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Using two-color two-photon calcium imaging, the authors identified transformations of representations across synaptically connected pairs of neurons along a visual pathway to the Drosophila central complex. Neural responses to stimuli in the ipsilateral field are modulated by stimuli in the contralateral field, an effect that depends on past stimulus history.
Noxious thermal and mechanical stimuli have to be faithfully detected and avoided to ensure survival. In this study, the authors uncover a modality-specific circuit responsible specifically for mechanonociceptive behavior in Drosophila. They show that the escape response to mechanical but not thermal noxious stimuli requires multisensory integration by mechanosensory neurons and neuromodulatory feedback signaling.
Aberrant EGFR signaling is common in glioblastoma. The authors show that inhibiting EGFR leads to increased secretion of TNF and activation of a survival pathway in cancer cells. A combined inhibition of EGFR and TNF signaling inhibits tumor growth in a mouse model, suggesting a new treatment for patients with glioblastoma.
Most cancer patients experience loss of appetite and feelings of illness, which contribute to cancer-related deaths and morbidity. The authors demonstrate that, in mice, activation of a subset of neurons in the parabrachial nucleus mediate cancer-induced anorexia and associated sickness behaviors.
To unravel structural regularities in neocortical networks, Gal et al. analyzed a biologically constrained model of a neocortical microcircuit. Using extended graph theory, they found multiple cell-type-specific wiring features, including small-word and rich-club topologies that might contribute to the large repertoire of computations performed by the neocortex.
The authors demonstrate that decisions for reward can have more a complicated dependence on past experiences than previously believed. Previous models describe decisions as influenced by rewards received in similar situations. Here the authors show that experiences that share only incidental features can also reemerge to bias present choices.
Attention changes correlations between neuronal responses. In this study, Verhoef and Maunsell use multielectrode recordings in monkeys to reveal a link between normalization mechanisms, correlated neuronal activity and attention. The findings show that normalization mechanisms shape response correlations and that these correlations change when attention biases normalization mechanisms.
The authors find that mammalian acid-sensing taste receptor cells, previously shown to be putative sour taste sensors, also mediate responses to water. Optogenetic activation of this population of cells in thirsty mice induced robust drinking response in the absence of water. This study shows that acid-sensing TRCs contribute to the detection of water in the oral cavity.
The authors monitored neuronal activity in mouse visual cortex during visual-motion stimulation and perturbed retinal direction selectivity. After perturbation, the proportion of posterior-motion-preferring cortical cells decreased, and their response at higher stimulus speeds was reduced. Thus, functionally distinct, retina-dependent and retina-independent computations of visual motion exist in mouse cortex.
The authors provide evidence that a cerebellum-like structure at the initial stage of mammalian auditory processing (the dorsal cochlear nucleus) functions to cancel out self-generated sounds. A similar function has been established for cerebellum-like structures in electroreceptive fish, suggesting a conserved function for these structures across vertebrates.
The authors identify programmed cell death ligand-1 (PD-L1), an immunity suppressor produced by cancer cells, as a new pain inhibitor and a neuromodulator. They report that PD-L1 is produced by melanoma and normal neural tissues and that it inhibits acute and chronic pain. Via activation of PD-1, its receptor, PD-L1 decreases the excitability of nociceptive neurons in mouse and human dorsal root ganglia.
Brain function relies on flexible communication between cortical regions. It has been proposed that changing patterns of oscillatory coherence underlie information routing. However, oscillations in vivo are very irregular. This study shows that short-lived and stochastic oscillatory bursts coordinate across areas to selectively modulate interareal communication.
The authors show that in a mouse model of spinal muscular atrophy (SMA), there is a reduction in sensory synaptic drive that leads to motor neuron dysfunction and motor behavior impairments. SMA motor neurons showed a lower surface expression of Kv2.1 potassium channels and reduced spiking ability. Increasing neuronal activity pharmacologically led to the normalization of Kv2.1 surface expression and an improvement in motor function.
Although vocal learning is widely speculated to depend on motor to auditory (i.e., forward) pathways, the neurons that convey forward signals important to vocal learning remain unknown. Here the authors identify neurons that transmit signals from songbird motor to auditory regions and demonstrate their role in vocal learning.
The authors establish a critical role for somatostatin interneurons in visually induced gamma oscillations in the primary visual cortex of mice. Optogenetic manipulations in awake animals, combined with an innovative computational model with multiple interneuron subtypes, provide a mechanism for the synchronization of neural firing across the retinotopic map.
The external globus pallidus (GPe) is a key contributor to motor suppressing pathways in the basal ganglia. The authors show that optogenetic interventions targeted to specific neuronal subpopulations in the GPe can disrupt pathological activity in the basal ganglia and restore movement for hours beyond stimulation.
Using pathway-specific optogenetic inhibition, the authors demonstrate that projections from the mediodorsal thalamus to prefrontal cortex support the maintenance of working memory, while prefrontal–thalamic projections support subsequent choice selection. Thalamo–prefrontal projections have a circuit-specific role in sustaining prefrontal delay-period activity, a neuronal signature required for successful task performance.
Bower et al. describe a population of mural lymphatic endothelial cells found along meningeal blood vessels in the adult zebrafish. These mural cells are distinct from meningeal lymphatic vessel cells but form by developmental lymphangiogenesis. They take up low-density lipoproteins from the bloodstream and can modulate angiogenesis during meningeal vascularization.
Crockett et al. used model-based fMRI to investigate the neural basis of decisions to profit from harming others vs. themselves. Most people preferred to harm themselves over others for profit. This moral preference was associated with diminished neural responses in value-sensitive brain regions to profit gained from harming others.
Using calcium imaging and optogenetic manipulation in mice performing a working memory task, the authors show that delay activity in prefrontal cortex pyramidal neurons is crucial for task performance. Optogenetic activation of VIP interneurons enhances the neuronal representation of task-relevant information and improves the animal's memory retention.