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Volume 16 Issue 11, November 2013

Using a new mouse model, the authors show that deletion of TGF-β-activated kinase 1 (TAK1) specifically in microglial cells reduces pathology in a mouse model of multiple sclerosis via the inhibition of NF-κB, ERK and JNK signaling pathways. On the cover is an IMARIS-based three-dimensional reconstruction of a microglial cell.p 1618


  • Dysregulation of protein translation and RNA processing mechanisms in the brain can result in subtle, but widespread, neurological disorders. A collection of Review and Perspective articles in this issue of Nature Neuroscience highlights some of the more unconventional mechanisms of post-transcriptional modifications in the CNS.



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News & Views

  • We know that humans are capable of learning during sleep. Research now shows that they are also capable of unlearning during sleep, and in a way that alters the neural representation of a feared stimulus: re-exposure to an odor during slow-wave sleep promotes extinction of an aversive visual association learned in that odor context.

    • John T Wixted
    News & Views
  • Two studies emphasize similarities in the developmental origin of cortical interneurons across mammals. They suggest that most interneurons in humans and macaques have a subcortical origin.

    • Zoltán Molnár
    • Simon J B Butt
    News & Views
  • A study now identifies an unexpected function of the D2 dopamine receptor in synapse maturation during a critical period in mice. The findings may have implications for the onset of schizophrenia in humans.

    • Dong-Min Yin
    • Wen-Cheng Xiong
    • Lin Mei
    News & Views
  • Each olfactory sensory neuron in mice is defined by which of the 1,000 odorant receptor genes that it expresses. Using optogenetics, a study finds that mice can perceive stimulation of only a single class of olfactory sensory neuron.

    • Nathan E Schoppa
    News & Views
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Review Article

  • Brain enriched RNA editing of Adenosine-to-Inosine (A-to-I) increases the amount of information encoded in the genome and diversifies the transcriptome. Here the authors discuss how recent technological and analytical developments may facilitate the discovery of RNA editing sites and the understanding of their functions and regulation.

    • Jin Billy Li
    • George M Church
    Review Article
  • This review article by Peter McKinnon discusses the latest progress in understanding the complexity of DNA damage and related repair pathways in the nervous system. The piece highlights DNA damage/repair in both normal course of brain development and in aging, and discusses possible dysfunction of this mechanism in disease as uniquely faced by postmitotic neurons in the brain.

    • Peter J McKinnon
    Review Article
  • In this review, the authors discuss the function of fragile X mental retardation protein (FMRP) in regulating the synthesis of plasticity-related target proteins. The authors review the known mRNA targets of FMRP and discuss the potential therapeutic implications of this research.

    • Jennifer C Darnell
    • Eric Klann
    Review Article
  • Mechanistic target of rapamycin (mTOR) integrates a variety of inputs and regulates diverse cellular functions. In this review, the authors discuss recent studies implicating mTOR signaling in neurodevelopmental and psychiatric diseases, and the mechanisms that may underlie these effects.

    • Mauro Costa-Mattioli
    • Lisa M Monteggia
    Review Article
  • Here the authors review emerging evidence from circadian systems, indicating an important role for post-transcriptional regulation, from splicing, polyadenylation and mRNA stability to translation and noncoding functions exemplified by microRNAs. They hypothesize that post-transcriptional control confers to circadian clocks enhanced robustness as well as the ability to adapt to different environments.

    • Chunghun Lim
    • Ravi Allada
    Review Article
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Brief Communication

  • It has been suggested that posterior insular regions code lower-level sensory information and anterior regions code higher-level stimulus significance relative to the body's homeostatic needs. However, here the authors report that the caudal, but not rostral, insula response to food images was directly related to the body's homeostatic state.

    • W Kyle Simmons
    • Kristina M Rapuano
    • Alex Martin
    Brief Communication
  • Sleep has been shown to strengthen various types of memory, including emotional memory. Here the authors show that in subjects who have learned to associate an odor with an electric shock, re-exposure to the odor during slow-wave sleep promotes extinction of the memory for the odor-shock association.

    • Katherina K Hauner
    • James D Howard
    • Jay A Gottfried
    Brief Communication
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  • The authors show that shortening of the basal process in neural progenitor cells by depletion of TAG-1 results in overcrowding in the periventricular space and, eventually, delamination and aberrant migration. These results suggest that one of the functions of interkinetic nuclear migration is to prevent progenitor congestion and mechanical stress.

    • Mayumi Okamoto
    • Takashi Namba
    • Takaki Miyata
  • GABAergic cortical interneurons have important roles in the computations of neural circuits, but their developmental origin in primates is controversial. Here the authors characterize neural stem cell and progenitor cell organization in the developing human ganglionic eminences and reveal that, just as in rodents, they give rise to a majority of cortical GABAergic neurons.

    • David V Hansen
    • Jan H Lui
    • Arnold R Kriegstein
  • In primates, the developmental origin of neocortical interneurons is controversial. Here the authors map out expression patterns of key transcription factors in the developing human and monkey brain and reveal that, just as in rodents, the majority of cortical GABAergic neurons originate from the ganglionic eminences.

    • Tong Ma
    • Congmin Wang
    • Zhengang Yang
  • There is a diverse set of cortical interneurons that uniquely participate in the computations of large cell assemblies. Here the authors show that the same type of interneuron within the hippocampus, those projecting to the oriens-lacunosum moleculare, can have distinct developmental origins and different circuit functions.

    • Ramesh Chittajallu
    • Michael T Craig
    • Chris J McBain
  • In this study, the authors generate a new mouse model that allows selective genetic targeting of microglial cells. Using this model, they show that elimination of TGF-β-activated kinase 1 (TAK1) specifically in microglial cells reduces pathology in a mouse model of multiple sclerosis by inhibiting NF-κB, ERK and JNK signaling pathways.

    • Tobias Goldmann
    • Peter Wieghofer
    • Marco Prinz
  • The authors show that type 2 dopamine receptors (D2Rs) negatively regulate spine morphogenesis in the hippocampi of adolescent mice. Spine deficiency resulting from D2R overactivation was associated with dysconnectivity in the entorhinal-hippocampal circuit and working memory deficits. These phenotypes could be rescued by D2R antagonists given during adolescence.

    • Jie-Min Jia
    • Jun Zhao
    • Zheng Li
  • The authors find that optogenetic stimulation of melanin-concentrating hormone (MCH)-expressing neurons in the lateral hypothalamus selectively extends the duration of paradoxical sleep episodes in mice. Activation of MCH fibers in the tuberomammillary nucleus leads to the release of GABA and a similar increase in paradoxical sleep stability.

    • Sonia Jego
    • Stephen D Glasgow
    • Antoine R Adamantidis
  • In rats self-administering cocaine, drug seeking behavior induced by a cocaine-paired cue increases progressively during cocaine withdrawal. The authors detected silent synapses in basolateral amygdala–to–nucleus accumbens projections during early withdrawal, but these synapses progressively disappeared during protracted withdrawal. Optogenetic 're-silencing' of these synapses decreased cue-induced cocaine seeking following withdrawal.

    • Brian R Lee
    • Yao-Ying Ma
    • Yan Dong
  • α7-nicotinic acetylcholine receptors (α7nAChRs) modulate the effects of the main psychoactive ingredient of marijuana, Δ9-tetrahydrocannabinol (THC), in the brain. Here the authors show that pharmacologically enhancing kynurenic acid, an endogenous modulator of α7nAChRs, attenuated the rewarding properties of THC and prevented drug relapse in monkeys and rats.

    • Zuzana Justinova
    • Paola Mascia
    • Steven R Goldberg
  • The authors find that long-range axons from primary motor cortex (vM1) preferentially recruit vasointestinal peptide (VIP)-expressing interneurons in somatosensory cortex (S1). VIP neurons in turn inhibit somatostatin-expressing interneurons that target the distal dendrites of pyramidal cells in S1. This dis-inhibitory circuit is active during voluntary movement, suggesting that it participates in the modulation of primary cortical sensory processing by motor cortex.

    • Soohyun Lee
    • Illya Kruglikov
    • Bernardo Rudy
  • Here the authors demonstrate a causal role for the barrel cortex in the detection of single whisker stimuli. Whisker deflection evoked an early (<50 ms) reliable sensory response that was encoded through cell-specific reversal potentials. A secondary late (50–400 ms) depolarization was enhanced in hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation.

    • Shankar Sachidhanandam
    • Varun Sreenivasan
    • Carl C H Petersen
  • Using optogenetics and other methods in the zebrafish olfactory bulb, the authors explore the role of interneurons that are densely connected to mitral cells (MCs) by both electrical and chemical synapses. These interneurons maintain the mean and distribution of MC population activity within narrow limits as stimulus intensity changes.

    • Peixin Zhu
    • Thomas Frank
    • Rainer W Friedrich
  • The authors use optogenetics to selectively activate single glomeruli in behaving mice. They find that mice can perceive the stimulation of a single glomerulus, even on an intense odor background. Different input intensities and the timing of input relative to sniffing can also be discriminated. This suggests that each glomerulus can transmit odor information using identity, intensity and temporal coding cues.

    • Matthew Smear
    • Admir Resulaj
    • Dmitry Rinberg
  • The origin and functional importance of noise in mammalian cones is poorly understood. Here, the authors find that channel noise and fluctuations in cGMP dominate cone noise, that adaptation in cones affects signal and noise differently, and that cones generate less noise than previously thought. These results help reconcile cone noise and behavioral sensitivity.

    • Juan M Angueyra
    • Fred Rieke
  • In this study, the authors recorded from the cerebellum while monkeys experienced an illusory perception of self-motion, and found that the neurons encoded the erroneous linear acceleration. Their findings provide evidence that the cerebellum might be involved in the implementation of internal models, as previously hypothesized by theorists.

    • Jean Laurens
    • Hui Meng
    • Dora E Angelaki
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