Volume 17 Issue 12, December 2014

A randomized clinical trial in older adults shows that high dietary intake of cocoa flavanols enhances memory performance on an object-recognition task and neural activity as assessed by functional magnetic resonance imaging in the dentate gyrus of the hippocampus, a region that is critical for learning and memory.

Patch-clamp recordings and imaging in retina show that electrical synapses between dendrites of neighboring ganglion cells transform spatial patterns of light activated synaptic input into a temporal population code.

A study now provides proof of concept that restoration of Ras-Erk signaling during adulthood rescues cellular and cognitive phenotypes in mouse models of the genetic disorder Noonan syndrome.

A study links transient activation of the brain's reward system during a novel experience to frequent reactivation of memory traces during sleep and shows that artificial activation of the reward circuit can strengthen memories.

A study demonstrates that learning different character sets produces a repeatable arrangement of distinct cortical modules, suggesting that a preexisting cortical architecture is repurposed during learning.

In this Review, Lüscher and Lüthi draw some parallels between anxiety and addiction disorders as diseases of the brain's emotional valence system. The authors present an update on the anatomy and heterogeneity of the fear and reward circuitries, analyze our understanding of the synaptic and cellular mechanisms thought to underlie the two conditions and discuss recent studies causally linking the resulting circuit dysfunctions and alterations in behavior.

The amygdala is known to play an important role in fear conditioning. In this Review, the authors discuss extended circuits beyond the amygdala mediating fear learning and expression, focusing on the neural coding mechanisms underlying these behaviors.

Synaptic remodeling in the brain is dependent on the extracellular matrix remodeling mediated by zinc-dependent matrix metalloproteinases (MMPs). Using a rodent model, this study shows that the activity of MMP2 and 9 are differentially increased in the brain region nucleus accumbens after withdrawal from self-administered cocaine, during cue-induced relapse. Along with a similar response following relapse to other drugs of abuse, the study also shows that the increased MMP activity was needed for both relapse behavior and relapse-associated synaptic plasticity that included changes to the glutamate-mediated currents and dendritic spine head diameter.

In this study, the authors show that optogenetic photostimulation of dopaminergic (DA) neurons in the ventral tegmental area during exploration can enhance subsequent sharp wave/ripple-mediated reactivation of spatial memory. These results suggest that midbrain DA neurons are key mediators of hippocampal-dependent memory persistence.

Primate cortex can be organized with specialization and hierarchical principles, but presently there is little evidence for how it is organized temporally. Across six separate datasets, the authors find a hierarchical ordering of intrinsic fluctuation of spiking activity, with timescales that increase from sensory to prefrontal areas.

Previous work has suggested that the scaffolding protein ankyrin G is essential for the clustering of Na⁺ channels at the nodes of Ranvier. However, in this study, the authors show that, in the absence of ankyrin G, the complex of ankyrin R and βI spectrin can mediate Na⁺ channel clustering at the nodes.

In this study, the authors show that the scaffolding proteins ankyrin B and ankyrin G are expressed by Schwann cells and oligodendrocytes, respectively, and are enriched on the glial membrane at paranodal junctions where they interact with neurofascin 155. In addition, they find that ankyrins in oligodendrocytes have key roles in rapid and efficient paranode formation in the CNS.

Neuregulin 1 (NRG1) type III is a key mediator of Schwann cell development and myelination and is known to undergo proteolytic cleavage to produce an intracellular fragment. In this study, the authors show that this intracellular fragment of NRG1 modulates myelination by inducing the expression of a prostaglandin synthase (L-PGDS) which, in turn, leads to prostaglandin production and activation of GPR44.

The authors show that mice lacking Fragile X Mental Retardation Protein (FMRP) have disrupted neuronal migration during cortical development. FMRP-deficient mice also show altered excitatory-to-inhibitory balance early postnatally. They identify N-cadherin as a target of FMRP and show that re-expressing N-cadherin can rescue these phenotypes in FMRP-deficient mice.

Fragile X Syndrome (FXS) patients and the mouse model of the disease are known to have increased neocortical network excitability and hypersensitivity to sensory stimuli. The current study describes dendritic ion channel dysfunction to underlie sensory hypersensitivity in the FXS mouse model, particularly due to the reduction and dysfunction of dendritic h- and BK_Ca channels. The study also shows pharmacological rescue of cortical hyperexcitability using BK_Ca channel openers.

It has been suggested that astrocytes play a role in the onset and progression of neurodegenerative disorders such as ALS. In this study, the authors show that α-adducin forms a complex with α2-Na+/K+ ATPase in mutant SOD1-bearing astrocytes and that this interaction is necessary for the non-cell autonomous toxicity that induces muscle denervation, motor neuron death and decreased mortality.

The authors selectively modify chromatin in a specific gene in vivo to examine the link between chromatin dynamics and drug- and stress-evoked responses. They report that histone methylation or acetylation at the FosB locus in nucleus accumbens is sufficient to control drug- and stress-evoked transcriptional and behavioral responses.

In vertebrate vision, the two types of photoreceptors, rods and cones, operate under low and bright light intensities, respectively. Here the authors show that under bright light conditions, when rods are not sensing light, they act as relay cells for cone-driven surround inhibition.

Noonan syndrome (NS) is an autosomal dominant genetic disease that is co-morbid with cognitive deficits in a subset of patients. Using mouse models of NS, a study now shows that the synaptic plasticity and memory deficits in mouse models of NS are due primarily to the dysfunction in the MEK-Erk kinase pathways, and pharmacological intervention that alters MEK-Ras function can alleviate physiological and behavioral deficits in the mouse models of NS.

The counter-regulatory response (CRR) restores blood glucose levels after hypoglycemia. The authors identify a population of leptin receptor– and cholecystokinin-expressing neurons in the parabrachial nucleus of the hypothalamus that modulates the CRR. These neurons are activated by hypoglycemia, inhibited by leptin and project to the ventromedial hypothalamus.

Corticotropin-releasing factor (CRF) and dopamine (DA) are critical for stress and motivation, respectively. The authors show that CRF is synthesized in DA neurons and released in the ventral tegmental area, where it affects GABAergic inputs to DA neurons and mediates the motivational effects of nicotine withdrawal and escalation of nicotine intake.

Fine-scale synchrony of neural activity determines the nature of neural coding, but its underlying mechanisms are unclear. Here the authors find that coincident electrical and chemical synaptic inputs are nonlinearly integrated in overlapping retinal ganglion cell dendrites to produce synchronous spiking.

The authors report that in mice, the cerebellum modulates the activity of the striatum via a disynaptic pathway to facilitate optimal motor control. Dysfunction of this pathway can contribute to dystonia.

Training macaque monkeys with distinct sets of shapes resulted in novel domain formation in inferotemporal cortex. The localization of these domains was similar across monkeys, regardless of set-training order. The stereotyped location of the training-induced domains suggests a pre-existing architecture, and the authors explored various possible proto-architectures.

The many different behaviors mediated by the posterior parietal cortex (PPC) could arise from distinct specialized categories of neurons or from a single population of PPC neurons that is leveraged in different ways. The authors test this by studying rat PPC neurons during tasks involving multisensory decisions and conclude that a single network of neurons can support different behavioral demands.

Shohamy and colleagues found that administration of a placebo can enhance learning from positive outcomes in Parkinson disease's patients. An analysis of fMRI signals recorded during behavior indicated that the drug and placebo both enhanced the representation of expected value in the ventromedial prefrontal cortex and attenuated prediction error signals in the ventral striatum. These results suggest that the mere expectation of reward can drive learning.

This study provides causal evidence demonstrating that consuming a high flavanol diet improves dentate gyrus function and dentate gyrus–dependent cognitive functions in aged humans.

This Resource article provides detailed expression data from the striatum and cerebral cortex of early prenatal human samples, ranging in age from 2 to 20 weeks post-conception. Using a number of different analyses, the authors describe the transcriptional, spatio-temporal expression and functional profile that distinguish human striatal from neocortical neurons while also elucidating some differences between human and mouse striatal development.

The authors report an optical method involving simultaneous stimulation of single neurons using a red-shifted optogenetic probe and recording of population activity using a green fluorescent calcium sensor. They use this technique to manipulate individual place cells in CA1 during spatial navigation in a virtual reality environment.

Lecoq and colleagues introduce a two-photon microscope with two articulated arms that can image nearly any two brain regions, nearby or distant, simultaneously. They validate this new system by imaging calcium signals in two visual cortical areas in behaving mice, and find evidence suggesting activity fluctuations can propagate between cortical areas

In this paper, Atasoy and colleagues use a genetically-encoded synaptic marker for electron microscopy (GESEM) to probe long-range neuronal connectivity at the nanoscale level. The authors fused the horseradish peroxidase to the vesicle-associated membrane protein 2 (VAMP2) to label synaptic vesicles. Focusing on the mouse feeding system, they show that this new tool is suitable for connectomics analyses of genetically defined populations of neurons.