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Volume 17 Issue 1, January 2014

In this issue, Dias and Ressler provide evidence supporting epigenetic inheritance of a learned behavior. Learning about a specific olfactory stimulus changed brain structure and the behavior of future generations, with transmission across generations via epigenetic changes in the gametes. On the cover is Jean-Baptiste Lamarck, known for his theory of the inheritance of acquired characteristics. Credit: INTERFOTO / Alamy.289


  • The BRAIN initiative is set to award its first grants this year. It is imperative that this initiative be funded appropriately for neuroscientists to fully reap its benefits.



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News & Views

  • A study shows that when mice are taught to fear an odor, both their offspring and the next generation are born fearing it. The gene for an olfactory receptor activated by the odor is specifically demethylated in the germ line and the olfactory circuits for detecting the odor are enhanced.

    • Moshe Szyf
    News & Views
  • Long-term exposure to females reduces aggression of male fruit flies. The mechanism involves contact-dependent pheromone sensing and the activation of a small group of GABAergic inhibitory neurons unique to the male brain.

    • Liming Wang
    News & Views
  • While effectively doubling the number of known odorant-to-receptor pairings in human olfaction, researchers explain a portion of perceptual variability that stems from genetic variability.

    • Idan Frumin
    • Noam Sobel
    • Yoav Gilad
    News & Views
  • A study finds that immune factors transmitted through breast milk regulate the cognitive function of offspring. Changes in milk composition alter hippocampal development and have effects on memory that last into adulthood.

    • Sarah L Parylak
    • Wei Deng
    • Fred H Gage
    News & Views
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Review Article

  • From FM dyes, cypHers, pHluorin and Q-dots to electron tomography and super-resolution microscopy, Kavalali and Jorgensen present a critical survey of the optical paraphernalia currently available to investigate presynaptic function, highlighting the specific strengths and limitations inherent to these various approaches.

    • Ege T Kavalali
    • Erik M Jorgensen
    Review Article
  • In this review, the authors examine how the identification and analysis of genes associated with ALS have begun to provide insight into the onset and pathology of this motor disease. In addition, they discuss some emerging themes that are poised to inform future efforts to identify further gene targets.

    • Alan E Renton
    • Adriano Chiò
    • Bryan J Traynor
    Review Article
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Brief Communication

  • Transplanted neurons often fail to migrate sufficiently into host brain tissue. In this study, the authors show that this migration deficiency may not be the result of a nonpermissive host environment but instead is due to a chemoattractive effect of grafted neural precursors on their own neuronal progeny.

    • Julia Ladewig
    • Philipp Koch
    • Oliver Brüstle
    Brief Communication
  • Chronic social-defeat stress increases phasic firing of ventral tegmental area (VTA) neurons and increases the amount of BDNF in the nucleus accumbens (NAc). The authors show that increased activity of NAc-projecting VTA neurons is sufficient to increase the amount of BDNF in the NAc, an effect that depends on CRF signaling in the NAc.

    • Jessica J Walsh
    • Allyson K Friedman
    • Ming-Hu Han
    Brief Communication
  • Here the authors used optogenetic stimulation to trigger antidromic spikes in a local region of primary visual cortex. This local activity caused two effects at distal locations: summation and division. The balance between the two depended on visual contrast, and a normalization model captured these effects.

    • Tatsuo K Sato
    • Michael Häusser
    • Matteo Carandini
    Brief Communication
  • The authors find that pharmacological inactivation of the lateral habenula leaves rats indifferent when choosing between rewards associated with different costs and benefits. These data show that the lateral habenula not only signals aversion but also functions as a preference center to promote subjective decision biases during goal-directed behavior.

    • Colin M Stopper
    • Stan B Floresco
    Brief Communication
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  • In this study, the authors report that target-derived NGF signaling induces the expression of Coronin-1, which consequently gets recruited to the NGF-TrkA–carrying signaling endosome, where it regulates endosomal fusion with lysosomes, trafficking and recycling. In addition, Coronin-1 appears to be necessary for NGF-dependent signaling events such as CREB phosphorylation, Ca2+ release and activation of calcineurin.

    • Dong Suo
    • Juyeon Park
    • Christopher D Deppmann
  • Growth of malignant glioma involves a rare population of stem-like cells in the brain called brain tumor-initiating cells (BTICs). This study shows that immune cells in the brain can attenuate tumorigenic capacity of cancer patient-derived BTICs. The authors also identify a drug amphotericin B as an activator of microglia and macrophages that can enhance the microglial activation and mitigate BTIC proliferation in culture. This drug also improved the lifespan of a mouse model of malignant glioma in vivo.

    • Susobhan Sarkar
    • Axinia Döring
    • V Wee Yong
  • This study shows that neuroligin-1, a trans-synaptic cell adhesion molecule for excitatory synapses, is directly phosphorylated by Ca2+/CaM kinase II in a neuronal activity–dependent manner in vitro and in vivo. The authors also show that this post-translational modification of neuroligin-1 regulates excitatory synaptic potentiation.

    • Michael A Bemben
    • Seth L Shipman
    • Katherine W Roche
  • Neurons in the lateral amygdala (LA) with high expression of the transcription factor CREB at the time of fear learning are known to be preferentially recruited to the activated neuronal network for memory recall. The current study shows that artificial activation of high CREB expressing–neurons in the LA using the vanilloid receptor TRPV1 and capsaicin system is sufficient to induce memory recall and promote memory consolidation without external cue and reminders.

    • Jieun Kim
    • Jeong-Tae Kwon
    • Jin-Hee Han
  • Accumulation of calcium-permeable AMPA receptors at nucleus accumbens synapses underlies the intensified cue-induced cocaine craving observed after prolonged withdrawal, a phenomenon that may contribute to relapse. Here, Loweth and colleagues find that administration of mGluR1 positive allosteric modulators can normalize accumbens AMPAR transmission and curb cocaine craving in rats.

    • Jessica A Loweth
    • Andrew F Scheyer
    • Marina E Wolf
  • This study shows that aggressive behavior by male Drosophila melanogaster to another male is attenuated when the aggressor male fly had prior exposure to females. The study also shows that this prior experience-dependent modulation of aggression behavior is mediated by a sexually dimorphic neural circuit and pheromone-based contact chemosensation mechanism.

    • Quan Yuan
    • Yuanquan Song
    • Yuh Nung Jan
  • This study demonstrates an epigenetic inheritance of a learned behavior that is transmitted across generations via the gametes whereby learning about a specific olfactory stimulus changes brain structure and the behavior of future generations. Specifically, Dias and Ressler show that behavioral response to olfactory fear conditioning in male parents is transmitted to their offspring via DNA methylation changes in the corresponding odorant receptor gene in the sperm, which is accompanied by the changes to the corresponding neuroanatomical structure that mediates olfactory perception.

    • Brian G Dias
    • Kerry J Ressler
  • The authors show, in mice, that maternal tumor necrosis factor-α (TNFα) genotype affects postnatal phenotypes in adult offspring. Lack of either one or two copies of the Tnf gene in dams led to reduced levels of chemokines in their milk, increased levels of adult hippocampal neurogenesis and improved spatial memory in offspring.

    • Bingfang Liu
    • Bojana Zupan
    • Miklos Toth
  • This study examines neuronal activity coupling between the medial prefrontal cortex (mPFC), basolateral amygdala (BLA) and hippocampus during the recall phase of a differential fear conditioning task and during exposure to a novel open field. The authors show that theta frequency power and synchrony between the mPFC and BLA increase with successful discrimination of aversive versus safe cues, and that the mPFC activity leads that in the BLA during safety.

    • Ekaterina Likhtik
    • Joseph M Stujenske
    • Joshua A Gordon
  • In this study, Mainland and colleagues de-orphan 18 human odorant receptors and find that 68% of these receptors exhibit polymorphisms that affect their function in vitro. They also show that the polymorphisms in one these odorant receptors, OR10G4, affect odor intensity and valence perception thus linking the molecular functioning of a single odorant receptor to human olfactory perception.

    • Joel D Mainland
    • Andreas Keller
    • Hiroaki Matsunami
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  • In this Resource, the authors generate a genome-wide methylation profile of DNA from the normal-appearing white matter of control and multiple sclerosis–affected brains and find subtle, but widely distributed, differences. In particular, they report that hypermethylated genes that regulate oligodendrocyte survival are also transcriptionally downregulated.

    • Jimmy L Huynh
    • Paras Garg
    • Patrizia Casaccia
  • Microglia are resident myeloid cells of the central nervous system integral for neuroprotective and neurodegenerative processes. Here the authors describe a unique TGF-β dependent molecular and functional microglia signature that distinguishes these cells from other immune and glial cells in the periphery and brain.

    • Oleg Butovsky
    • Mark P Jedrychowski
    • Howard L Weiner
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