Volume 16 Issue 10, October 2013

High-grade glioblastomas survive glucose-poor environments by becoming more stem cell–like. Increased glucose uptake by the transporter Glut3, a new biomarker of poor clinical outcome, drives this enhanced malignant progression.

A study reveals that SIRPα is released from postsynaptic neurons to induce and mature their synaptic inputs, using CD47 as the presynaptic receptor. SIRPα is cleaved in an activity-dependent manner to act as retrograde signal.

Gupta et al. report in this issue that, in Drosophila melanogaster, a dietary supplement of spermidine—a polyamine originally isolated from semen—protects against cognitive aging by acting through the autophagic pathway.

The ability to categorize objects depending on task demands is critical. A primate study finds that the prefrontal cortex signals to the parietal cortex during categorization, indicating an asymmetric, top-down interaction.

Using in vivo imaging of layer V pyramidal neurons in the dorsomedial frontal cortex of mice, the authors show that cocaine administration rapidly increases the formation and accumulation of dendritic spines. These spine changes correlate with conditioned place preference for cocaine, but not with cocaine-induced locomotor activity.

The authors find that white matter–derived OPCs differentiate with similar efficiencies whether they are engrafted into white matter or gray matter, while gray matter–derived OPCs only differentiate with high efficiency when placed in white matter. This suggests that there are intrinsic differences between OPCs depending on their site of origin.

Brain tumor initiating cells (BTICs) are self-renewing, tumorigenic cells that often reside in a necrotic and hypoxic niche in the brain. Here the authors show that BTICs can become more tumorigenic upon glucose restriction and compensate for this cellular stress by upregulating their capacity to take up glucose.

Fused-in-Sarcoma (FUS) gene encodes an RNA/DNA binding protein whose mutations are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This study shows that FUS functions in the neuronal DNA damage response by its recruitment to the site of DNA double-stranded breaks and by its interaction with histone deacetylase 1. The study also shows ALS/FTLD-associated mutant FUS is defective in DNA repair mechanism and that ALS/FTLD patients with FUS mutations have greater DNA damage.

In this study, the authors show that overexpression/accumulation of the parkin substrate AIMP2 induces an age-dependent degeneration of dopaminergic neurons and results in motor dysfunction. This effect is dependent on AIMP2-induced activation of PARP1, which, in turn, induces cell death via parthanatos.

In this study, the authors show that depletion of the IL-17 signaling component, Act1, specifically from NG2⁺ glia led to a substantial reduction in the severity of pathology in an EAE mouse model. They also find that IL-17 induces apoptosis of NG2⁺ cells in an Act1-dependent manner.

Using two-color uncaging of glutamate and GABA in rat hippocampal slices, the authors show that appropriately timed activation of dendritic GABA_A and glutamate receptors promotes spine shrinkage and elimination. These effects spread locally to adjacent spines, involve NMDA receptors and the recruitment of calcium nanodomains, and can compete with spine enlargement in an ADF/cofilin-dependent manner.

In this study, the authors document how SIRPα, a cell-adhesion molecule, participates in the late maturation of hippocampal excitatory synapses. They find that in response to activity, SIRPα sheds its ectodomain, which acts presynaptically to promote maturation in a process that requires CaM kinase, matrix metalloproteinases and the presynaptic receptor CD47.

Using voltage sensitive–dye imaging in the cortices of anesthetized and awake mice, the authors show that spontaneous activity patterns contain similar motifs as those evoked by sensory stimulation. These motifs are also seen after optogenetic activation of the cortex, and they correlate with structural connectivity.

The authors show that extinction of fear conditioning lowers the threshold for synaptic potentiation in the lateral amygdala (LA), and fear renewal-inducing stimuli induce phosphorylation of AMPAR subunit GluA1 at serine 831 in LA. Infusion of a peptide competing with Ser831-phosphorylated GluA1 into the LA blocks this low-threshold potentiation and attenuates fear renewal.

This study shows that associative reward learning produces dynamic experience-dependent alterations in DNA methylation and immediate-early gene expression in ventral tegmental area (VTA) dopamine neurons and that DNA methylation in the VTA is required for the formation of new reward-related memories.

Polyamines such as spermidine and putrescine are known to promote autophagy and longevity in fruit flies. Similar to many other organisms, Drosophila also display age-induced memory impairment. Here, Gupta et al. find that a decrease in brain polyamines in aging Drosophila is correlated with age-dependent memory impairment. They also find that polyamines in flies' diet can alleviate this impairment, demonstrating a link between polyamines, autophagy and memory decline.

The authors describe a sensory context–dependent switch in a salt sensory circuit in C. elegans. In response to large changes in salt concentration, the ASE sensory neuron releases insulin-like peptides that switch the AWC olfactory sensory neuron into an interneuron in the salt circuit. Disrupting insulin signaling interferes with attraction to high concentrations of salt.

The authors show that long-term exposure of Drosophila to camphor, which is normally repulsive, leads to decreased repulsion. They identify the TRPL channel as the probable receptor for camphor in gustatory neurons and show that downregulation of TRPL, which requires the E3 ubiquitin ligase Ube3a, underlies this change in taste preference.

Here the authors combine computational modeling, voltage-sensitive dye imaging (VSDI) in behaving monkeys, and behavioral measurements in humans, to investigate whether the large-scale topography of V1 population responses influences shape judgments. They find the judgments of human observers were systematically distorted as had been predicted based on the VSDI responses in monkey V1.

To examine the nature of information encoded by prefrontal output signals, the authors simultaneously recorded neuronal activity in monkey prefrontal and parietal cortices during a rule-based spatial categorization task. They found that signals reflecting rule-dependent categories were selectively transmitted from prefrontal to parietal neurons.

This study used fMRI repetition suppression to demonstrate that human subjects can represent and evaluate novel choice options by invoking multiple memories for previous experiences in hippocampus and medial prefrontal cortex.

In this technical report, the authors describe a new, red-shifted variant of channelrhodopsin (called red-activatable channelrhodopsin or ReaChR) that shows faster kinetics and greater photocurrents than currently available red-shifted probes. In addition, they show that ReaChR can be activated in awake mice through the intact skull.