|  | |  |  | | Advertisement |  | | |  | | | Focus | Top |  |  |  |  | | Focus on Neurotechniques |  | Focus issue: July 2013 Volume 16, No 7 | | Editorial | Top |  |  |  | Focus on neurotechniques p771 doi:10.1038/nn0713-771 Nature Neuroscience presents a focus highlighting recent technical advances in neuroscience. |  | News and Views | Top |  |  |  | |  | Reviews | Top |  |  |  | Opportunities and challenges of pluripotent stem cell neurodegenerative disease models pp780 - 789 Jackson Sandoe and Kevin Eggan doi:10.1038/nn.3425 The use of patient-derived stem cells for in vitro neurodegenerative disease modeling has gained much traction in recent years. In this review, the authors examine the potential caveats and pitfalls of stem cell use and highlight insights from the literature that suggest methods for overcoming these difficulties. |  |  |  | Seeing the forest tree by tree: super-resolution light microscopy meets the neurosciences pp790 - 797 Marta Maglione and Stephan J Sigrist doi:10.1038/nn.3403 Standard light microscopy techniques cannot resolve the subcellular structures of neurons: axons, presynaptic active zones, postsynaptic densities and dendritic spines. In this review, the authors discuss the use of recently developed super-resolution light microscopic techniques to resolve these structures, and how such techniques can be most effectively used in the future. |  |  |  | Immunogold cytochemistry in neuroscience pp798 - 804 Mahmood Amiry-Moghaddam and Ole Petter Ottersen doi:10.1038/nn.3418 Immunogold techniques allow target proteins to be localized subcellularly quantitatively and with high precision. In this review, the authors discuss applications of these techniques, as well as limitations and possible pitfalls to be avoided in their use. |  |  |  | Targeting neurons and photons for optogenetics pp805 - 815 Adam M Packer, Botond Roska and Michael Häusser doi:10.1038/nn.3427 The strength and versatility of optogenetics rely not only on the diversity of the optogene toolkit but also on the ability to achieve spatially selective and temporally precise control of electrical activity in specific neural circuits, individual cells or subcellular compartments. This remains a challenge and requires sophisticated experimental designs. In this article, Packer, Roska and Hausser discuss the myriad combinations of optical, anatomical and genetic strategies that can be used to manipulate neuronal activity with light. |  |  |  | Optogenetic pharmacology for control of native neuronal signaling proteins pp816 - 823 Richard H Kramer, Alexandre Mourot and Hillel Adesnik doi:10.1038/nn.3424 This review discusses recent advances in optogenetic pharmacology, discussing its potential to manipulate endogenous neuronal signaling proteins. These approaches include caged agonists and antagonists and reversibly photoswitchable ligands. |  |  |  | Probing perceptual decisions in rodents pp824 - 831 Matteo Carandini and Anne K Churchland doi:10.1038/nn.3410 In this review article, the authors give a brief overview of the sensory capabilities of rodents and of their cortical areas devoted to sensation and decision. They also review methods of psychophysics, focusing on the technical issues that arise in their implementation in rodents. |  |  |  | Opportunities and limitations of intrinsic functional connectivity MRI pp832 - 837 Randy L Buckner, Fenna M Krienen and B T Thomas Yeo doi:10.1038/nn.3423 The authors review recent work using functional connectivity in fMRI and discuss the issues that constrain the interpretation of these studies, as well as the potential uses of this analysis technique. |  |  |  | Noninvasive brain stimulation: from physiology to network dynamics and back pp838 - 844 Eran Dayan, Nitzan Censor, Ethan R Buch, Marco Sandrini and Leonardo G Cohen doi:10.1038/nn.3422 The authors provide an overview of the uses and limitations of noninvasive brain stimulation techniques such as transcranial magnetic stimulation and suggest ways to advance the field. |  | Brief Communications | Top |  |  |  | Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume pp845 - 847 Grégory Conductier, Frédéric Brau, Angèle Viola, Fanny Langlet, Navean Ramkumar, Bénédicte Dehouck, Thibault Lemaire, Raphaël Chapot, Laurianne Lucas, Carole Rovère, Priscilla Maitre, Salma Hosseiny, Agnès Petit-Paitel, Antoine Adamantidis, Bernard Lakaye, Pierre-Yves Risold, Vincent Prévot, Olivier Meste, Jean-Louis Nahon & Alice Guyon doi:10.1038/nn.3401 Ependymal cell cilia regulate cerebrospinal fluid flow through the cerebral ventricles. Here the authors show that the metabolic peptide melanin-concentrating hormone (MCH) increases cilia beat frequency in the third ventricle, and a lack of the MCH receptor increases ventricle size. |  |  |  | CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology pp848 - 850 Elizabeth M Bradshaw, Lori B Chibnik, Brendan T Keenan, Linda Ottoboni, Towfique Raj, Anna Tang, Laura L Rosenkrantz, Selina Imboywa, Michelle Lee, Alina Von Korff, The Alzheimer Disease Neuroimaging Initiative, Martha C Morris, Denis A Evans, Keith Johnson, Reisa A Sperling, Julie A Schneider, David A Bennett & Philip L De Jager doi:10.1038/nn.3435 Genome-wide association studies have identified CD33 as an Alzheimer's disease susceptibility locus. Here, the authors show that the CD33 risk allele is associated with altered myeloid function, microglial activation and in vivo amyloid pathology. |  | Articles | Top |  |  |  | Exome sequencing to identify de novo mutations in sporadic ALS trios pp851 - 855 Alessandra Chesi, Brett T Staahl, Ana Jovičić, Julien Couthouis, Maria Fasolino, Alya R Raphael, Tomohiro Yamazaki, Laura Elias, Meraida Polak, Crystal Kelly, Kelly L Williams, Jennifer A Fifita, Nicholas J Maragakis, Garth A Nicholson, Oliver D King, Robin Reed, Gerald R Crabtree, Ian P Blair, Jonathan D Glass & Aaron D Gitler doi:10.1038/nn.3412 Exome sequencing of 47 ALS trios (patients and their unaffected parents) identified de novo mutations, including a mutation in the neuronal chromatin remodeling complex component, SS18L1. SS18L1 interacted with the ALS protein FUS, and mutation of SS18L1 in primary neurons resulted in impaired neurite outgrowth.
See also: News and Views by Renton & Traynor |  |  |  | BMP signaling specifies the development of a large and fast CNS synapse pp856 - 864 Le Xiao, Nicolas Michalski, Elin Kronander, Enida Gjoni, Christel Genoud, Graham Knott & Ralf Schneggenburger doi:10.1038/nn.3414 The calyx of Held synapse in the auditory brainstem is an unusually large and fast synapse. Using genome-wide screening and conditional deletion in mice, Xiao and colleagues identify BMP signaling as a crucial factor in the development of the functional and structural properties of this large central synapse. |  |  |  | TNFα reverse signaling promotes sympathetic axon growth and target innervation pp865 - 873 Lilian Kisiswa, Catarina Osório, Clara Erice, Thomas Vizard, Sean Wyatt & Alun M Davies doi:10.1038/nn.3430 The authors show that the TNFα receptor, expressed on peripheral target tissue, can act as a ligand to induce reverse TNFα signaling in superior cervical ganglion neurons, promoting neurite growth and branching. This reverse signaling is crucial in establishing sympathetic innervation. |  |  |  | Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity pp874 - 883 Erica Korb, Carol L Wilkinson, Ryan N Delgado, Kathryn L Lovero and Steven Finkbeiner doi:10.1038/nn.3429 In this paper, Korb and colleagues find that Arc can shuttle in and out of the nucleus in an activity-dependent manner. The authors further demonstrate that the nuclear translocation of Arc participates in homeostatic plasticity by promoting the formation of PML nuclear bodies, which in turn decreases GluA1 transcription, eventually contributing to the downscaling of synaptic strength. |  |  |  | Interhemispheric asymmetry of olfactory input-dependent neuronal specification in the adult brain pp884 - 888 Norihito Kishimoto, Kazuhide Asakawa, Romain Madelaine, Patrick Blader, Koichi Kawakami & Kazunobu Sawamoto doi:10.1038/nn.3409 The authors identify a hemispheric asymmetry in neurogenesis in adult zebrafish. This asymmetry could be reversed by olfactory sensory deprivation or decreasing Notch signaling on the left side. Behavioral responses of fish to olfactory cues depended on the left olfactory epithelium, which may be a result of this asymmetry in neurogenesis. |  |  |  | The cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow pp889 - 897 Pablo Blinder, Philbert S Tsai, John P Kaufhold, Per M Knutsen, Harry Suhl & David Kleinfeld doi:10.1038/nn.3426 The authors use high-throughput histology to construct three-dimensional maps of the vascular architecture throughout mouse vibrissal cortex. Modeling of the vascular networks revealed that microvessels are highly interconnected; do not form functional 'modules', as previously suggested; and lead to flow patterns that explain the origin of single vessel strokes. |  |  |  | Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor pp898 - 902 Matthew J Lyst, Robert Ekiert, Daniel H Ebert, Cara Merusi, Jakub Nowak, Jim Selfridge, Jacky Guy, Nathaniel R Kastan, Nathaniel D Robinson, Flavia de Lima Alves, Juri Rappsilber, Michael E Greenberg & Adrian Bird doi:10.1038/nn.3434 In this study, the authors show that MeCP2 interacts with the NCoR/SMRT co-repressor complex and that a discrete cluster of Rett syndrome-causing mutations in the C-terminal domain of MeCP2 disrupts this interaction, impairing transcriptional repression. Knock-in mice expressing one of these MeCP2 missense mutations exhibit severe motor phenotypes. |  |  |  | Circuit level defects in the developing neocortex of Fragile X mice pp903 - 909 J Tiago Gonçalves, James E Anstey, Peyman Golshani and Carlos Portera-Cailliau doi:10.1038/nn.3415 The authors use two-photon calcium imaging, EEG and electrophysiology to study ensemble neuronal activity in genetically altered mice that lack the Fmr1 protein: a model of Fragile X syndrome. Unanesthetized Fmr1-/- mice showed high synchrony of neocortical network activity and higher firing rates during sleep. |  |  |  | Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons pp910 - 918 David P Roberson, Sagi Gudes, Jared M Sprague, Haley A W Patoski, Victoria K Robson, Felix Blasl, Bo Duan, Seog Bae Oh, Bruce P Bean, Qiufu Ma, Alexander M Binshtok & Clifford J Woolf doi:10.1038/nn.3404 In this study, the authors use selective silencing of specific subsets of afferent neurons and stimulation with pruritogens or algogens to show that histaminergic and non-histaminergic itch is mediated by functionally distinct sets of sensory fibers. These findings provide further evidence for the labeled line theory of sensory perception.
See also: News and Views by Wilson & Bautista |  |  |  | Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles pp919 - 924 Hui Wang, Florian Duclot, Yan Liu, Zuoxin Wang and Mohamed Kabbaj doi:10.1038/nn.3420 The authors show that mating-induced partner preference in monogamous prairie voles is associated with increased histone acetylation at the oxytocin and vasopressin V1a receptor promoters, and subsequent upregulation of these genes. Histone deacetylase inhibitors induced partner preference in females even in the absence of mating.
See also: News and Views by Gundersen |  |  |  | Robust timing and motor patterns by taming chaos in recurrent neural networks pp925 - 933 Rodrigo Laje and Dean V Buonomano doi:10.1038/nn.3405 Here the authors describe a recurrent neural network model that tells time on the order of seconds and generates complex spatiotemporal motor patterns in the presence of high levels of noise. Robustness is achieved through the tuning of the recurrent connections, which produces stable patterns in the face of perturbations.
See also: News and Views by Renart |  |  |  | Synaptic mechanisms of adaptation and sensitization in the retina pp934 - 941 Anton Nikolaev, Kin-Mei Leung, Benjamin Odermatt and Leon Lagnado doi:10.1038/nn.3408 Imaging calcium and vesicular release from thousands of synapses during contrast adaptation, Nikolaev and colleagues reveal the stratified organization of depressing and facilitating bipolar cells terminals in the zebrafish retina. The study also offers some insights into the cellular and circuit mechanisms of bidirectional gain modulation in this sensory system. |  |  |  | Temporal whitening by power-law adaptation in neocortical neurons pp942 - 948 Christian Pozzorini, Richard Naud, Skander Mensi and Wulfram Gerstner doi:10.1038/nn.3431 Using a combination of computational modeling and electrophysiological recordings, the authors show that the dynamics of spike-frequency adaptation have the effect of temporally decorrelating incoming signals. This decorrelation makes for more energy-efficient information transfer in the CNS. |  |  |  | Olfactory cortical neurons read out a relative time code in the olfactory bulb pp949 - 957 Rafi Haddad, Anne Lanjuin, Linda Madisen, Hongkui Zeng, Venkatesh N Murthy & Naoshige Uchida doi:10.1038/nn.3407 Odors evoke complex spatiotemporal patterns of activity in the olfactory bulb. The authors show that the spike rates of downstream piriform cortex neurons (PCNs) reflect the relative timing of activation. Posterior PCNs are more sensitive to input timing than anterior PCNs. |  |  |  | Neural coding during active somatosensation revealed using illusory touch pp958 - 965 Daniel H O'Connor, S Andrew Hires, Zengcai V Guo, Nuo Li, Jianing Yu, Qian-Quan Sun, Daniel Huber & Karel Svoboda doi:10.1038/nn.3419 The authors use mouse behavior, electrophysiology and optogenetics to dissect the temporal interactions between whisker movement, neural activity and sensation of touch. Their results suggest that mice integrate coding of touch with movement over timescales of a whisking bout to produce perception of active touch. |  |  |  | A causal link between prediction errors, dopamine neurons and learning pp966 - 973 Elizabeth E Steinberg, Ronald Keiflin, Josiah R Boivin, Ilana B Witten, Karl Deisseroth & Patricia H Janak doi:10.1038/nn.3413 Unexpected rewards activate midbrain dopamine neurons, and this response is proposed to support learning by signaling discrepancies between actual and expected outcomes. Here the authors use optogenetic stimulation to demonstrate a causal role for temporally precise dopamine neuron signaling in cue-reward learning.
See also: News and Views by Schoenbaum et al. |  |  |  | A functional and perceptual signature of the second visual area in primates pp974 - 981 Jeremy Freeman, Corey M Ziemba, David J Heeger, Eero P Simoncelli and J Anthony Movshon doi:10.1038/nn.3402 The authors examined neuronal responses in V1 and V2 to synthetic texture stimuli that replicate higher-order statistical dependencies found in natural images. V2, but not V1, responded differentially to these textures, in both macaque (single neurons) and human (fMRI). Human detection of naturalistic structure in the same images was predicted by V2 responses, suggesting a role for V2 in representing natural image structure. |  | Top | | Advertisement |  | Nature Methods Focus on Mapping the Brain www.nature.com/nmeth/focus/brainmapping
Experts discuss the different technologies needed to obtain anatomical and functional brain maps across species, and discuss the importance of assembling these maps and what will be needed beyond them, to understand the functioning of the brain.
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