Articles in 2013

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Attention alters neural responses that encode different aspects of visual stimuli, but exactly how these changes together modulate the encoded spatial representation of a scene remains unclear. Here the authors look at spatial priority maps of attended to and ignored stimuli and find that attention increases the gain but not the size of stimulus representations.

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.

The authors find that ACR-23, a ligand-gated cation channel of the cys-loop family, is a betaine receptor and is expressed in worm mechanosensory neurons involved in stimulating locomotion. Excessive activation of ACR-23 leads to paralysis and is responsible for the nematocidal properties of betaine. The authors also find that the action of betaine on ACR-23 is allosterically potentiated by the aminoacetonitrile derivative monepantel, a new antihelminthic drug.

Pyramidal cells have to integrate thousands of inputs across their expansive dendritic arbors. The spatial spread of these inputs should lead to intraneuronal propagation delays. Here the authors show that the distribution of HCN channels in hippocampal pyramidal cells normalizes these delays, particularly for inputs at theta and gamma frequencies.

Saha and colleagues measured the spatiotemporal dynamics of odor representations across populations of neurons in the locust olfactory system during the presentation of two overlapping odors. They report that the performance of locusts in a background-independent odor recognition task is correlated with the ability to decode foreground odor identity from the population activity, suggesting the existence of a background-invariant population code for odorants in this system.

This study shows that spontaneous opening of presynaptic voltage-gated calcium channels (VGCCs) is a major trigger of action potential independent synaptic vesicle release, and finds that R-type channels contribute disproportionately, consistent with a relatively negative activation threshold. The authors also use Ca²⁺ chelation experiments and computational modeling to reconcile how transient Ca²⁺ nanodomains evoked by VGCC opening trigger both spontaneous and action potential evoked neurotransmission.