Sensory information is conveyed by populations of neurons, and coding strategies cannot always be deduced when considering individual neurons. Moreover, information coding depends on the number of neurons available and on the composition of the population when multiple classes with different response properties are available. Here, we study population coding in human tactile afferents by employing a recently developed simulator of mechanoreceptor firing activity. First, we highlight the interplay of afferents within each class. We demonstrate that the optimal afferent density to convey maximal information depends on both the tactile feature under consideration and the afferent class. Second, we find that information is spread across different classes for all tactile features and that each class encodes both redundant and complementary information with respect to the other afferent classes. Specifically, combining information from multiple afferent classes improves information transmission and is often more efficient than increasing the density of afferents from the same class. Finally, we examine the importance of temporal and spatial contributions, respectively, to the joint spatiotemporal code. On average, destroying temporal information is more destructive than removing spatial information, but the importance of either depends on the stimulus feature analysed. Overall, our results suggest that both optimal afferent innervation densities and the composition of the population depend in complex ways on the tactile features in question, potentially accounting for the variety in which tactile peripheral populations are assembled in different regions across the body.

Information theory provides a popular and principled framework for the analysis of neural data. It allows to uncover in an assumption-free way how neurons encode and transmit information, capturing both linear and non-linear coding mechanisms and including the information carried by interactions of any order. To facilitate its application, here we present Neuroscience Information Toolbox (NIT), a new toolbox for the accurate information theoretical analysis of neural data. NIT contains widely used tools such as limited sampling bias corrections and discretization of neural probabilities for the calculation of stimulus coding in low-dimensional representation of neural activity (e.g. Local Field Potentials or the activity of small neural population).Importantly, it adds a range of recent tools for quantifying information encoding by large populations of neurons or brain areas, for the directed transmission of information between neurons or areas, and for the calculation of Partial Information Decompositions to quantify the behavioral relevance of neural information and the synergy and redundancy among neurons and brain areas. Further, because information theoretic algorithms have been previously validated mainly with electrophysiological recordings, here we used realistic simulations and analysis of real data to study how to optimally apply information theory to the analysis of two-photon calcium imaging data, which are particularly challenging due to their lower signal-to-noise and temporal resolution. We also included algorithms (based on parametric and non-parametric copulas) to compute robustly information specifically with analog signals such as calcium traces. We provide indications on how to best process calcium imaging traces and to apply NIT depending on the type of calcium indicator, imaging frame rate and firing rate levels. In sum, NIT provides a toolbox for the comprehensive and effective information theoretic analysis of all kinds of neural data, including calcium imaging.

Punctate palmoplantar keratodermas (PPPKs) are characterized by circumscribed hyperkeratotic lesions on palms and soles. These genodermatoses exhibit both clinical and genetic heterogeneity. By applying whole exome sequencing to a Scottish kindred with autosomal dominant PPPK (OMIM #148600), we identified a heterozygous heterozygous nonsense mutation in AAGAB, encoding alpha-and gamma-adaptin binding protein p34. This gene is located within a previously reported PPPK locus on chromosome 15q22. Conventional sequencing identified a further 7 heterozygous loss-of-function mutations in 17 additional families with severe or mild forms of PPPK. The p34 polypeptide has a GTPase domain related to the Rab superfamily of vesicle transport proteins and was shown biochemically to bind both alpha-and gamma-adaptins, indicative of a role in vesicle biology. Ultrastuctural analysis of lesional epidermis confirmed abnormalities of intracellular vesicle populations. Immunohistochemistry showed hyperproliferative basal cells within the punctate lesions. RNAi knockdown of p34 in keratinocytes led to increased cell division and a marked increase in epidermal growth factor receptor (EGFR) protein, as well as alterations in the abundance and/or phosphorylation of a number of downstream signaling molecules. We hypothesize that p34 deficiency impairs endocytic recycling of EGFR, leading to a hyperproliferative form of hyperkeratosis due to increased EGFR signaling. Impaired epithelial differentiation of induced pluripotent stem cells from EEC ectodermal dysplasia patients is rescued by a small compound APR-246/PRIMA-1METR Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem cell deficiency. In this study, we designed a novel cellular model that recapitulated major embryonic defects related to EEC. Fibroblasts from healthy donors and EEC patients carrying two different point mutations in the DNA binding domain of p63 were reprogrammed into induced pluripotent stem cell (iPSC) lines. EEC-iPSC from both patients showed early ectodermal commitment into K18+ progenitor cells but failed to further properly differentiate into K14+ cells (epidermis/limbus) or K3/K12+ cells (corneal epithelium). APR-246 (PRIMA-1MET), a small compound that restores functionality of mutant p53 in human tumor cells, could revert corneal epithelial lineage commitment and reinstate normal p63related signaling pathway. This study illustrates the relevance of iPSC for p63-related disorders. This unique model serves to characterize the abnormal molecular circuitry of this congenital disease and paves the way for future therapy of EEC. During development, multipotent progenitor cells establish tissue-specific programmes of gene expression that underlie a proces...