Articles in 2017

Touch-evoked dynamic mechanical pain is one of most bothersome and prevalent symptoms in chronic pain patients. Here the authors have genetically identified a population of spinal excitatory neurons that contribute to this form of pain. These cells process information from low-threshold Aβ mechanoreceptors and are part of a morphine-resistant pathway.

Little is known about the mechanisms underlying the orchestration of competing motivational drives. During the simultaneous presentation of cues associated with shock or sucrose, when rats may engage in fear- or reward-related behaviors, amygdala neurons projecting to prefrontal cortex more accurately predict behavioral output and bias animals toward fear-related behavior.

Wolff and colleagues show that ‘activity-silent’ brain states are important to working memory. Using a perturbation method to ‘ping’ the brain, they uncover hidden neural states that reflect temporary information held in mind and predict memory performance. They argue that dynamic hidden states could underpin working memory.

Microglia can expand and divide quickly in the context of CNS pathology, but little is known about the kinetics and clonality of microgliosis. Prinz and colleagues develop a new fate mapping system to monitor microglial dynamics. Microglial self-renewal is found to be a stochastic process under steady state conditions, whereas clonal expansion is observed during disease.

The authors report that genetic disruption of the connectivity of CCK⁺ basket cells during development reveals a critical role for these interneurons in the regulation of theta oscillatory activity and in the coding of spatial information in the adult mouse hippocampus.

The authors optogenetically suppressed CA1 pyramidal neurons during awake sharp-wave ripples (SPW-R) as mice were learning reward locations in a multiwell maze. Comparison of place cells’ activities before and after SPW-R manipulation suggests that interference with SPW-R-associated activity during learning prevents stabilization and refinement of the hippocampal map.

The authors show that during sleep, dreaming and specific perceptual dream contents can be localized to a posterior hot zone of the brain. By monitoring activity in this zone, they were able to predict dreaming in real time with high accuracy.

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.

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.

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.

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.

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.

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.

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.

Fear-related disorders are thought to reflect strong and persistent fear associations. The authors show that optogenetic high-frequency stimulation of direct amygdala inputs to the prefrontal cortex can destabilize fear memories and facilitate the extinction of previously acquired fear associations.

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.

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.

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.

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.

Entorhinal cortex transfers multimodal information to hippocampus CA1 neurons via indirect and direct pathways. The authors show that excitatory projections from lateral entorhinal cortex selectively target a subpopulation of morphologically complex, calbindin-expressing pyramidal cells in CA1, forming a distinct direct circuit that is required for olfactory associative learning.