Our subjective experience of color is typically described by abstract properties such as hue, saturation, and brightness that do not directly correspond to sensory signals arising from cones in the retina. Along the hue dimension, certain colors-red, green, blue, and yellow-appear unique in that they are not perceived as a combination of other colors, and the pairs red-green and blue-yellow appear opposites. However, the anatomical and physiological correlates of these "unique hues" within the brain and the reason for their existence remain a mystery. Here, we demonstrate a direct connection between these hues and the statistics of the natural visual environment. Analysis of simulated cone responses on a dataset of 503 calibrated natural images reveals a strongly non-Gaussian distribution in 3D color space, with heavy tails in distinct, asymmetrically arranged directions. A sparse coding model is then adapted to this data so as to minimize the total sum of coefficients on the basis vectors for representing the data. A six-basis-vector model converges to the four unique hues in addition to black and white. Moreover, we find that the nonlinear nature of inference in the sparse coding model yields both excitatory and inhibitory interactions among latent variables; the former facilitates combining adjacent pairs of unique hues to encode intermediate hues situated between them, while the latter enforces mutual exclusivity between opposite unique hues. Together, these findings shed new light on the distribution of color in the natural environment and provide a linking principle between this structure and the phenomenology of color appearance.

Dry eye disease (DED) is a multifactorial ocular surface disorder for which effective therapeutic options remain limited. This study aimed to investigate the therapeutic effects of naringin (NAR) in DED and elucidate its underlying mechanisms. DED was induced by topical administration of 0.075% BAC twice daily for 7 days. During days 8-14, BAC administration was continued while mice received NAR eye drops Corneal epithelial integrity and tear secretion were evaluated using corneal fluorescein sodium staining and the phenol red cotton thread test, respectively. In parallel, an in vitro hyperosmotic stress model was constructed by exposing human corneal epithelial cells to hyperosmotic sodium chloride medium (90 mM). Inflammation, oxidative stress, apoptosis, and autophagy-related phenotypes and mechanisms were analyzed using real-time quantitative PCR, Western blot, flow cytometry, and immunofluorescence. NAR eye drops significantly alleviated ocular surface damage in DED mice, enhanced tear secretion, reduced corneal inflammatory factor expression, and increased conjunctival goblet cell density. Furthermore, NAR attenuated oxidative stress and apoptosis through the promotion of autophagic flux. Mechanistic investigations revealed that NAR downregulated the PI3K/AKT/mTOR signaling pathway, thereby enhancing autophagic flux, and that its anti-inflammatory and antioxidant effects are closely associated with the inhibition of this pathway. Collectively, these findings suggest that NAR represents a promising therapeutic candidate for DED, with its beneficial effects mediated through enhancing autophagic flux via the PI3K/AKT/mTOR pathway, leading to the alleviation of oxidative stress and ocular surface inflammation.

Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway have been tested in cluster headache with mixed results, and four systematic reviews and meta-analyses reached different conclusions, leaving clinicians without a clear answer on whether, and in whom, to use these drugs.

Sleep disturbances are frequently observed in patients with neurodegenerative diseases, but in vivo evidence linking subcortical sleep-wake structures to sleep phenotypes is limited. We aim to examine associations between MRI-derived measures of subcortical sleep-wake regulating regions and polysomnographic sleep parameters in individuals with Alzheimer's disease and cognitively healthy controls. Fifty-seven adults (45 with biomarker-confirmed Alzheimer's disease and 12 cognitively healthy controls with normal pTau217 plasma levels) were recruited at the Hospital Clínic de Barcelona. All participants completed overnight polysomnography and 3T brain MRI, including a neuromelanin-sensitive sequence. MRI-derived measures of wake-promoting structures [locus coeruleus (LC), posterior hypothalamus and basal forebrain] and sleep-promoting regions (anterior hypothalamus) were obtained. We estimated the association between nocturnal polysomnographic variables [including total sleep time, sleep efficiency, time in rapid eye movement (REM) and non-REM sleep stages, REM sleep latency, wake after sleep onset and arousals] and MRI-derived measures. Then, a principal component analysis (PCA) was used to obtain derived patterns of sleep-wake regulation. Among sleep-promoting regions, higher anterior hypothalamic volumes correlated with greater time in bed (ρ = 0.19, P < 0.05), increased sleep period time (SPT) (ρ = 0.25, P < 0.01), and decreased REM over SPT (ρ = -0.22, P < 0.05). Within wake-promoting structures, higher posterior hypothalamic volume and LC integrity were associated with higher arousals (ρ = 0.32, P < 0.05 and ρ = 0.18, P < 0.05, respectively), and higher basal forebrain volume was associated with less REM over SPT (ρ = -0.25, P < 0.05). Control anatomic regions showed no associations with sleep parameters. The first two principal components of the PCA explain 47.7% of the variance. Anterior hypothalamic volumes clustered with longer, more efficient sleep, whereas LC integrity aligned with increased wakefulness and REM sleep latency. Alzheimer's disease participants showed a shift towards the latter pattern, indicating disrupted sleep-wake regulation. MRI-derived measures of subcortical sleep-wake regions were associated with clinical sleep phenotypes in Alzheimer's disease and ageing. These in vivo findings align with prior post-mortem research, reinforcing the role of subcortical structures in sleep disturbances and highlighting these circuits as potential targets to alleviate sleep symptoms and modify disease progression.

A significant challenge in the study of neuroimmune responses is the identification and separation of resident microglia from infiltrating bone marrow-derived macrophages. Therefore, we investigated whether dual labelling of Cx3cr1 and Ccr2 is sufficient to discriminate retinal microglia from infiltrating macrophages in mice that develop spontaneous autoimmune uveoretinitis-a condition dependent on infiltration of lymphocytes and antigen presenting cells from the circulation into the retina. Mice expressing red fluorescent protein (RFP) under control of the Ccr2 promoter and green fluorescent protein (GFP) under control of the Cx3cr1 promoter (Ccr2[RFP]Cx3cr1[GFP] mice) were crossed with the uveitogenic R161H mouse line. Retinas of R161H[neg] x Ccr2[RFP+/-]Cx3cr1[GFP+/-] F1 mice, including those given an optic nerve crush injury to stimulate retinal MG expansion, and R161H[+/-] x Ccr2[RFP+/-]Cx3cr1[GFP+/-] F1 mice were analyzed for RFP and GFP expressing cells by fundoscopy, flow cytometry, fluorescence microscopy, and for Ccr2 expression by single cell RNA sequencing of retinal CD45[+] cells. Retinas from control and optic nerve crushed R161H[neg] x Ccr2[RFP+/-]Cx3cr1[GFP+/-] F1 mice contained a single population of CD45[+] cells expressing a uniquely high level of GFP but were devoid of RFP[+] cells, while retinas from R161H[+/-] x Ccr2[RFP+/-]Cx3cr1[GFP+/-] F1 mice had GFP[hi] cells and increasing amounts of GFP[neg]RFP[+] and GFP[lo-med]RFP[+] cells as uveoretinitis progressed. Thus, dual labelling of Ccr2 and Cx3cr1 can distinguish retinal microglia from infiltrating immune cells, and as GFP[+], RFP[+], and GFP[+]RFP[+] cells can be easily separated by flow cytometry, our system provides a method for their separation for downstream cellular analysis.