Articles in 2015

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.

Mesolimbic dopamine has been implicated both in reward prediction and in promoting movement. This study demonstrates that the patterns of dopamine release in the nucleus accumbens core are shaped by the initiation of appropriate reward-guided actions and prospective response accuracy, and not just prediction errors.

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.

Previous work has suggested that cortical recurrent circuits can self-sustain their activity without thalamic input. A study now demonstrates that this is not the case in the awake brain, which tightly locks cortical timing to thalamic activity.

Synaptic plasticity during learning is as fundamental as it is hard to study. The underlying synaptic plasticity rule has now been inferred using only the firing rate statistics of visual neurons in monkeys before and after learning.

Previous studies have reported 'preplay' of hippocampal neural activity patterns associated with events yet to occur. Silva et al. challenge this finding on the basis of large-scale recordings before and after experiences.

The largest survey of gene expression ever performed in the adult human brain reveals highly stereotyped transcriptional patterning across individuals. The most stably patterned genes are enriched for neuronal annotations, disease associations, drug targets and correspond to resting state functional networks.

Neurons receive synaptic input primarily onto their dendrites. This review focuses on how synaptic inputs are integrated by dendrites, with an emphasis on recent work in the intact brain. It describes the range of computations dendrites perform on their inputs, highlighting their critical role in information processing in the brain.

Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding precisely how these variants contribute to disease will require a deeper appreciation for the mechanisms of gene regulation in the developing and adult human brain. The PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains, as well as functionally characterize disease-associated regulatory elements and variants in model systems. We are beginning with a focus on autism spectrum disorder, bipolar disorder and schizophrenia, and expect that this knowledge will apply to a wide variety of psychiatric disorders. This paper outlines the motivation and design of PsychENCODE.