Research articles

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.

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 show that chromatin of Hox genes is arranged in discrete domains. Patterning signals trigger recruitment of transcription factors to these domains, leading to rapid clearance of repressive histone methylation. This provides further insight into the transcriptional mechanisms underlying the establishment of epigenetically inherited rostrocaudal neuronal identity.

Persistent neural activity in the absence of a stimulus is a neural correlate of working memory, but the mechanism remains unknown. Here the authors use mathematical modeling to demonstrate a corrective-feedback mechanism for maintaining persistent activity based upon the inhibitory and excitatory microcircuitry of neocortical memory-storing regions.

How the cortex processes and transforms sensory input coming from the thalamus is still a matter of debate. Here the authors optogenetically silence local cortical circuits to show that intracortical excitation amplifies and prolongs thalamic inputs to the auditory cortex.

Mutations in the gene encoding the F-box domain–containing protein Fbxo7 are genetically associated to an autosomal recessive form of early-onset Parkinson's disease of similar severity to those caused by Parkinson's disease–linked mutations in the genes for the mitochondrial kinase PINK1 or the E3 ubiquitin ligase Parkin. Burchell et al. show that Fbxo7 acts in a common cellular and molecular pathway with Parkin and PINK1 in autophagic clearance of mitochondria in response to mitochondrial depolarization and damage.

Phosphorylation of the eukaryotic initiation factor 2 α subunit (eIF2α) is increased in the brains of Alzheimer's disease patients and model mice. Here the authors show that knocking down two kinases that phosphorylate eIF2α, PERK and GCN2, rescues protein synthesis, synaptic plasticity and behavioral deficits in Alzheimer's disease model mice.

Using optogenetics to silence the cortex, the authors show that thalamic inputs to layer 4 V1 neurons in anesthetized mice only contribute a third of the total excitation to these cells during presentation of visual stimuli. Moreover, they find that a small offset in the center of ON and OFF receptive subfields accounts for the orientation tuning of thalamic excitation to these cells.

By silencing intracortical excitation in mouse primary visual cortex, Li and colleagues find that the tuning of layer 4 pyramidal cells is independent of cortico-cortical inputs. Instead, intracortical excitation amplifies thalamocortical signals and expands the spatial receptive field of layer 4 neurons.

In this study, the authors show that all three major classes of GABAergic interneuron form distinct, tight clusters in the cortex. In addition, they find that this clustering effect is not strictly modulated by clonal origin, suggesting a role for local non-cell-autonomous cues.

Grid cell activity in the rodent and non-human primate entorhinal cortex is thought to provide spatial location information to the hippocampus for navigation and spatial processing. Here, Jacobs et al. examined single neuron spiking activities from human subjects performing a virtual spatial navigation task and show the presence of grid-like firing activity.

Enhancing endocannabinoid signaling is a potential therapeutic approach to treating anxiety disorders. Here the authors show that a compound leading to 'substrate-selective' inhibition of cyclooxygenase-2 (cox-2) increases endocannabinoid levels without affecting non-endocannabinoid lipids or prostaglandin synthesis. This compound decreased anxiety-like behaviors in mice via increased endocannabinoid signaling.

The authors use two-photon Ca²⁺ imaging of axonal boutons in hippocampal CA1 of behaving mice to monitor the activation of septo-hippocampal GABAergic boutons. They report that some sensory inputs are more effective than locomotion in driving firing by these long-range GABAergic projections.

By examining the genetic makeup of Northern Finnish sub-isolate populations, Stoll et al. show association between deletion of a topoisomerase III gene (TOP3B) and both schizophrenia and cognitive impairment. They also uncover a mechanism for the concomitant integration of TOP3β with the fragile X protein FMRP into messenger ribonucleoprotein complexes

By monitoring metabolic and neuronal activity in nonhuman primates after long-term training, Picard, Matsuzaka and Strick show that skill learning is correlated with a reduction in metabolic activity in the primary motor cortex without affecting neuronal firing. This suggests that skill learning results in an increase in the metabolic and synaptic efficiency in the motor cortex.

Topoisomerases are thought to work in DNA, but not RNA, metabolism. Here Xu et al. describe that Top3A can also act as an RNA topoisomerase and find it in a complex with the fragile X syndrome protein FMRP and a binding partner of FMRP, Tudor domain–containing protein 3 (TDRD3), which together promote synapse formation in flies and mice. These data suggest that topoisomerases are needed for both DNA and RNA metabolism.

The authors find that a fronto-parietal network's brain-wide functional connectivity pattern shifted more than other networks' across a variety of task states. Further, these connectivity patterns could be used to identify the current task, supporting a role for fronto-parietal regions in reconfiguring brain networks to flexibly implement task demands.

The Toll receptor superfamily has a role in innate immunity that arose early in evolution. Here the authors show that in fruit flies, Toll-6 and Toll-7 function in the CNS as receptors for the fly neurotrophins DNT1 and DNT2.

The authors investigate the mechanisms of long-term depression of inhibitory synapses onto medium spiny neurons in the striatum. They identify direct vs. indirect pathway-specific and state-dependent differences in endocannabinoid signaling mechanisms underlying this plasticity.

Although oxytocin is generally thought to exert anxiolytic, prosocial and antistress effects, reports of anxiogenic effects in humans have recently emerged. Here the authors show that oxytocin receptors in the lateral septum mediate the stress-induced enhancement of fear conditioning in mice in a process involving MAPK-ERK signaling.