Nature Neuroscience Contents: February 2014 Volume 17 Number 2, pp 145 - 329

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Advertisement How the brain heals emotional wounds: the functional neuroanatomy of forgiveness (open access) In this article from Frontiers in Human Neuroscience, Pietro Pietrini and colleagues examined the brain correlates of forgiveness using functional Magnetic Resonance Imaging (fMRI). Healthy participants were induced to imagine social scenarios that described emotionally hurtful events followed by the indication to either forgive the imagined offenders, or harbor a grudge toward them. TABLE OF CONTENTS February 2014 Volume 17, Issue 2 Focus Editorial News and Views Reviews Brief Communications Articles Technical Report Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Reviews Neuroscience  FREE POSTER - BDNF function in health and disease This Poster summarizes the molecular functions of BDNF in the CNS and highlights its therapeutic potential for conditions such as Alzheimer's disease, Parkinson's disease, stroke and spinal cord injury. This poster is freely available thanks to support from  EVER Neuro Pharma    Focus Top Focus on pain Focus issue: February 2014 Volume 17, No 2 Editorial Reviews Editorial Top Focus on pain   p145 doi:10.1038/nn.3644 Nature Neuroscience presents a series of reviews highlighting recent progress in our understanding of the neurobiology of normal and pathological pain and itch. News and Views Top Ground zero in Alzheimer's disease   pp146 - 147 Michael A Yassa doi:10.1038/nn.3631 New findings in preclinical Alzheimer's disease patients and mouse models of the disease suggest that it is the lateral, rather than the medial, entorhinal cortex that is most susceptible to tau pathology early in Alzheimer's disease. Aberrations begin here and spread to other cortical sites. See also: Article by Khan et al. Stereotopy versus stochasticity in olfaction   pp147 - 149 Rainer W Friedrich, Anastasios Moressis and Thomas Frank doi:10.1038/nn.3630 Although projections from the insect antennal lobe to the mushroom body are probabilistic, those to the lateral horn are stereotyped, suggesting an interplay of preconfigured and plastic circuits in olfactory processing. See also: Article by Fisek & Wilson Motor variability is not noise, but grist for the learning mill   pp149 - 150 David J Herzfeld and Reza Shadmehr doi:10.1038/nn.3633 A study demonstrates that variability in how people perform a movement can predict the rate of motor learning on an individual basis. This suggests that motor 'noise' is a central component of motor learning. See also: Article by Wu et al. Stimulating memory consolidation   pp151 - 152 Serra E Favila and Brice A Kuhl doi:10.1038/nn.3638 A study in this issue of Nature Neuroscience reports that administering caffeine to humans immediately after memory encoding enhances consolidation, as reflected by improved performance in a memory test a day later. See also: Brief Communication by Borota et al. Deciphering CA2 connectivity   p152 Hannah Bayer doi:10.1038/nn0214-152 See also: Article by Kohara et al. Neuroscience JOBS of the week PhD position in Neuroscience University of Lübeck, Pharmacology Department Postdoctoral position in neuroscience UCSF Postdoctoral fellow, Neuroscience / Ischemic Stroke research Tulane University, New Orleans, Louisiana, United States Postdoc (Neuroscience) Nanyang Technological University (NTU) Assistant Professor in Neuroscience / Brain Repair / Stroke Recovery University of Ottawa More Science jobs from Neuroscience EVENT Computational Neuroscience: Vision 11th–24th July 2014 Cold Spring Harbor, USA More science events from Reviews Top Regulating excitability of peripheral afferents: emerging ion channel targets   pp153 - 163 Stephen G Waxman and Gerald W Zamponi doi:10.1038/nn.3602 Voltage-gated ion channels are key regulators of noxious signal transmission at the level of the periphery. In this Review, Zamponi and Waxman discuss recent advances in our understanding of the role of some of these channels in pain processing in primary afferent neurons, their dysfunction in congenital and acquired disease states and emerging possibilities for new analgesics. Peripheral gating of pain signals by endogenous lipid mediators   pp164 - 174 Daniele Piomelli and Oscar Sasso doi:10.1038/nn.3612 In this Review, Piomelli and Sasso survey the functions of endogenous lipid mediators in the peripheral gating of nociceptive signals. They focus on the mechanisms and pathways associated with analgesic lipids, such as endocannabinoids, lipid amides, lipoxins and resolvins, and discuss their role in the interaction between nociceptive and immune systems in the context of pain. Why we scratch an itch: the molecules, cells and circuits of itch   pp175 - 182 Diana M Bautista, Sarah R Wilson and Mark A Hoon doi:10.1038/nn.3619 Pain and itch are very distinct sensations that rely on both overlapping and orthogonal mechanisms in primary sensory afferents and in the spinal cord. In this article, Bautista, Wilson and Hoon review recent advances in our understanding of the molecular, cellular and circuit basis of acute and chronic itch in the peripheral and central nervous systems. Normal and abnormal coding of somatosensory stimuli causing pain   pp183 - 191 Steven A Prescott, Qiufu Ma and Yves De Koninck doi:10.1038/nn.3629 There is growing evidence for the existence of cross-talk between somatosensory labeled lines during the processing of noxious information, lending support to the notion that the nociceptive system operates under combinatorial encoding rules. In this Review, Prescott, Ma and De Koninck present an update on a controversy that is probably as old as the field of somatosensation itself and propose that the next step forward in our understanding of pain will necessarily involve the meticulous dissection of spinal dorsal horn microcircuitry. Pain vulnerability: a neurobiological perspective   pp192 - 200 Franziska Denk, Stephen B McMahon and Irene Tracey doi:10.1038/nn.3628 What makes certain individuals more susceptible to developing chronic pain? In this article, Denk, McMahon and Tracey review our current knowledge of the genetic, epigenetic and other environmental factors that contribute to pain vulnerability or resilience and delineate the brain networks that are involved in chronic pain states. Brief Communications Top Post-study caffeine administration enhances memory consolidation in humans   pp201 - 203 Daniel Borota, Elizabeth Murray, Gizem Keceli, Allen Chang, Joseph M Watabe et al. doi:10.1038/nn.3623 In this study, the authors examine the effects of caffeine on long-term memory. They find that a specific caffeine dose administered shortly after participants studied images improves image-recognition performance a day later. This suggests that caffeine may enhance memory consolidation separately from other cognition-enhancing effects. See also: News and Views by Favila & Kuhl An electroconvulsive therapy procedure impairs reconsolidation of episodic memories in humans   pp204 - 206 Marijn C W Kroes, Indira Tendolkar, Guido A van Wingen, Jeroen A van Waarde, Bryan A Strange et al. doi:10.1038/nn.3609 The reconsolidation hypothesis states that reactivated memory traces are vulnerable to disruption from treatments that also impair initial memory consolidation. In this study, the authors demonstrate that electroconvulsive therapy—an invasive procedure—disrupts reactivated episodic memories when tested 1 d later, but not when tested shortly after treatment. Articles Top Adult neural stem cells in distinct microdomains generate previously unknown interneuron types   pp207 - 214 Florian T Merkle, Luis C Fuentealba, Timothy A Sanders, Lorenza Magno, Nicoletta Kessaris et al. doi:10.1038/nn.3610 The authors report the generation of four previously unknown olfactory bulb interneuron subtypes by adult neural stem cells, organized into surprisingly small progenitor microdomains. These microdomains appear to be defined by unique combinations of transcription factors not previously known to be involved in adult neurogenesis, including Nkx6.2 and Zic. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain   pp215 - 222 Junjie U Guo, Yijing Su, Joo Heon Shin, Jaehoon Shin, Hongda Li et al. doi:10.1038/nn.3607 This study maps the DNA methylome profile of adult mouse dentate gyrus neurons at the single-base resolution and finds prevalent methylation of both CpG dinucleotides and non-CpG cytosines (CpH). The study also shows that CpH methylation can repress transcription. Furthermore, CpH methylation is recognized by the Rett syndrome-associated protein MeCP2, which is established during neuronal maturation and maintained by DNA methyltransferase DNMT3A. Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency   pp223 - 231 Bihua Bie, Jiang Wu, Hui Yang, Jijun J Xu, David L Brown et al. doi:10.1038/nn.3618 This study shows that the memory deficit caused by amyloid fibrils in rodents is mediated, in part, by neuroinflammation leading to histone modification via alteration of the interaction between HDAC2 and methyl-CpG-binding protein 2 (MeCP2) and resulting epigenetic modification of the neuroligin 1 promoter, causing a reduction in neuroligin 1 expression in neurons. Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease   pp232 - 239 Wei Xiong, Shao-Rui Chen, Liming He, Kejun Cheng, Yi-Lin Zhao et al. doi:10.1038/nn.3615 The authors show that a nonpsychoactive cannabinoid, DH-CBD, can rescue exaggerated acoustic startle phenotypes caused by startle disease-causing point mutations in the glycine receptor (GlyR) α1 subunit. Homomeric and presynaptic GlyRs showed significant impairment as a result of these mutations, which was selectively rescued by DH-CBD. Tbr1 haploinsufficiency impairs amygdalar axonal projections and results in cognitive abnormality   pp240 - 247 Tzyy-Nan Huang, Hsiu-Chun Chuang, Wen-Hsi Chou, Chiung-Ya Chen, Hsiao-Fang Wang et al. doi:10.1038/nn.3626 The authors show that mice lacking one copy of gene encoding the transcription factor T-box brain 1 (TBR1) show deficient axonal projections from amygdala neurons, as well as social and cognitive behavioral deficits. Tbr1 haploinsufficiency alters expression of multiple TBR1 target genes, and restoring their expression restores axon outgrowth defects in vivo. Medial prefrontal D1 dopamine neurons control food intake   pp248 - 253 Benjamin B Land, Nandakumar S Narayanan, Rong-Jian Liu, Carol A Gianessi, Catherine E Brayton et al. doi:10.1038/nn.3625 The authors show that dopamine receptor 1 (D1)-expressing neurons in the medial prefrontal cortex (mPFC) of mice show increased activity in response to food intake. Using optogenetic stimulation and inhibition, they show that mPFC D1 neuron projections to the medial basolateral amygdala can increase or decrease food intake, respectively. Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward   pp254 - 261 Yijun Cui, Sean B Ostlund, Alex S James, Chang Sin Park, Weihong Ge et al. doi:10.1038/nn.3622 μ-opioid receptor (MOR) was previously shown to be necessary for opiate reward, analgesia and dependence. To better understand the specific anatomical and cell type loci of MOR action in opiate reward and reinforcement learning, the authors use cell-specific rescue expression of MOR in subtypes of neurons in the mouse brain that lack MOR globally and show that MOR in the striatal direct-pathway medium spiny neurons is sufficient to rescue the reward action of opioids without affecting opioid analgesia or withdrawal in MOR knockout mice. Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina   pp262 - 268 Tzu-Ming Wang, Lars C Holzhausen and Richard H Kramer doi:10.1038/nn.3627 The mechanism behind lateral inhibition that establishes the receptive fields of retinal neurons has remained elusive. Here the authors show that synaptic proton concentration mediates horizontal cell negative feedback in the retina and that this transmission depends on activity of a proton pump and proton-permeant ion channel. Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits   pp269 - 279 Keigo Kohara, Michele Pignatelli, Alexander J Rivest, Hae-Yoon Jung, Takashi Kitamura et al. doi:10.1038/nn.3614 The authors use cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings to provide new insights into hippocampal anatomy and function. They find that dentate granule cells of the hippocampus, which were believed to not project to CA2, do indeed send functional monosynaptic inputs to CA2 pyramidal cells. CA2 innervates CA1, but, unlike CA3, projects preferentially to the deep rather than superficial sublayer of CA1. Moreover, the authors find that layer 3 of the entorhinal cortex does not project to CA2. See also: News and Views by Bayer Stereotyped connectivity and computations in higher-order olfactory neurons   pp280 - 288 Mehmet Fisek and Rachel I Wilson doi:10.1038/nn.3613 The authors describe how glomerular signals are combined to generate odor representations in the Drosophila lateral horn region. They observe stereotypy and over-representation of certain glomerular combinations, a wiring pattern that contrasts with reports from the mushroom body but is consistent with roles of these regions in innate versus learned behaviors. See also: News and Views by Friedrich et al. Ultra-rapid axon-axon ephaptic inhibition of cerebellar Purkinje cells by the pinceau   pp289 - 295 Antonin Blot and Boris Barbour doi:10.1038/nn.3624 Inhibition sculpts neural activity through various cell types and circuits, but, unlike excitation, it is not self-propagating and must be locally recruited with a temporal delay. Here the authors show a fast, feedforward inhibitory mechanism that bypasses synaptic delay through ephaptic coupling of an interneuron to the axon initial segment of a projection cell. Flies and humans share a motion estimation strategy that exploits natural scene statistics   pp296 - 303 Damon A Clark, James E Fitzgerald, Justin M Ales, Daryl M Gohl, Marion A Silies et al. doi:10.1038/nn.3600 Current models of how animals estimate motion involve correlations between pairs of points in space and time. Here the authors show that both fly and human visual systems can encode the direction and contrast polarity of moving edges using three-point correlations, and that this enhances motion estimation accuracy. Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease   pp304 - 311 Usman A Khan, Li Liu, Frank A Provenzano, Diego E Berman, Caterina P Profaci et al. doi:10.1038/nn.3606 In the brains of Alzheimer's disease patients, the entorhinal cortex is known to show signs of early pathology. In this study, Khan et al. performed cerebral blood volume imaging of patients with preclinical Alzheimer's disease and mouse models of disease. Their results pinpoint the subregion in the entorhinal cortex most sensitive to the disease, and show how amyloid and tau interact in driving dysfunction and how dysfunction spreads to distal cortical regions. See also: News and Views by Yassa Temporal structure of motor variability is dynamically regulated and predicts motor learning ability   pp312 - 321 Howard G Wu, Yohsuke R Miyamoto, Luis Nicolas Gonzalez Castro, Bence P Ölveczky and Maurice A Smith doi:10.1038/nn.3616 Here the authors report that higher levels of task-relevant motor variability predict faster learning both across individuals and across tasks in two different paradigms and that training can reshape the temporal structure of motor variability, aligning it with the trained task to improve learning. These results support the importance of action exploration, a key idea from reinforcement learning theory. See also: News and Views by Herzfeld & Shadmehr Technical Report Top Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans   pp322 - 329 Wynn Legon, Tomokazu F Sato, Alexander Opitz, Jerel Mueller, Aaron Barbour et al. doi:10.1038/nn.3620 Existing noninvasive neuromodulation methods have poor spatial resolution and may affect neural activity in both the targeted cortical region and unintended surrounding networks. The authors demonstrate that transcranial focused ultrasound, a noninvasive technique with better spatial specificity, can alter neural activity within spatially confined regions of primary somatosensory cortex and enhance somatosensory discrimination. Top Advertisement Nature Collections  LIGHT-SHEET MICROSCOPY  The use of a planar sheet of light for illumination in light-sheet fluorescence microscopy allows researchers to image sample volumes faster than is possible with other current methods, while limiting light dosage. 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