Articles in 2016

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.

Coupling distances between synaptic vesicles and Ca²⁺ channels determine the efficacy of neurotransmission. Böhme et al. find that presynaptic scaffold complexes spatiotemporally control Unc13 isoforms to establish two independent release pathways at subsynaptic active zones: Unc13B defines nascent, loosely coupled synapses whereas Unc13A facilitates release at mature synapses by tight coupling between Ca²⁺ channels and synaptic vesicles.

The authors find that the portion of rat somatosensory cortex representing the trident whiskers—a set of whiskers specialized for ground contact during exploration—encodes information about speed and acceleration of the animal. Microstimulation of this area alters running speed, consistent with the idea that trident whiskers and their neural representation could serve as a tactile speedometer.

Before children can read, their brains have yet to develop selective responses to words. This study demonstrates that a child's connectivity pattern at age 5 can predict where their own word-selective cortex will later develop. This suggests that connectivity lays the groundwork for later functional development of cortex.

The authors show that tau can be released by neurons and transferred to other neurons via the extracellular space. Moreover, they show that enhancing neuronal activity accelerates transneuronal tau propagation and exacerbates tau pathology.

The vesicular transporter VGAT controls GABA vesicle filling at inhibitory terminals. Here Meye et al. show that cocaine withdrawal reduces VGAT at synapses from pallidum to lateral habenula, thereby decreasing inhibitory transmission. This GABAergic synaptic plasticity is crucial for behaviors modeling cocaine-evoked aversive states and stress-induced relapse.

A combination of increased neural activity, induced by visual stimulation or using chemogenetics, and increasing mTOR signaling promotes retinal ganglion cell axon regeneration and partial recovery of visual behaviors after injury.

By studying a severe neuropathy in mice, Quintes, Brinkmann et al. demonstrate that the nuclear zinc-finger protein Zeb2 (Sip1) is essential for Schwann cell differentiation and myelin synthesis. Since Zeb2-deficient Schwann cells continuously express repressors of lineage progression, ‘inhibiting the inhibitors’ emerges as a new principle of peripheral myelination control.

In this study, Wilson et al. find that dendritic spines on neurons in the visual cortex cluster according to orientation preference. The degree of clustering on single neurons strongly predicts somatic orientation selectivity and the prevalence of local dendritic signals in the dendritic field, suggesting a role for dendritic computation in shaping orientation selectivity.

The authors show how dopamine neurons operate in the context of cholinergic transmission and find that the afferents originating from two functionally distinct (motor and limbic) cholinergic nuclei of the brainstem selectively modulate subsets of neurons in the ventral tegmental area.

Autism spectrum disorder is a complex disease with a strong genetic basis that remains under-characterized by current genetics studies. Here, the authors use a computational approach based on a human brain-specific gene network to predict autism-associated genes across the genome and further delineate their functional and developmental characteristics.

This study shows that the transcriptional regulator Zeb2 is required for the onset of peripheral myelination and remyelination. Zeb2 recruits HDAC1–HDAC2–NuRD co-repressor complexes to antagonize inhibitory effectors including Notch, while activating promyelinogenic factors. A Mowat-Wilson syndrome–associated ZEB2 mutation disrupting HDAC–NuRD interaction abolishes Zeb2 activity for Schwann cell differentiation.