Volume 17 Issue 9, September 2014

Two independent epigenome-wide association studies of Alzheimer's disease cohorts have identified overlapping methylation signals in four loci, ANK1, RPL13, RHBDF2 and CDH23, not previously associated with Alzheimer's disease. These studies also suggest that epigenetic changes contribute more to Alzheimer's disease than expected.

Polyglutamine expansion in the androgen receptor, causing X-linked spinal and bulbar muscular atrophy, impairs its function as a transcriptional coactivator regulating an extensive network of proteins involved in protein clearance.

In this issue, Shenhav et al. critically evaluate the idea that neural correlates of value actually represent value. They describe how, in many situations, value correlates can reflect other cognitive factors, such as decisional difficulty.

Olfaction has often been described as a 'synthetic' sense. A study now reveals a surprising capacity to resolve individual odorants in complex mixtures, with implications for how the nervous system recognizes objects.

In this review, the authors discuss the role of the lateral habenula in processing reward, both in the healthy brain and in models of depression, drawing on work in non-human primates and rodents.

The authors report that increased promoter methylation of the serotonin transporter gene predicts increased threat-related amygdala reactivity and decreased mRNA expression in postmortem amygdala tissue. This provides converging evidence for epigenetic regulation of behaviorally and clinically relevant human brain function.

Aging can lead to cognitive decline associated with neural pathology and Alzheimer's disease (AD). Here the authors scan the methylation status of CpGs across the entire genome of brain samples from aged subjects in an epigenome-wide association study (EWAS). Several loci, including ANK1, were associated with AD pathology, gene expression and AD genetic risk networks.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline. Here the authors describe an epigenome-wide association study (EWAS) of human post-mortem brain samples across multiple independent AD cohorts. They find consistent hypermethylation of the ANK1 gene associated with neuropathology.

In this study, the authors show that Celsr3 and Fzd3 interact in motor neurons to cooperatively direct axon guidance to target muscles in the periphery. In addition, they find that loss of Celsr3 or Fzd3 function also impairs axonal responses to ephrinA reverse, attractive signaling, suggesting a functional interaction between these guidance pathways.

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder that results from a polyglutamine repeat expansion in the androgen receptor (polyQ-AR). In this study, the authors show that autophagy is dysregulated in SBMA mice and in neural precursors obtained from iPSCs derived from human patients and that this results from an impaired interaction between AR and the transcription factor TFEB.

In this study, the authors show that age-related aberrant synaptic remodeling in the retinal outer plexiform layer is mediated by LBK1-AMPK signaling. They also show that treatments which elevate AMPK signaling, including caloric restriction or administration of metformin, can ameliorate these deficits.

Repeated cocaine exposure enhances excitatory connections onto medium spiny neurons (MSNs) in the nucleus accumbens (NAc). The authors show that cocaine selectively increases basolateral amygdala inputs onto direct pathway MSNs in the NAc medial shell. Inhibiting amygdala activity prevents this plasticity and blocks the increase in spine density on these neurons.

The authors recorded spontaneous and odor-evoked activity in the olfactory bulb of anesthetized and awake mice and found that distinct populations of interneurons independently orchestrated theta and gamma activity in this system. In particular, they found that silencing granule cells did not affect slow, odor-evoked inhibition.

Using a combination of targeted activation and optogenetic-based mapping in mice, this study demonstrates that sleep-active GABAergic neurons in the medullary parafacial zone promote slow wave sleep and cortical slow wave activity and uncovers functional circuit connections linking these neurons with the cortex.

Being able to perceive an individual odor in a continually changing and rich olfactory environment is a challenging task. Here, Rokni and colleagues find that this olfactory cocktail party problem can be studied in mice and reveal that the ability to identify a specific odor in a complex odorous scene is constrained by the amount of overlap in the representations of target and background odors at the level of olfactory receptors.

The authors identify a region in the cerebellar cortex where sensory and motor information from the neocortex converge. Activation of this region modifies activity in the motor cortex along with ongoing whisker movement parameters, demonstrating that such sensorimotor cortico-cerebellar loops are important for the fine control of movement.

The amygdala central nucleus (CEA) has been implicated in feeding control, but its role is controversial. The lateral subdivision of CEA (CEl) contains a subpopulation of GABAergic neurons, marked by protein kinase C-δ. In this paper the authors provide data suggesting that CEl PKC-δ+ neurons constitute an important node that mediates the influence of multiple anorexigenic signals.

While changes in dACC activity have traditionally been associated with variability in decision difficulty, a recent high-profile study has suggested that dACC instead encodes the value of foraging. In this study, the authors challenge this previous finding by showing that, when foraging value and decision difficulty are effectively dissociated, dACC activity corresponds to changes in choice difficulty.

It has been suggested that working memory representations of visual features are encoded by neurons in the areas of the early visual cortex. In this study, the authors show that sustained spiking activity in the macaque during a delayed match-to-sample task is actually absent from the middle temporal area but is instead observed in the medial superior temporal region and the lateral prefrontal cortex.

By integrating longitudinal and cross-sectional data from children, adolescents and adults, this functional magnetic resonance imaging study finds that a developmental transition to more efficient, memory-based problem-solving skills is accompanied by significant changes in hippocampal activation, functional connectivity with prefrontal-parietal circuits and interproblem representational stability.

In determining punishment, an actor's mental state often trumps the impact of emotions, as unintended harms may go unpunished, regardless of their magnitude. Using fMRI, the authors reveal a temporoparietal-medial-prefrontal circuit that regulates amygdala activity and by which evaluation of a transgressor's mental state gates our emotional urges to punish.

In this resource, the authors provide a comprehensive map of the thalamocortical projections in the mouse brain. To do this, they employed 254 highly overlapping injections of viral vectors to label and characterize long-range projections. Using this map as a framework, the authors determine the functionality of a subset of these connections via expression and activation of channelrhodopsin.