Research articles

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.