Articles in 2014

A study demonstrates that variability in how people perform a movement can predict the rate of motor learning on an individual basis. This suggests that motor 'noise' is a central component of motor learning.

Although projections from the insect antennal lobe to the mushroom body are probabilistic, those to the lateral horn are stereotyped, suggesting an interplay of preconfigured and plastic circuits in olfactory processing.

A study in this issue of Nature Neuroscience reports that administering caffeine to humans immediately after memory encoding enhances consolidation, as reflected by improved performance in a memory test a day later.

Nature Neuroscience presents a series of reviews highlighting recent progress in our understanding of the neurobiology of normal and pathological pain and itch.

New findings in preclinical Alzheimer's disease patients and mouse models of the disease suggest that it is the lateral, rather than the medial, entorhinal cortex that is most susceptible to tau pathology early in Alzheimer's disease. Aberrations begin here and spread to other cortical sites.

There is growing evidence for the existence of cross-talk between somatosensory labeled lines during the processing of noxious information, lending support to the notion that the nociceptive system operates under combinatorial encoding rules. In this Review, Prescott, Ma and De Koninck present an update on a controversy that is probably as old as the field of somatosensation itself and propose that the next step forward in our understanding of pain will necessarily involve the meticulous dissection of spinal dorsal horn microcircuitry.

Voltage-gated ion channels are key regulators of noxious signal transmission at the level of the periphery. In this Review, Zamponi and Waxman discuss recent advances in our understanding of the role of some of these channels in pain processing in primary afferent neurons, their dysfunction in congenital and acquired disease states and emerging possibilities for new analgesics.

In this Review, Piomelli and Sasso survey the functions of endogenous lipid mediators in the peripheral gating of nociceptive signals. They focus on the mechanisms and pathways associated with analgesic lipids, such as endocannabinoids, lipid amides, lipoxins and resolvins, and discuss their role in the interaction between nociceptive and immune systems in the context of pain.

What makes certain individuals more susceptible to developing chronic pain? In this article, Denk, McMahon and Tracey review our current knowledge of the genetic, epigenetic and other environmental factors that contribute to pain vulnerability or resilience and delineate the brain networks that are involved in chronic pain states.

Pain and itch are very distinct sensations that rely on both overlapping and orthogonal mechanisms in primary sensory afferents and in the spinal cord. In this article, Bautista, Wilson and Hoon review recent advances in our understanding of the molecular, cellular and circuit basis of acute and chronic itch in the peripheral and central nervous systems.

Using representational similarity analysis to link human MEG with human fMRI and monkey electrophysiological data, the authors provide an integrated temporal and spatial account of object categorization. Early, low-level processing corresponded to activity in primary visual cortex, while later object processing related to inferior temporal activity in a category-specific manner.

In this Technical Report, the authors describe a new methodology for rapid and flexible knockdown of specific proteins in vitro and in vivo—without the need for genetic modification of the target—using a small peptide construct that targets the protein of interest and marks it for chaperone-mediated autophagy.

The authors show that there is global loss of heterochromatin in tau transgenic Drosophila and mice, and post-mortem brain from Alzheimer's disease patients. Oxidative stress and DNA damage mechanistically link tau and heterochromatin loss. Finally, they show that reversing tau-induced heterochromatin loss reduces neurodegeneration in tau transgenic Drosophila.

The authors trained mice to perform rapid action sequences while recording from neurons in the direct and indirect basal ganglia pathways. In addition to neurons whose activity reflected the start or stop of a sequence, they identified neurons that displayed sustained activity or inhibition throughout an entire action sequence.

This study shows that early neonatal sensory deprivation of one modality can impact cortical plasticity of other sensory cortices because of the reduction in dendritic release of oxytocin from paraventricular hypothalamic neurons. The study also shows that exogenous oxytocin can attenuate the effects of neonatal sensory deprivation on cortical plasticity, thus mimicking the beneficial effects of enriched sensory exposure.

The authors show that leucine-rich repeat kinase 2 (Lrrk2) binds protein kinase A (PKA) regulatory subunit IIβ to decrease PKA activity in striatal projection neurons (SPNs). Lrrk2 regulation of PKA prevents its synaptic translocation, altering synaptogenesis and transmission in developing SPNs. A Parkinson's disease–associated mutant of Lrrk2 prevented its interaction with PKARIIβ.

This study shows that the memory deficit caused by amyloid fibrils in rodents is mediated, in part, by neuroinflammation leading to histone modification via alteration of the interaction between HDAC2 and methyl-CpG-binding protein 2 (MeCP2) and resulting epigenetic modification of the neuroligin 1 promoter, causing a reduction in neuroligin 1 expression in neurons.

The authors show that mice lacking one copy of gene encoding the transcription factor T-box brain 1 (TBR1) show deficient axonal projections from amygdala neurons, as well as social and cognitive behavioral deficits. Tbr1 haploinsufficiency alters expression of multiple Tbr1 target genes, and restoring their expression restores axon outgrowth defects in vivo.

The authors show that dopamine receptor 1 (D1)-expressing neurons in the medial prefrontal cortex (mPFC) of mice show increased activity in response to food intake. Using optogenetic stimulation and inhibition, they show that mPFC D1 neuron projections to the medial basolateral amygdala can increase or decrease food intake, respectively.