Articles in 2013

The authors use in vivo imaging to examine astrocyte dynamics after a cortical injury over the course of several weeks. They reveal a heterogeneity in astrocyte responses and show that astrocytes do not migrate toward the injury site, but instead proliferate in the juxtavascular region.

The authors show that the strengthening of excitatory inputs onto nucleus accumbens D2 medium spiny neurons (D2-MSNs) correlates with a weak motivation to self-administer cocaine in mice. Silencing or activating D2-MSNs enhances or suppresses the motivation to self-administer cocaine, respectively, suggesting that this pathway constrains compulsive drug seeking behaviors.

In this study, the authors show that neuronal activity, induced by natural exploration, exposure to visual stimuli or optogenetic probe–mediated stimulation, can induce double-stranded DNA breaks (DSBs) in neurons. The numbers of these DSBs were aggravated in the presence of amyloid precursor protein and depended on extrasynaptic NMDAR activity.

In this study, the authors show that layer V projection neurons require the presence of subcortical CX3CR1-positive microglia for survival. IGF1 secretion from these microglia appears to be necessary for this trophic effect. Inhibition of the microglial cell activation abrogates IGF1 secretion and compromises neuronal survival.

Senescence degrades reward-based decision-making. Here the authors show that there are abnormalities in older adults in a functional magnetic resonance imaging measure of reward prediction error (RPE) signaling and changes in the structural connectivity of areas encoding reward value information. Administration of levodopa ameliorated behavioral deficits and restored RPE signaling in some older adults.

BAF53b is a neuron-specific component of the nucleosome remodeling complex mSWI/SNF that allows euchromatin formation and provides epigenetic regulation of gene expression. Here, the authors generated BAF53b mutant and rescue mice to show that postnatal nucleosome modeling is crucial to hippocampal synaptic plasticity, neuronal morphology and memory performance.

The authors performed a genome-wide RNAi screen for genes modifying mutant Huntingtin (mHTT) clearance, identifying NUB1 as a protein whose overexpression lowered mHTT protein amounts, rescued mHTT-induced neuronal death and improved motor function in a Drosophila model of Huntington's disease. NUB1 promoted polyubiquitination and proteasomal degradation of mHTT.

The endocannabinoid 2-AG is produced by the enzyme diacylglycerol lipase (DGL). The authors show that DGLα is phosphorylated and inhibited by calcium/calmodulin–dependent protein kinase II (CaMKII). Inhibition of CaMKII activity increases striatal DGL activity and basal 2-AG amounts, and augments short-term retrograde endocannabinoid signaling at striatal glutamatergic synapses.

The authors find that serotonin, acting through 5-HT_1B receptors, potentiates temporoammonic pathway–to–CA1 cell excitatory synapses in the hippocampus. Chronic unpredictable stress increased the magnitude of this potentiation, and chronic treatment with fluoxetine restored normal levels of this potentiation, a process that was required for the behavioral effects of chronic fluoxetine.

The brain selects stimuli for preferential processing on the basis of both their physical salience and their relevance to behavior. Recording from the midbrain of the barn owl, the authors show that a single inhibitory circuit is critical for both physical salience-driven (exogenous) and internally driven (endogenous) control of stimulus selection.

The authors show that reducing histone deacetylase 1 expression or activity in the nucleus accumbens increases global levels of histone acetylation but also increases histone methylation, leading to reduced cocaine-induced changes in behavior. This effect is mediated in part by decreased GABA_A receptor expression and decreased inhibitory tone on nucleus accumbens neurons.

This study shows that Parkinson's disease–associated mutant forms of leucine-rich repeat kinase 2 (LRRK2) impair chaperone-mediated autophagy in neurons, thereby reducing degradation of α-synuclein by this pathway and contributing to the accumulation of this protein observed in brain tissue from patients with Parkinson's disease.

Neurofibromatosis type 2 (NF2) is caused by inactivation of the NF2 gene, which encodes merlin. NF2 patients develop peripheral neuropathies. The authors show that NF2 inactivation decreases axonal integrity in mice and NF2 patient tissue. Their data suggest that merlin activates RhoA and promotes neurofilament heavy chain phosphorylation to maintain axonal integrity.

Memory and associated plasticity mechanisms span different timescales, from fleeting to enduring. This study shows that, across species, mTORC2's control of actin dynamics is critical for long-term forms of memory and synaptic plasticity.

Sensory signals are transduced at high resolution, but their structure must be stored in a more compact format. Here the authors show that the auditory system summarizes the temporal details of sounds using time-averaged statistics. Such statistical representations produce good categorical discrimination, but limit the ability to discern temporal detail.

In embryonic development, epithelial-mesenchymal transition (EMT) is the process whereby epithelial cells delaminate from the epithelial sheet and adopt a mesenchymal phenotype in cell motility and migration. This study shows that the Snail superfamily transcription factors Scratch 1 and 2 regulate an EMT-like process in newborn neurons derived from neuroepithelial cells in the developing mouse cortex. This process affects subsequent initiation of radial migration and ultimately neuronal cell positioning.

Trovò and colleagues find that aging is accompanied by a decrease in the levels of the phosphoinositide PI(4,5)P₂, PLCγ activity and the PI(4,5)P₂-clustering molecule MARCKS in mouse hippocampal synaptic membranes. Moreover, increasing MARCKS levels in old mice corrects some of the synaptic plasticity and memory deficits associated with aging.

Research on event perception has focused on transient elevations in predictive uncertainty or surprise as the primary signal driving event segmentation. Here the authors report behavioral and neuroimaging evidence that suggests that event representations can emerge even in the absence of such cues. They propose that this learning occurs in a manner analogous to the learning of semantic categories.

In this study, the authors show that, in newborn cortical neurons, the TrkB and TrkC receptors are transactivated by the EGF receptor, rather than by their traditional ligands, BDNF and NT-3. This transactivation appears to be involved in the migration of these neurons from the ventricular zone to the cortical plate.

To facilitate decisions between distinct options, goal values could be represented using a common currency. Here the authors find that a region of medial prefrontal cortex contains a distributed goal-value code that is independent of stimulus category. However, in the medial orbitofrontal cortex, they also find unique category-dependent distributed value codes.