Volume 19 Issue 12, December 2016

Intellectual disabilities and associated neurodevelopmental disorders may result from rare genetic mutations. Ganna et al. show that these also help explain variability in educational attainment, a proxy for cognitive function.

During synaptic activation, the function of astrocyte endfeet depends on the vascular target: at the capillary, but not at the arteriole, a newly described P2X1R–phospholipase D2 pathway modulates prostaglandin E2 release and vessel dilation.

Humans and animals can collect and maintain information that guides decisions, but how neural circuits achieve this is unknown. It seems neural populations may do so by passing through diverse states in many possible sequences.

Recent experiments suggest that dishonesty can escalate from small levels to ever-larger ones along a 'slippery slope'. Activity in bilateral amygdala tracks this gradual adaptation to repeated acts of self-serving dishonesty.

The ventromedial prefrontal cortex is attributed with various functions during valuation, affect regulation and social cognition. Nature Neuroscience asked a moderator to lead researchers in a dialogue on shared and distinct viewpoints of this region's roles.

Functional studies of neuronal assemblies that encode memories have progressed dramatically due to recent technological advances. This review shows how a focus on assembly formation and consolidation provides a powerful conceptual framework to relate mechanistic studies of synaptic, neuronal and circuit plasticity to behaviorally relevant aspects of learning and memory.

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.

The authors describe neurons in the macaque anterior thalamus tuned to pitch and roll orientation relative to gravity, independently of visual landmarks. Individual cells exhibit two-dimensional tuning curves peaking at a preferred vertical orientation. These results identify a thalamic pathway for gravity cues to influence three-dimensional spatial orientation.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

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.

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.

Experimental autoimmune encephalomyelitis can be induced by strong activation of innate immunity. This subtype of EAE is resistant to interferon (IFN)-β treatment and is NLRP3 inflammasome independent. Its development is dependent upon lymphotoxin-β receptor LTβR and CXCR2, and can be inhibited by blocking these receptors. The IFNβ-resistant EAE subtype is characterized by minimal remission and neuronal damage induced by semaphorin-6B on CD4⁺ T cells.

In this study, Sivadasan et al. show that the interactome of the C9ORF72 protein contains cofilin and other actin-binding proteins. They also demonstrate that actin dynamics are reduced in patient-derived motor neurons and tissues with ALS-related intronic expansion of the C9ORF72 gene, leading to altered axon growth and growth cone dynamics.

Active neurons increase their energy supply by dilating nearby arterioles and capillaries to increase blood flow, but the mechanisms underlying neurovascular coupling are debated. In this paper, the authors show that different calcium-dependent signaling pathways regulate blood flow at the level of capillary pericytes and arteriole smooth muscle.

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.

The authors identify two genetic markers defining non-overlapping populations of principal cells in the amygdala that respond to stimuli of opposite valence. These two populations of cells contribute to behavioral responses to aversive or rewarding experiences, are distributed along antero-posterior gradients that run in opposite directions, and synaptically suppress each other.

During tactile exploration, neural activity related to movement of digits or whiskers is suppressed to facilitate high signal-to-noise ratio encoding of touch. The authors show that in mouse this computation occurs in layer 4 of the barrel cortex and is mediated by fast-spiking interneurons.

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.

Sleep rearranges the firing patterns of excitatory projection neurons in zebra finch songbirds. Patterned inhibition is implicated in maintaining stable songs in spite of the instability in the projection neuron population.

The authors developed experimental and computational approaches to study moment-to-moment changes in the activity of populations of cortical neurons as mice accumulated evidence during decision-making in virtual reality. They propose that evidence accumulation may not require winner-take-all competitions but instead emerges from general dynamical properties that instantiate short-term memory.

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.

In neuronal cultures, synaptic strengths scale with the network size to preserve balance between excitation and inhibition, maintain variable spiking statistics and reduce correlations in spiking as predicted by theory and observed in the intact brain.

The biological mechanisms underlying memory are complex and typically involve multiple molecular processes operating on timescales ranging from fractions of a second to years. The authors show using a mathematical model of synaptic plasticity and consolidation that this complexity can help explain the formidable memory capacity of biological systems.

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.

Resting-state functional connectivity has helped reveal the brain's network organization, yet its relevance to cognitive task activations has been unclear. The authors found that estimating activity flow over resting-state networks allows prediction of held-out activations, suggesting activity flow as a linking mechanism between resting-state networks and cognitive task activations.

In this paper, the authors show that dishonesty gradually increases with repetition. This escalation is supported by a reduction in response to self-serving dishonesty over time in the amygdala.

Top-down control is important for sensory processing. In this study, the authors used virus-assisted circuit mapping to identify the brain networks for top-down modulation of multiple sensory modalities and the subnetworks within the visual network, thus providing an anatomical foundation for understanding the brain mechanisms underlying top-down control of behavior.

The ability to target and manipulate specific neuronal populations is crucial for understanding brain function. In this report, the authors describe a novel virus that restricts gene expression to telencephalic GABAergic interneurons, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in mice and in non-genetically tractable species.