Current issue
November 2010, Volume 13 No 11 pp1299-1440
Life experiences affect behavior, in part by altering DNA via epigenetic modifications. These epigenetic changes include histone or chromatin modifications and can silence genes or make them easier to read. Recently, neuroscientists have also begun to explore epigenetic mechanisms to help explain the influence of experiences on not only long-term behavior, but also on neural development and function. Nature Neuroscience presents a special focus on this growing field of neural epigenetics consisting of commentaries, perspectives and reviews. These articles highlight the latest advances in our understanding of these epigenetic mechanisms, their regulation and their role in the nervous system.
Editorial
Focus on Epigenetics
Focus on epigenetics - p1299
doi:10.1038/nn1110-1299
We present a special focus on epigenetics in the nervous system, highlighting recent advances in our understanding of epigenetic mechanisms and their regulation in neurons, as well as their role in nervous system function.
Book Review
Taking animal rights personally - p1301
An Odyssey with Animals: A Veterinarian's Reflections on the Animal Rights & Welfare Debate by Adrian R Morrison
doi:10.1038/nn1110-1301
News and Views
Bringing SOD1 into the fold - pp1303 - 1304
Sami Barmada & Steven Finkbeiner
doi:10.1038/nn1110-1303
Could similar changes in superoxide dismutase 1 (SOD1) underlie both familial and sporadic amyotrophic lateral sclerosis (ALS)? A new study finds that wild-type SOD1 from sporadic ALS tissues shows conformational changes similar to those seen in familial ALS and may be pathogenic as a result of the same mechanism.
See also: Article by Bosco et al.
Categorizing speech - pp1304 - 1306
Sophie K Scott & Samuel Evans
doi:10.1038/nn1110-1304
Using direct electrode recordings in patients undergoing preoperative surgery, a new study demonstrates that neural responses in the secondary auditory cortex mirror perception, showing categorical responses to continuous stimuli.
See also: Article by Chang et al.
“Yes! We're all individuals!”: redundancy in neuronal circuits - pp1306 - 1307
Timothy E Holy
doi:10.1038/nn1110-1306
In the mouse olfactory bulb, cells with common input respond to odors with similar firing rates but with different timing. This suggests that such 'sister' cells make independent and unique connections with local interneurons.
Full Text - “Yes! We're all individuals!”: redundancy in neuronal circuits | PDF (260 KB) - “Yes! We're all individuals!”: redundancy in neuronal circuits
See also: Article by Dhawale et al.
Making glutamatergic neurons from GABAergic progenitors - pp1308 - 1309
Magdalena Götz
doi:10.1038/nn1110-1308
The mature phenotype of CNS neurons is thought to be set at an early progenitor stage. A study now shows that expression of Fezf2 alone can turn striatal GABAergic precursors into glutamatergic corticofugal neurons.
Full Text - Making glutamatergic neurons from GABAergic progenitors | PDF (183 KB) - Making glutamatergic neurons from GABAergic progenitors
See also: Brief Communication by Rouaux & Arlotta
I see where you're hearing: how cross-modal plasticity may exploit homologous brain structures - pp1309 - 1311
Daphne Bavelier & Elizabeth A Hirshorn
doi:10.1038/nn1110-1309
Sensory deprivation such as deafness or blindness leads to specific functional and neural reorganization. A new study gives insight into why and how certain abilities change, while others remain unaltered after the loss of a sense.
Full Text - I see where you're hearing: how cross-modal plasticity may exploit homologous brain structures | PDF (456 KB) - I see where you're hearing: how cross-modal plasticity may exploit homologous brain structures
See also: Article by Lomber et al.
The importance of degradation - p1311
Annette Markus
doi:10.1038/nn1110-1311
See also: Article by Hoeck et al.
Commentary
Focus on Epigenetics
Epigenetic regulation of the neural transcriptome: the meaning of the marks - pp1313 - 1318
Michael J Meaney & Anne C Ferguson-Smith
doi:10.1038/nn1110-1313
This commentary provides a nuanced discussion on the conceptual framework to study epigenetic mechanisms that regulate brain function and plasticity. By drawing from examples in genomic imprinting, the authors highlight the challenges facing epigenetics research in the context of neuroscience.
Perspectives
Focus on Epigenetics
DNA methylation and memory formation - pp1319 - 1323
Jeremy J Day & J David Sweatt
doi:10.1038/nn.2666
Disruption of DNA methylation in the brain can impair learning and memory in rodents. In this Perspective, Day and Sweatt provide an overview of evidence that implicates this epigenetic mechanism in memory processes and discuss how past controversies can be explained in light of recent findings.
Focus on Epigenetics
Plasticity and specificity of the circadian epigenome - pp1324 - 1329
Selma Masri & Paolo Sassone-Corsi
doi:10.1038/nn.2668
This perspective discusses the role of epigenetic mechanisms in regulating circadian rhythms, and emphasizes that the role of peripheral machinery is key for a fuller understanding of this regulation.
Reviews
Focus on Epigenetics
Dynamic epigenetic regulation in neurons: enzymes, stimuli and signaling pathways - pp1330 - 1337
Antonella Riccio
doi:10.1038/nn.2671
This Review discusses the current knowledge regarding regulation of epigenetic modifications and mechanisms in the nervous system in response to dynamic signals such as developmental stage, growth factors and synaptic activity.
Focus on Epigenetics
Epigenetic choreographers of neurogenesis in the adult mammalian brain - pp1338 - 1344
Dengke K Ma, Maria Carolina Marchetto, Junjie U Guo, Guo-li Ming, Fred H Gage & Hongjun Song
doi:10.1038/nn.2672
This review examines evidence supporting diverse roles for epigenetic mechanisms in regulating specific aspects of adult neurogenesis and their implications.
Brief Communications
Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo - pp1345 - 1347
Caroline Rouaux & Paola Arlotta
doi:10.1038/nn.2658
Rouaux and Arlotta show that expression of a single transcription factor, Fezf2, suffices to turn ventral forebrain progenitors committed to a striatal GABAergic fate into glutamatergic corticofugal projection neurons—which nevertheless migrate to the striatum.
Abstract - Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo | Full Text - Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo | PDF (1,240 KB) - Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo | Supplementary information
See also: News and Views by Götz
N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release - pp1348 - 1350
Alexander M Weber, Fiona K Wong, Adele R Tufford, Lyanne C Schlichter, Victor Matveev & Elise F Stanley
doi:10.1038/nn.2657
The established conductance hierarchy of voltage-gated calcium channels, where conductance of CaV1 is greater than CaV2, which is in turn greater than CaV3, was determined using nonphysiological divalent ion concentrations. Weber et al. find that CaV2.2 conductance is greater than that of CaV1 and CaV3 and investigate implications for Ca2+ nanodomain signaling.
Abstract - N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release | Full Text - N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release | PDF (431 KB) - N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release | Supplementary information
Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice - pp1351 - 1353
Evan Elliott, Gili Ezra-Nevo, Limor Regev, Adi Neufeld-Cohen & Alon Chen
doi:10.1038/nn.2642
Corticotrophin releasing factor (CRF) and its receptors are involved in the neuroendocrine and behavioral responses to stress. Here, Elliot and colleagues describe alterations in DNA methylation of the Crf gene that regulate its expression and show that these alterations correlate with resilience to social stress.
Abstract - Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice | Full Text - Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice | PDF (383 KB) - Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice | Supplementary information
The habenula is crucial for experience-dependent modification of fear responses in zebrafish - pp1354 - 1356
Masakazu Agetsuma, Hidenori Aizawa, Tazu Aoki, Ryoko Nakayama, Mikako Takahoko, Midori Goto, Takayuki Sassa, Ryunosuke Amo, Toshiyuki Shiraki, Koichi Kawakami, Toshihiko Hosoya, Shin-ichi Higashijima & Hitoshi Okamoto
doi:10.1038/nn.2654
Agetsuma and colleagues find that the pathway between the lateral subnucleus of the dorsal habenula (dHbL) and the interpeduncular nucleus is involved in mediating experience-dependent fear responses in zebrafish. Genetic inactivation of the dHbL biased fish towards freezing, rather than the typical flight behavior, in response to a conditioned fear stimulus.
Abstract - The habenula is crucial for experience-dependent modification of fear responses in zebrafish | Full Text - The habenula is crucial for experience-dependent modification of fear responses in zebrafish | PDF (587 KB) - The habenula is crucial for experience-dependent modification of fear responses in zebrafish | Supplementary information
Articles
APC/CFzr/Cdh1-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS - pp1357 - 1364
Marion Silies & Christian Klämbt
doi:10.1038/nn.2656
For young glia to migrate along motor axons in the developing fly, their adhesion to the axon must be broken. Silies and Klämbt show that this is accomplished by removal of Fas2 from the axonal membrane, involving a ubiquitin ligase complex that has previously been implicated only in cell cycle regulation.
Abstract - APC/CFzr/Cdh1-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS | Full Text - APC/CFzr/Cdh1-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS | PDF (2,543 KB) - APC/CFzr/Cdh1-dependent regulation of cell adhesion controls glial migration in the Drosophila PNS | Supplementary information
Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun - pp1365 - 1372
Joerg D Hoeck, Anett Jandke, Sophia M Blake, Emma Nye, Bradley Spencer-Dene, Sebastian Brandner & Axel Behrens
doi:10.1038/nn.2644
This study demonstrates that Fbw7, a component of ubiquitin ligase complex, regulates neural progenitor cell viability and differentiation by controlling Notch and JNK/c-Jun signaling.
Abstract - Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun | Full Text - Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun | PDF (3,220 KB) - Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun | Supplementary information
See also: News and Views by Markus
The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching - pp1373 - 1379
Freddy Jeanneteau, Katrin Deinhardt, Goichi Miyoshi, Anton M Bennett & Moses V Chao
doi:10.1038/nn.2655
How extracellular signals, such as BDNF, regulate axonal branching is unclear. Here, Jeanneteau et al. find that MAP kinase phosphatase 1 expression is induced by BDNF signaling to deactivate JNK. This negatively regulates phosphorylation of JNK substrates that impinge on microtubule destabilization. Neurons from mkp-1 null mice were unable to produce BDNF-induced axon branches.
Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway - pp1380 - 1387
Coralie Fassier, James A Hutt, Steffen Scholpp, Andrew Lumsden, Bruno Giros, Fatiha Nothias, Sylvie Schneider-Maunoury, Corinne Houart & Jamilé Hazan
doi:10.1038/nn.2662
Hereditary spastic paraplegia (HSP) is manifested as motor dysfunction stemming from axonal degeneration. Of the known 19 spastic paraplegia genes (SPGs), SPG3a encodes a multimeric integral membrane protein Atlastin. Here, the authors use zebrafish system to demonstrate the interplay between Atlastin and bone morphogenic protein signaling in motor axon development and stability.
Abstract - Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway | Full Text - Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway | PDF (2,208 KB) - Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway | Supplementary information
A crosstalk between β1 and β3 integrins controls glycine receptor and gephyrin trafficking at synapses - pp1388 - 1395
Cécile Charrier, Patricia Machado, Ry Y Tweedie-Cullen, Dorothea Rutishauser, Isabelle M Mansuy & Antoine Triller
doi:10.1038/nn.2645
Integrins connect cells to the extracellular matrix and mediate neuron-neuron or neuron-glia interactions during synapse maturation and synaptic plasticity. Here, Charrier et al. find that integrins β1 and β3 exert opposing actions via CaMKII to regulate glycine receptor lateral diffusion and gephyrin trafficking at the inhibitory synapses in spinal cord neurons.
Abstract - A crosstalk between [beta]1 and [beta]3 integrins controls glycine receptor and gephyrin trafficking at synapses | Full Text - A crosstalk between β1 and β3 integrins controls glycine receptor and gephyrin trafficking at synapses | PDF (1,258 KB) - A crosstalk between β1 and β3 integrins controls glycine receptor and gephyrin trafficking at synapses | Supplementary information
Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS - pp1396 - 1403
Daryl A Bosco, Gerardo Morfini, N Murat Karabacak, Yuyu Song, Francois Gros-Louis, Piera Pasinelli, Holly Goolsby, Benjamin A Fontaine, Nathan Lemay, Diane McKenna-Yasek, Matthew P Frosch, Jeffrey N Agar, Jean-Pierre Julien, Scott T Brady & Robert H Brown Jr
doi:10.1038/nn.2660
Could similar changes in SOD1 underlie both familial and sporadic ALS? Here, Bosco et al. find that wild-type SOD1 from sporadic ALS tissues shows conformational changes similar to those seen in familial ALS and that aberrant wild-type SOD1 can be pathogenic, potentially as a result of the same SOD1-dependent mechanism seen in familial ALS.
Abstract - Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS | Full Text - Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS | PDF (1,376 KB) - Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS | Supplementary information
See also: News and Views by Barmada & Finkbeiner
Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse - pp1404 - 1412
Ashesh K Dhawale, Akari Hagiwara, Upinder S Bhalla, Venkatesh N Murthy & Dinu F Albeanu
doi:10.1038/nn.2673
Using optogenetic techniques, Dhawale et al. find that, although sister mitral cells (which receive input from the same olfactory glomerulus) have highly correlated average spike rate responses, their spike timing with respect to respiration differs. This suggests that sister cells carry both correlated and independent information.
Abstract - Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse | Full Text - Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse | PDF (1,695 KB) - Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse | Supplementary information
See also: News and Views by Holy
The functional asymmetry of auditory cortex is reflected in the organization of local cortical circuits - pp1413 - 1420
Hysell V Oviedo, Ingrid Bureau, Karel Svoboda & Anthony M Zador
doi:10.1038/nn.2659
Primary auditory cortex is organized tonotopically along one axis. Using laser scanning photostimulation in acute slices, the authors find that local connections along the tonotopic axis differ from those along the orthogonal, isofrequency axis.
Abstract - The functional asymmetry of auditory cortex is reflected in the organization of local cortical circuits | Full Text - The functional asymmetry of auditory cortex is reflected in the organization of local cortical circuits | PDF (2,543 KB) - The functional asymmetry of auditory cortex is reflected in the organization of local cortical circuits | Supplementary information
Cross-modal plasticity in specific auditory cortices underlies visual compensations in the deaf - pp1421 - 1427
Stephen G Lomber, M Alex Meredith & Andrej Kral
doi:10.1038/nn.2653
Lomber and colleagues find that enhanced visual localization and motion detection in deaf cats is subserved by cross-modal reorganization of cortex that is typically dedicated to auditory function. Furthermore, the authors localize the individual visual functions to discrete portions of reorganized auditory cortex.
Abstract - Cross-modal plasticity in specific auditory cortices underlies visual compensations in the deaf | Full Text - Cross-modal plasticity in specific auditory cortices underlies visual compensations in the deaf | PDF (1,097 KB) - Cross-modal plasticity in specific auditory cortices underlies visual compensations in the deaf | Supplementary information
See also: News and Views by Bavelier & Hirshorn
Categorical speech representation in human superior temporal gyrus - pp1428 - 1432
Edward F Chang, Jochem W Rieger, Keith Johnson, Mitchel S Berger, Nicholas M Barbaro & Robert T Knight
doi:10.1038/nn.2641
A continuum of acoustically varying speech sounds is not perceived as a continuum, but as distinct phonetic categories. Chang et al. recorded directly from human posterior superior temporal gyrus and found that this area has a similarly discontinuous coding of objectively continuous sound, matching perception and indicating higher-level processing.
Abstract - Categorical speech representation in human superior temporal gyrus | Full Text - Categorical speech representation in human superior temporal gyrus | PDF (691 KB) - Categorical speech representation in human superior temporal gyrus | Supplementary information
See also: News and Views by Scott & Evans
Technical Report
Functional imaging of hippocampal place cells at cellular resolution during virtual navigation - pp1433 - 1440
Daniel A Dombeck, Christopher D Harvey, Lin Tian, Loren L Looger & David W Tank
doi:10.1038/nn.2648
Dombeck and colleagues describe a method for two-photon calcium imaging using a genetically encoded indicator in the hippocampus of awake, behaving mice. This powerful approach permits the recording of multiple hippocampal place cells' activity with subcellular resolution as the mice run on a track in a virtual reality environment.
Abstract - Functional imaging of hippocampal place cells at cellular resolution during virtual navigation | Full Text - Functional imaging of hippocampal place cells at cellular resolution during virtual navigation | PDF (1,597 KB) - Functional imaging of hippocampal place cells at cellular resolution during virtual navigation |
