Innocuous mechanical stimuli, such as rubbing or stroking the skin, relieve itch through the activation of low-threshold mechanoreceptors. However, the mechanisms behind this inhibition remain unknown. We presently investigated whether stroking the skin reduces the responses of superficial dorsal horn neurons to pruritogens in male C57BL/6J mice. Single-unit recordings revealed that neuronal responses to chloroquine were enhanced during skin stroking, and this was followed by suppression of firing below baseline levels after the termination of stroking. Most of these neurons additionally responded to capsaicin. Stroking did not suppress neuronal responses to capsaicin, indicating state-dependent inhibition. Vesicular glutamate transporter 3 (VGLUT3)-lineage sensory nerves compose a subset of low-threshold mechanoreceptors. Stroking-related inhibition of neuronal responses to chloroquine was diminished by optogenetic inhibition of VGLUT3-lineage sensory nerves in male and female Vglut3-cre / NpHR-EYFP mice....

Stroke causes remodeling of vasculature surrounding the infarct, but whether and how vascular remodeling contributes to recovery are unclear. We established an approach to monitor and compare changes in vascular structure and blood flow with high spatiotemporal precision after photothrombotic infarcts in motor cortex using longitudinal 2-photon and multiexposure speckle imaging in mice of both sexes. A spatially graded pattern of vascular structural remodeling in peri-infarct cortex unfolded over the first 2 weeks after stroke, characterized by vessel loss and formation, and selective stabilization of a subset of new vessels. This vascular structural plasticity was coincident with transient activation of transcriptional programs relevant for vascular remodeling, reestablishment of peri-infarct blood flow, and large improvements in motor performance. Local vascular plasticity was strongly predictive of restoration of blood flow, which was in turn predictive of behavioral recovery. These findings reveal the ...

To define the importance of iron storage in oligodendrocyte development and function, the ferritin heavy subunit (Fth) was specifically deleted in oligodendroglial cells. Blocking Fth synthesis in Sox10 or NG2-positive oligodendrocytes during the first or the third postnatal week significantly reduces oligodendrocyte iron storage and maturation. The brain of Fth KO animals presented an important decrease in the expression of myelin proteins and a substantial reduction in the percentage of myelinated axons. This hypomyelination was accompanied by a decline in the number of myelinating oligodendrocytes and with a reduction in proliferating oligodendrocyte progenitor cells (OPCs). Importantly, deleting Fth in Sox10-positive oligodendroglial cells after postnatal day 60 has no effect on myelin production and/or oligodendrocyte quantities. We also tested the capacity of Fth-deficient OPCs to remyelinate the adult brain in the cuprizone model of myelin injury and repair. Fth deletion in NG2-positive OPCs signifi...

Theta-band (∼6 Hz) rhythmic activity within and over the medial PFC (“midfrontal theta”) has been identified as a distinctive signature of “response conflict,” the competition between multiple actions when only one action is goal-relevant. Midfrontal theta is traditionally conceptualized and analyzed under the assumption that it is a unitary signature of conflict that can be uniquely identified at one electrode (typically FCz). Here we recorded simultaneous MEG and EEG (total of 328 sensors) in 9 human subjects (7 female) and applied a feature-guided multivariate source-separation decomposition to determine whether conflict-related midfrontal theta is a unitary or multidimensional feature of the data. For each subject, a generalized eigendecomposition yielded spatial filters (components) that maximized the ratio between theta and broadband activity. Components were retained based on significance thresholding and midfrontal EEG topography. All of the subjects individually exhibited multiple (mean 5.89, SD 2...

In the article “Promiscuous G-Protein-Coupled Receptor Inhibition of Transient Receptor Potential Melastatin 3 Ion Channels by Gβγ Subunits,” by Omar Alkhatib, Robson da Costa, Clive Gentry, Talisia Quallo, Stuart Bevan, and David A. Andersson, which appeared on pages [7840–7852][1] of the

Oligodendrocyte (OL) progenitor cells (OPCs) are generated, proliferate, migrate, and differentiate in the developing brain. Although the development of OPCs is prerequisite for normal brain function, the molecular mechanisms regulating their development in the neocortex are not fully understood. Several molecules regulate the tangential distribution of OPCs in the developing neocortex, but the cue molecule(s) that regulate their radial distribution remains unknown. Here, we demonstrate that the secreted glycoprotein Reelin suppresses the proliferation of OPCs and acts as a repellent for their migration in vitro . These functions rely on the binding of Reelin to its receptors and on the signal transduction involving the intracellular protein Dab1. In the late embryonic neocortex of mice with attenuated Reelin signaling [i.e., Reelin heterozygote-deficient, Dab1 heterozygote-deficient mutant, or very low-density lipoprotein receptor (VLDLR)-deficient mice], the number of OPCs increased and their distributio...

The perception of duration in the subsecond range has been hypothesized to be mediated by the population response of duration-sensitive units, each tuned to a preferred duration. One line of support for this hypothesis comes from neuroimaging studies showing that cortical regions, such as in parietal cortex exhibit duration tuning. It remains unclear whether this representation is based on the physical duration of the sensory input or the subjective duration, a question that is important given that our perception of the passage of time is often not veridical, but rather, biased by various contextual factors. Here we used fMRI to examine the neural correlates of subjective time perception in human participants. To manipulate perceived duration while holding physical duration constant, we used an adaptation method, in which, before judging the duration of a test stimulus, the participants were exposed to a train of adapting stimuli of a fixed duration. Behaviorally, this procedure produced a pronounced negat...

Band ratio measures, computed as the ratio of power between two frequency bands, are a common analysis measure in neuro-electrophysiological recordings. Band ratio measures are typically interpreted as reflecting quantitative measures of periodic, or oscillatory, activity. This assumes that the measure reflects relative powers of distinct periodic components that are well captured by predefined frequency ranges. However, electrophysiological signals contain periodic components and a 1/f-like aperiodic component, the latter of which contributes power across all frequencies. Here, we investigate whether band ratio measures truly reflect oscillatory power differences, and/or to what extent ratios may instead reflect other periodic changes—such as in center frequency or bandwidth—and/or aperiodic activity. In simulation, we investigate how band ratio measures relate to changes in multiple spectral features, and show how multiple periodic and aperiodic features influence band ratio measures. We validate these f...

Synaptic ribbons are thought to provide vesicles for continuous release in some retinal nonspiking neurons, yet recent studies indicate that genetic removal of the ribbon has little effect on release kinetics. To investigate vesicle replenishment at synaptic ribbons, we used total internal reflection fluorescence microscopy to image synaptic vesicles and ribbons in retinal bipolar cells of goldfish ( Carassius auratus ) of both sexes. Analysis of vesicles released by trains of 30 ms depolarizations revealed that most releasable vesicles reside within 300 nm of the ribbon center. A single 30 ms step to 0 mV was sufficient to deplete the membrane-proximal vesicle pool, while triggering rapid stepwise movements of distal vesicles along the ribbon and toward the plasma membrane. Replenishment only becomes rate-limiting for recovery from paired-pulse depression for interstimulus intervals shorter than 250 ms. For longer interstimulus intervals, vesicle movement down the ribbon is fast enough to replenish releas...