Articles in 2016

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.

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.

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.

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.

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.

The authors describe a glutamatergic septoentorhinal pathway that provides running-speed-correlated input to MEC layer 2/3. The speed signal is integrated by several MEC cell classes and converted into speed-dependent output. This speed circuit may be important for the spatial computations of MEC neurons.

Auditory hair cells contain mechanotransduction channels that are activated by sound. The authors show that Piezo2, a mechanotransduction channel important for touch perception, is expressed in auditory hair cells. Surprisingly, Piezo2 is not the mechanotransduction channel essential for auditory perception and is instead observed after damage to hair cells.

Hunger-promoting AgRP neurons and satiety-promoting POMC neurons in the arcuate nucleus mediate homeostatic regulation of hunger. Yet a rapidly acting satiety component analogous to rapidly hunger-promoting AgRP neurons has been missing. The authors identify this missing satiety signal and show that it is carried by a novel subset of arcuate glutamatergic neurons.

The authors show that a direct pathway from the dorsal hippocampus to the prelimbic cortex is necessary for contextual fear memory strengthening. Molecular analyses and functional targeting revealed that prelimbic excitatory and inhibitory synapses have a critical role in promoting memory strengthening, while inhibiting extinction.

The strength of aversive learning is proportional to the intensity of aversive experiences, but how brain circuits set memory strength during learning is not known. The authors show that an amygdala-to-midbrain feedback circuit conveying information about future unpleasant experiences inhibits aversive processing during learning to calibrate memory strength.

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.

Animals have a remarkable ability to adjust their behavioral response to the same stimulus based on the immediate behavioral context. The authors show that the nucleus basalis broadcasts a contextual signal to the auditory cortex that is then translated by inhibitory networks to regulate excitatory neuronal output and behavior.

The activity of cortical neurons is extremely noisy. This study builds a mathematical theory linking the spatial scales of cortical wiring to how noise is generated and distributed over a population of neurons. Predictions from the theory are validated using population recordings in primate visual area V1.

Self-movement estimation is critical to motor control and navigation; however, the neural circuits that accurately track body motion are poorly understood. This study shows that Drosophila optic-flow-processing neurons receive three distinct locomotor-related signals that are used to encode a quantitative estimate of the fly's walking movements, even in the absence of visual stimuli.

Previous work on mammalian motor cortex has focused on the role of this region in movement generation. Here the authors demonstrate that activity of vibrissa motor cortex neurons decreases during various forms of vibrissal touch, suggesting that a primary function of vibrissa motor cortex is to suppress whisking 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.

Recent technological advancements in the study of neural circuits provide reasons to be optimistic that novel treatments for psychiatric illnesses are just around the corner. Maximizing the chances of translating these advancements into real improvements in patient care requires a carefully considered road map.

Refined social phenotyping of syndromic and idiopathic forms of autism, combined with advances in genetics, animal models of syndromes and brain imaging, may facilitate discovery of shared brain mechanisms that will lead to new treatments. The reversal of social deficits in animal models is promising for eventual translation into therapeutics.

Recent models studying loss of the mouse homolog of the autism-associated gene CHD8 show altered Wnt signaling, cell fate and proliferation. How do these findings shape our understanding of this disease?

An obsession with producing and validating models (face, construct, predictive validity) has led many of us down a deep rabbit hole, thinking about models instead of mechanisms. Advances in the human genetics and neurobiology of brain disorders create exciting new opportunities, but only if we can get back to basics.