Absence of meningeal mast cells in the Mitf mutant mouse.

Mast cells (MCs) are located in the meninges of the central nervous system (CNS), where they play key roles in the immune response. MC-deficient mice are advantageous in delineating the role of MCs in the immune response in vivo. In this study, we illustrate that a mutation in microphthalmia-associated transcription factor (Mitf) affects meningeal MC number in a dosage-dependent manner. C57BL/6J Mitf null mice lack meningeal MCs completely, whereas heterozygous mice have on average 25% fewer MCs. Mitf heterozygous mice might be a valuable tool to study the role of MCs in the meninges.

Alpha fluctuations regulate the accrual of visual information to awareness.

Endogenous brain processes play a paramount role in shaping up perceptual phenomenology. This is illustrated by the alternations experienced by humans (and other animals) when watching perceptually ambiguous, static images. We hypothesised that endogenous alpha fluctuations in the visual cortex pace the accumulation of sensory information leading to perceptual outcomes. Here, we addressed this hypothesis using binocular rivalry combined with visual entrainment and electroencephalography in humans (64 female, 53 male). The results revealed a correlation between the individual frequency of alpha oscillations in the occipital cortex and perceptual alternation rates experienced during binocular rivalry. In subsequent experiments we show that regulating endogenous brain activity via rhythmic entrainment produced corresponding changes in perceptual alternation rate. These changes were observed only in the alpha range but not at lower entrainment frequencies, and were much reduced when using arrhythmic stimulation. Additionally, entraining at frequencies above the alpha range did not result in speeding up perceptual alternation rates. Overall, these findings support the notion that visual information is accumulated via alpha cycles to promote the emergence of conscious perceptual representations. We suggest that models of binocular rivalry incorporating posterior alpha as a pacemaker can provide an important advance in the comprehension of the dynamics of visual awareness.

Prdm12 modulates pain-related behavior by remodeling gene expression in mature nociceptors.

ABSTRACT: Prdm12 is a conserved epigenetic transcriptional regulator that displays restricted expression in nociceptors of the developing peripheral nervous system. In mice, Prdm12 is required for the development of the entire nociceptive lineage. In humans, PRDM12 mutations cause congenital insensitivity to pain, likely because of the loss of nociceptors. Prdm12 expression is maintained in mature nociceptors suggesting a yet-to-be explored functional role in adults. Using Prdm12 inducible conditional knockout mouse models, we report that in adult nociceptors Prdm12 is no longer required for cell survival but continues to play a role in the transcriptional control of a network of genes, many of them encoding ion channels and receptors. We found that disruption of Prdm12 alters the excitability of dorsal root ganglion neurons in culture. Phenotypically, we observed that mice lacking Prdm12 exhibit normal responses to thermal and mechanical nociceptive stimuli but a reduced response to capsaicin and hypersensitivity to formalin-induced inflammatory pain. Together, our data indicate that Prdm12 regulates pain-related behavior in a complex way by modulating gene expression in adult nociceptors and controlling their excitability. The results encourage further studies to assess the potential of Prdm12 as a target for analgesic development.