Research articles

De novo mutations in CHD8 are associated with autism spectrum disorder, but the basic biology of CHD8 remains poorly understood. Here the authors find that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice.

Using whole-exome sequencing, the authors identified 244,246 coding-sequence and splice-site ultra-rare variants (URVs) and found that gene-disruptive and putatively protein-damaging URVs were significantly more abundant in schizophrenia cases than in controls. The excess of protein-compromising URVs was concentrated in brain-specific genes, particularly in neuronally expressed genes whose proteins are located at the synapse.

Rare genetic mutations that disrupt the functionality of important genes increase the risk of psychiatric and neurodevelopmental disorder. This study found that, in the general population not diagnosed with such disorders, these same mutations affect the average educational level. Carriers of these mutations have on average half a semester less of education than noncarriers.

Loss of Hdac1 and Hdac2 in adult brain is detrimental to neuronal survival and triggers dysregulation of Sapap3 in the striatum in a MeCP2-dependent manner that results in an exacerbated repetitive behavior phenotype.

The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of subjects with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, they found that ∼20% of schizophrenia loci have variants that may contribute to altered gene expression and liability.

The UK Biobank combines detailed phenotyping and genotyping with tracking of long-term health outcomes in a large cohort. This study describes the recently launched brain-imaging component that will ultimately scan 100,000 individuals. Results from the first 5,000 subjects are reported, including thousands of associations, population modes and hypothesis-driven results.

The ability to estimate environmental state under limited sensory observation is essential for many behaviors and can be realized using dynamic Bayesian inference. The authors use in vivo two-photon calcium imaging and probabilistic population decoding to show that cortical neurons implement prediction and updating, the fundamental features of dynamic Bayesian inference.

AgRP neurons of the arcuate nucleus of the hypothalamus promote homeostatic feeding yet are rapidly suppressed by food-related sensory cues. The authors identify a population of inhibitory DMH-LepR neurons that relays real-time information about the nature and availability of food to dynamically modulate ARC-AgRP neuron activity and feeding behavior.

Much of what is known about nervous system development is based on chemical signaling. In this study, Koser et al. demonstrate that developing neurons also respond to mechanical signals and that local tissue stiffness is a regulator of neuronal growth in vivo.

The authors find that activity in rodent visual cortex can depend on the animal's location in a virtual environment and can predict upcoming visual stimuli. Omitting a stimulus that a mouse expects to see results in a strong mismatch signal, implying that visual cortex compares visual signals to expectations in familiar environments.

The authors demonstrate that attention slowly fluctuates at a rhythm that resembles resting-state oscillations. During periods of attention, the brain aligns its neuronal oscillations and the cortical operations they orchestrate to the timing of external stimuli, while attentional lapses are characterized by operations aligned to internally timed alpha oscillations.

The healthy human brain is a mosaic of varied genomes. Using a single cell sequencing approach targeting L1 elements, the authors show that the contribution of L1 to somatic mosaicism goes beyond retrotransposition and includes deletion of genomic regions associated with L1.

Motivated behaviors are critically dependent upon arousal but little is known about the neuronal mechanisms that coordinate motivational processes with sleep–wake regulation. The authors demonstrate that VTA dopaminergic neurons, which are central regulators of motivational processes, bidirectionally regulate sleep–wake states and sleep-related nesting behavior.

The authors uncovered a pathway from the lateral amygdala to the auditory cortex (ACx) of mice that is essential for auditory fear memory retrieval. Simultaneous imaging of pre- and postsynaptic structures in ACx in vivo revealed an increased rate of synapse formation in this pathway after auditory fear conditioning.

Chen et al. found that Foxp2 interacts with Mef2c to wire synaptic circuits linking neocortex to basal ganglia. The study analyzes the basics of circuit wiring underlying vocal communication.

The authors performed genome-wide microRNA (miRNA) expression profiling in post-mortem brains from individuals with autism spectrum disorder (ASD) and controls, and identified miRNAs and co-regulated modules perturbed in ASD.

A core aspect of human episodic memory is the ability to recall events in the order that they were experienced. The authors found that successful memory for order is related to the precise timing of high frequency brain activity with respect to slower underlying rhythms.

The sympathetic system maintains a physiological balance, adjusts bodily functions during daily living activities, and can activate stress responses. The authors identify a variety of unique sympathetic neuronal types and show that the system is highly organized with dedicated neurons organized into discrete outflow channels for specific bodily functions.

The authors show that hypothalamic neurons that synthesize tyrosine hydroxylase regulate food intake and body weight. By a combination of dopamine and GABA release, these neurons modulate the activity of both pro-opiomelanocortin neurons and paraventricular nucleus neurons that also contribute to energy homeostasis.

Polycomb repressive complex 2 (PRC2) is a key mammalian epigenetic regulator that supports neuron specification during development. In this paper, the authors find that PRC2 plays a role in the survival of adult neurons. The loss of PRC2 activity in adult striatum led to the de-repression of multiple genes with bivalent histone methylation marks and to a fatal neurodegeneration phenotype.