Volume 20 Issue 5, May 2017

Capillary endothelial cells sense neuronal activity-evoked increases in extracellular K⁺ via K_IR2.1 inwardly rectifying K⁺ channels. The ensuing hyperpolarization travels upstream along the vascular network, reaching arterioles and evoking vasodilation.

Technical advances in calcium imaging enable the first tests of classic theories of cerebellar learning. Two independent groups reveal dense representation of surprising modalities in cerebellar granule cells.

A study combines monkey behavioral testing with electrical stimulation of face patches, located with functional MRI and studied electrophysiologically, to probe the behavioral relevance of the face patches' selectivity.

The consequences of spinal cord injury are often severe and irreversible; cell transplantation has emerged as a potential treatment. In this Review, the authors highlight mechanisms through which cell transplantation is thought to promote functional improvements and the obstacles to making cell transplantation a viable therapy.

The Huntington's disease (HD) induced pluripotent stem cell (iPSC) consortium describe the combined use of differentiated patient-derived iPSCs and systems biology to discover underlying mechanisms in HD. They identify neurodevelopmental deficits in HD cells that can be corrected in cells and in vivo with a small molecule.

Brain tumor initiating cells (BTICs) utilize high-affinity glucose uptake, which is normally active in neurons to maintain energy demands and self-renew. Leveraging metabolomic and genomic analyses, Wang et al. report that de novo purine biosynthesis reprograms BTIC metabolism, revealing a potential point of fragility amenable to targeted cancer therapy.

Regeneration of myelin is a dynamic, yet enigmatic process. Dombrowski et al. uncover a central role for regulatory T (T_reg) cells in driving oligodendrocyte differentiation, in part via CCN3, a novel factor in T_reg function and oligodendrocyte biology. This identifies T_reg cells as key cellular players in efficient remyelination.

The authors used knockout mice to demonstrate the normal function of the protein α-synuclein, which has a central role in Parkinson's and other neurodegenerative diseases. The presynaptic protein promoted dilation of the exocytotic fusion pore, and mutations that cause Parkinson's disease specifically impaired this normal function.

Relatively little is known about the mechanisms that preserve memories during long-term storage. The authors found that neural activation during learning triggers long-lasting transcription of a specific neurexin-1 splice isoform, enabling retention of hippocampus-dependent memory. This process was mediated by signaling through the AMPK pathway leading to histone modifications.

Acute stress elicits physiological and behavioral responses that enhance survival. This study in mice shows that stress reduces tissue injury in a model of renal ischemia-reperfusion injury by activating an anti-inflammatory response via the sympathetic system and the spleen. C1 neurons located in the brainstem mediate this protective effect of stress.

Nicotine has rewarding effects that motivate its consumption. In addition to these rewarding effects, nicotine also has aversive properties that motivate its avoidance. Here the authors identify a pathway in the brain that regulates nicotine avoidance. Adaptive responses in this and other aversion-related pathways may contribute to the development of tobacco addiction.

Longden et al. demonstrate that brain capillaries function as a vast sensory web, monitoring neuronal activity by sensing K⁺ and translating this into a K_IR-channel-mediated regenerative retrograde hyperpolarizing signal that propagates to upstream arterioles to drive vasodilation and an increase in blood flow into the capillary bed.

Granule cells constitute half of the cells in the brain, yet their activity during behavior is largely uncharacterized. The authors report that granule cells encode multisensory representations that evolve with learning into a predictive motor signal. This activity may help the cerebellum implement a forward model for action.

Learning to predict reward is thought to be driven by dopaminergic prediction errors, which reflect discrepancies between actual and expected value. Here the authors show that learning to predict neutral events is also driven by prediction errors and that such value-neutral associative learning is also likely mediated by dopaminergic error signals.

Scientists have long debated the extent to which different brain regions are specialized for specific tasks. Here the authors show that electrical microstimulation of face-selective brain regions in the temporal lobe of monkeys distorts the animal's percept not just of faces but also of certain non-face objects including round objects.

Pandya et al. describe a protocol to differentiate human and mouse iPSCs into cells with the phenotype, transcriptional profile and functional properties of microglia. The treatment of murine intracranial malignant gliomas with these cells demonstrates their potential clinical use. These microglia-like cells will enable further studies into the role of microglia in health and disease.