Articles in 2015

The authors measured the orientation tuning of ∼28,000 thalamic boutons and ∼4,000 neurons in layers 1–5 of awake mouse V1. With adaptive optics allowing accurate measurement of deep tissue activity, around half of the boutons in layer 4 were found to carry orientation and direction information.

GABA_B receptors are the most abundant inhibitory G protein–coupled receptors in the mammalian brain. Using high-resolution proteomics, the authors show that native GABA_B receptors are macromolecular complexes with previously unknown complexity in subunit composition. This molecular diversity in structure and assembly encodes the diversity of GABA_B physiology in the CNS.

Impairment of cognitive function is a common feature of many neurodevelopmental disorders. Systems genetics analysis in the brain uncovered a convergent gene network for both cognition and neurodevelopmental disorders. As the network does not recapitulate known pathways, this finding represents a new basis for understanding factors influencing normal and disordered cognition.

The authors identify a new arousal circuit in the mammalian brain. They provide correlative and optogenetic evidence indicating that a subset of hypothalamic cells drive awakening from non-rapid eye movement (slow-wave) sleep and emergence from anesthesia by exerting a strong inhibitory tone onto reticular thalamic neurons.

The authors used two-photon imaging to measure the orientation tuning of thalamic boutons and neurons in mouse V1. They found that a smaller fraction of thalamic boutons in layer 4 than in superficial cortical layers carried orientation and direction information.

Current models of active vision emphasize the role of intracortical feedback projections. The authors report that thalamocortical projections, in particular from the higher order lateral posterior nucleus, provide an alternative pathway by which contextual sensory and motor information, as well as putative visuomotor error signals, are conveyed to primary visual cortex.

Learning and memory processes require experience-dependent changes in chromatin modifications. Here the authors provide a detailed view of the gene regulatory roles of DNA methylation and histone modifications during the acquisition and maintenance of memory across different cell types and brain regions.

Oligodendrocyte death in the DTA mouse model leads to a fatal, secondary demyelinating disease associated with CNS T cell infiltration and myelin antigen-specific T cells in lymphoid organs, which can transfer a mild neurological disease to naive mice, indicating that oligodendrocyte death is sufficient to trigger an adaptive autoimmune response against myelin. These results suggest that the disease-initiating event in the autoimmune disorder multiple sclerosis may occur within the CNS.

This study found that both the anterolateral (AL) and middle-lateral (ML) belt regions of the primate auditory cortex encoded acoustic stimulus features used to solve an auditory decision task. However, only AL activity was modulated by behavior and causally contributed sensory evidence to form the decision.

Language consists of a hierarchy of linguistic units: words, phrases and sentences. The authors explore whether and how these abstract linguistic units are represented in the brain during speech comprehension. They find that cortical rhythms track the timescales of these linguistic units, revealing a hierarchy of neural processing timescales underlying internal construction of hierarchical linguistic structure.

Amyloid-β (Aβ) is generated by BACE-1-mediated cleavage of amyloid precursor protein (APP), and its deposition is a pathological hallmark of Alzheimer's disease. The authors find that APP and BACE-1 interact in biosynthetic and endocytic compartments in neurons. In axons, APP and BACE-1 interact during cotransport. The Alzheimer's disease–protective Icelandic mutation attenuates these interactions, suggesting a mechanism of protection.

Sensory cortex spiking is well known to predict trial-to-trial variability in perceptual choice, but the origins of this choice-related activity are not fully understood. In the mouse somatosensory system, electrophysiology, imaging and optogenetic experiments reveal a progression of choice-related activity as touch signals flow from primary afferents to cortex.

Phasic changes in dopamine activity correlate with prediction error signaling. But causal evidence that these brief changes in firing actually drive associative learning is rare. Here the authors show that brief pauses in dopamine neuron firing at the time of reward mimic the effects of endogenous negative prediction errors.

The authors show that peripheral nerve injury induces de novo expression of colony-stimulating factor 1 (CSF1) in the injured sensory and motoneurons. CSF1, transported through axons, acts on its receptor on spinal cord microglia, inducing microglia proliferation and DAP12-dependent upregulation of pain-related microglial genes, eventually leading to neuropathic pain.

DNA methylation in human brain shows dramatic variation across development. Genetic loci implicated in risk for schizophrenia are enriched for epigenetic states that show changes from the transition from prenatal to postnatal life. These findings suggest that early development is involved in both genetic and environmental risk factors for schizophrenia.

There are widespread genetic effects on DNA methylation in the developing brain. Fetal brain mQTLs are enriched in regulatory domains, overlapping with variants influencing gene expression. Most are developmentally stable, but some are fetal specific. These mQTLs are enriched in genomic regions associated with schizophrenia, a neuropsychiatric disorder with neurodevelopmental origins.

Seeking insight into dopamine's contribution to motivation and learning, the authors examined dopamine release in the rat nucleus accumbens during adaptive decision-making. Dopamine levels convey a running estimate of available future reward, which is used to decide whether it's worthwhile to engage in a behavioral task. Abrupt fluctuations serve as reward prediction errors, reinforcing behavioral choices.

Although attentional abilities vary widely and have profound everyday effects, a standardized measure of these abilities is lacking. This study introduces a new fMRI measure based on patterns of whole-brain connectivity, which predicts adults' attention performance and children's ADHD symptoms from data acquired while individuals are resting in the scanner.

The c-fos gene is induced by a broad range of stimuli and is commonly used as a reliable marker for neural activity. The authors demonstrate that the combinatorial activation of multiple enhancers surrounding the c-fos gene is a critical mechanism of ensuring robust c-fos gene induction in response to various stimuli.

This study examines the effect of categorization-task training on parietal (PPC) and prefrontal (PFC) activity and finds a learning-dependent emergence of memory-related delay activity in PPC, whereas PFC shows delay-period selectivity both before and after categorization training. This reveals distinct roles of PFC and PPC in short-term working memory.