services for the study of neuronal disease and signaling. Learn about extensive phenotyping data, and aging services to help accelerate research outcomes.  Learn More TABLE OF CONTENTS September 2015 Volume 18, Issue 9 Focus Editorial News and Views Overview Q&A Historical Commentary Brief Communications Articles Resource Technical Report Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement An open access journal dedicated to highlighting the most important scientific advances in Parkinson's disease research, spanning the motor and non-motor disorders of Parkinson's disease. Part of the Nature Partner Journals series, npj Parkinson's Disease is published in partnership with the Parkinson's Disease Foundation. Open for submissions: http://bit.ly/1uUh8YB   Focus Top ChR2: Anniversary Issue Focus issue: September 2015 Volume 18, No 9 Contents Editorial Overview Q&A Historical Commentary Web Collection Editorial Top ChR2 coming of age   p1191 doi:10.1038/nn.4103 10 years ago, channelrhodopsin-2 was expressed in neurons and shown to control their activity. In this issue, we consider how the field has developed since these early optogenetic experiments. News and Views Top How a fly escapes the reflex trap   pp1192 - 1194 Holger G Krapp doi:10.1038/nn.4097 Reflexes help us maintain a default posture and direction of locomotion. But what if we deliberately want to move differently? In Drosophila, the brain modifies a visually driven stabilization reflex to enable voluntary movements. See also: Article by Kim et al. GABA receptors in a state of fear   pp1194 - 1196 Andrew Holmes and Alon Chen doi:10.1038/nn.4098 Our internal states can color our memories just as powerfully as the external environment. A study finds that hippocampal GABAA receptors and associated microRNAs are important for generating state-dependent contextual fear memories. See also: Article by Jovasevic et al. The changing tree in Parkinson's disease   pp1196 - 1198 Paolo Calabresi and Massimiliano Di Filippo doi:10.1038/nn.4092 Dopamine loss in Parkinson's disease affects not only the basal ganglia, but also motor cortex, causing a surprising increase of spine turnover in the cortical dendritic tree and altering synaptic plasticity and memory retention. See also: Article by Guo et al. Character studies   pp1198 - 1199 Ming Hsu and Adrianna C Jenkins doi:10.1038/nn.4093 How do individuals attribute dispositional properties, or traits, to others? A study suggests that associative learning processes underlie aspects of trait learning at both neural and behavioral levels. See also: Brief Communication by Hackel et al. Neuroscience JOBS of the week Postdoctoral Position - Molecular and Clinical Neuroscience VIB Jefferson Scholars Foundation Endowed Professorship in Neuroscience University of Virginia Postdoctoral Fellow in Neuroscience University of Texas Health Science Center at San Antonio Postdoc Fellowships and PhD Scholarships in Neuroscience DANDRITE, Aarhus University Senior Lecturer / Associate Professor In Neuroscience Melbourne University More Science jobs from Neuroscience EVENT Neuroscience R&D Technologies Conference 03.12.15 Barcelona, Spain More science events from Overview Top Optogenetics and the future of neuroscience   pp1200 - 1201 Edward S Boyden doi:10.1038/nn.4094 Q&A Top Optogenetics: 10 years after ChR2 in neurons—views from the community   pp1202 - 1212 Antoine Adamantidis, Silvia Arber, Jaideep S Bains, Ernst Bamberg, Antonello Bonci et al. doi:10.1038/nn.4106 On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique. Historical Commentary Top Optogenetics: 10 years of microbial opsins in neuroscience   pp1213 - 1225 Karl Deisseroth doi:10.1038/nn.4091 Over the past decade, modern optogenetics has emerged from the convergence of developments in microbial opsin engineering, genetic methods for targeting, and optical strategies for light delivery. In this Historical Commentary, Karl Deisseroth reflects on the optogenetic landscape, from the important steps but slow progress in the beginning to the acceleration in discovery seen in recent years. Brief Communications Top Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS   pp1226 - 1229 Ana Jovičić, Jerome Mertens, Steven Boeynaems, Elke Bogaert, Noori Chai et al. doi:10.1038/nn.4085 C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. With unbiased screens in Saccharomyces cerevisiae, Jovicic et al. identified potent modifiers of toxicity of dipeptide repeat proteins produced by unconventional translation of the C9orf72 repeat expansions, pointing to nucleocytoplasmic transport impairments as potential disease mechanisms. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections   pp1230 - 1232 Yonatan M Kupchik, Robyn M Brown, Jasper A Heinsbroek, Mary Kay Lobo, Danielle J Schwartz et al. doi:10.1038/nn.4068 It is widely assumed that D1 and D2 dopamine receptor-expressing striatal neurons code for discrete pathways in the basal ganglia. Combining optogenetics and electrophysiology, the authors show that this output architecture does not apply to nucleus accumbens neurons. Current thinking attributing D1/D2 selectivity to accumbens projections thus should be reconsidered. Instrumental learning of traits versus rewards: dissociable neural correlates and effects on choice   pp1233 - 1235 Leor M Hackel, Bradley B Doll and David M Amodio doi:10.1038/nn.4080 Humans learn about people and objects through positive and negative experiences, yet they can look beyond rewards to encode trait-level attributes such as generosity. The authors show that neural activity and choices reflect feedback-based learning about rewards and traits of people and slot machines and that trait learning strongly drives decisions about new social interactions. See also: News and Views by Hsu & Jenkins Articles Top EAG2 potassium channel with evolutionarily conserved function as a brain tumor target   pp1236 - 1246 Xi Huang, Ye He, Adrian M Dubuc, Rintaro Hashizume, Wei Zhang et al. doi:10.1038/nn.4088 This study shows conserved EAG2 potassium channel function in brain tumorigenesis and metastasis, cooperation of different potassium channels for mitotic volume regulation, and EAG2 enrichment at the trailing edge for local volume regulation and cell motility. The authors identified the FDA-approved drug thioridazine as an EAG2 blocker of potential therapeutic value. Cellular evidence for efference copy in Drosophila visuomotor processing   pp1247 - 1255 Anmo J Kim, Jamie K Fitzgerald and Gaby Maimon doi:10.1038/nn.4083 The authors show that fruit flies briefly silence visual processing during voluntary flight turns, which likely helps flies to ignore the image of the world sweeping over the retina during such turns. See also: News and Views by Krapp LSD1n is an H4K20 demethylase regulating memory formation via transcriptional elongation control   pp1256 - 1264 Jianxun Wang, Francesca Telese, Yuliang Tan, Wenbo Li, Chunyu Jin et al. doi:10.1038/nn.4069 The authors show that the neuron-specific LSD1 variant (LSD1n) promotes transcription initiation and elongation in response to neuronal activity. LSD1n is essential for spatial learning and long-term memory formation. LSD1n exhibits novel substrate specificity for histone H4 K20 methylation. Watch an audio-visual summary of the paper here GABAergic mechanisms regulated by miR-33 encode state-dependent fear   pp1265 - 1271 Vladimir Jovasevic, Kevin A Corcoran, Katherine Leaderbrand, Naoki Yamawaki, Anita L Guedea et al. doi:10.1038/nn.4084 Some stress-related memories are state-dependent: they cannot be retrieved unless the brain is in the same state as during initial encoding. The authors show that hippocampal extrasynaptic GABAA receptors, regulated by miR-33, support state-dependent contextual fear conditioning by altering the processing of context memories within the extended hippocampal circuit. See also: News and Views by Holmes & Chen Naturalistic stimulation drives opposing heterosynaptic plasticity at two inputs to songbird cortex   pp1272 - 1280 W Hamish Mehaffey and Allison J Doupe doi:10.1038/nn.4078 This study examines how key inputs to a brain area vital for song production can interact cooperatively to change each other. The authors show that naturalistic stimulation patterns drive bidirectional in vitro plasticity in synaptic inputs to a song production area, and use this understanding to manipulate song plasticity in vivo. Determinants of different deep and superficial CA1 pyramidal cell dynamics during sharp-wave ripples   pp1281 - 1290 Manuel Valero, Elena Cid, Robert G Averkin, Juan Aguilar, Alberto Sanchez-Aguilera et al. doi:10.1038/nn.4074 Using a combination of electrophysiological and neurochemical techniques the authors report that deep and superficial CA1 pyramidal neurons behave differently during hippocampal sharp-wave ripples, with deep cells becoming hyperpolarized and superficial cells undergoing depolarization. The study also reveals some of the microcircuit mechanisms that underlie this spatiotemporal specialization, including the involvement of CA2 pyramidal cells and the role of perisomatic inhibition. Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome   pp1291 - 1298 Jonathan Witton, Ragunathan Padmashri, Larissa E Zinyuk, Victor I Popov, Igor Kraev et al. doi:10.1038/nn.4072 The authors report that the ultrastructure and plasticity of excitatory synapses connecting dentate gyrus and CA3 of the hippocampus are severely compromised in a transchromosomic mouse model of Down syndrome. These alterations are accompanied by unstable information coding by CA3 and CA1 place cells, which may contribute to aspects of impaired cognition in the disease. Dynamic rewiring of neural circuits in the motor cortex in mouse models of Parkinson's disease   pp1299 - 1309 Lili Guo, Huan Xiong, Jae-Ick Kim, Yu-Wei Wu, Rupa R Lalchandani et al. doi:10.1038/nn.4082 Using in vivo imaging, the authors explore how dopamine loss in Parkinson/'s disease mouse models affects synaptic plasticity in motor cortex. They find that dopamine D1 and D2 receptor signaling distinctly regulates dendritic spine dynamics and that dopamine loss results in atypical synaptic adaptations. These mechanisms may contribute to impaired motor performance in Parkinson's disease. See also: News and Views by Calabresi & Di Filippo Learning to expect the unexpected: rapid updating in primate cerebellum during voluntary self-motion   pp1310 - 1317 Jessica X Brooks, Jerome Carriot and Kathleen E Cullen doi:10.1038/nn.4077 By recording from cerebellar output neurons during motor learning, the authors provide direct evidence for an elegant computation requiring the comparison of predicted and actual sensory feedback to signal unexpected sensation. Their results suggest that rapid updating of the cerebellum's internal model enables the brain to learn to expect unexpected sensory input. Oscillatory dynamics coordinating human frontal networks in support of goal maintenance   pp1318 - 1324 Bradley Voytek, Andrew S Kayser, David Badre, David Fegen, Edward F Chang et al. doi:10.1038/nn.4071 Humans have a capacity for hierarchical cognitive control—the ability to simultaneously control immediate actions while holding more abstract goals in mind. The authors show that neural oscillations establish dynamic communication networks within the frontal cortex and that these oscillations coordinate local neural activity with increasing cognitive control. Resource Top Identification of neurodegenerative factors using translatome-regulatory network analysis   pp1325 - 1333 Lars Brichta, William Shin, Vernice Jackson-Lewis, Javier Blesa, Ee-Lynn Yap et al. doi:10.1038/nn.4070 To elucidate novel molecular mechanisms underlying neurodegeneration in Parkinson's disease, the authors generated mice for cell type-specific profiling of dopaminergic neurons. Regulatory network analysis of translatome libraries from dopaminergic neurons under degenerative stress facilitated the identification of intrinsic upstream regulators that oppose degeneration. This strategy can be generalized to investigate degeneration of other classes of neurons. Technical Report Top Cell type-specific manipulation with GFP-dependent Cre recombinase   pp1334 - 1341 Jonathan C Y Tang, Stephanie Rudolph, Onkar S Dhande, Victoria E Abraira, Seungwon Choi et al. doi:10.1038/nn.4081 GFP reporter lines are useful for labeling specific cell types. Here, the authors developed a method to convert GFP expression directly into Cre recombinase activity. GFP-dependent Cre was delivered via electroporation or AAV to neural tissues in the mouse, and could be used for optogenetic control of specific cell types. Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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