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Cell Reports Jun 2024In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light...
In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light treatment, the circuit mechanisms underlying the effects of light on itch-related behaviors remain poorly understood. In this study, we demonstrate that bright light treatment reduces itch-related behaviors in mice through a visual circuit related to the lateral parabrachial nucleus (LPBN). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which subsequently inhibit CaMKIIα neurons in the LPBN. Activation of both the vLGN/IGL-projecting RGCs and the vLGN/IGL-to-LPBN projections is sufficient to reduce itch-related behaviors induced by various pruritogens. Importantly, we demonstrate that the antipruritic effects of bright light treatment rely on the activation of the retina-vLGN/IGL-LPBN pathway. Collectively, our findings elucidate a visual circuit related to the LPBN that underlies the antipruritic effects of bright light treatment.
PubMed: 38865246
DOI: 10.1016/j.celrep.2024.114356 -
Nature Communications Jun 2024A brain-computer interface (BCI) enables users to control devices with their minds. Despite advancements, non-invasive BCIs still exhibit high error rates, prompting...
A brain-computer interface (BCI) enables users to control devices with their minds. Despite advancements, non-invasive BCIs still exhibit high error rates, prompting investigation into the potential reduction through concurrent targeted neuromodulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive neuromodulation technology with high spatiotemporal precision. This study examines whether tFUS neuromodulation can improve BCI outcomes, and explores the underlying mechanism of action using high-density electroencephalography (EEG) source imaging (ESI). As a result, V5-targeted tFUS significantly reduced the error in a BCI speller task. Source analyses revealed a significantly increase in theta and alpha activities in the tFUS condition at both V5 and downstream in the dorsal visual processing pathway. Correlation analysis indicated that the connection within the dorsal processing pathway was preserved during tFUS stimulation, while the ventral connection was weakened. These findings suggest that V5-targeted tFUS enhances feature-based attention to visual motion.
Topics: Humans; Brain-Computer Interfaces; Male; Electroencephalography; Attention; Adult; Female; Young Adult; Visual Cortex; Motion Perception; Photic Stimulation
PubMed: 38862476
DOI: 10.1038/s41467-024-48576-8 -
Journal of the American Heart... Jun 2024Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and...
BACKGROUND
Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level.
METHODS AND RESULTS
Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with 8 CVD risk factors. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. Replication was carried out in 1999 RS (Rotterdam Study) participants. Pathway enrichment analyses were conducted and target genes were predicted for miRNAs associated with ≥5 risk factors in the FHS. In the FHS, 6 miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, and miR-193a-5p) were associated with ≥5 risk factors. This miRNA signature was enriched for pathways associated with CVD and several genes annotated to these pathways were predicted targets of the identified miRNAs. Furthermore, miR-193b-3p, miR-194-5p, and miR-193a-5p were each associated with ≥2 risk factors in the RS. Prospective analysis revealed 8 miRNAs associated with all-cause mortality in the FHS.
CONCLUSIONS
These findings highlight associations between miRNAs and CVD risk factors that may provide valuable insights into the underlying pathogenesis of CVD.
Topics: Humans; Male; Cardiovascular Diseases; Female; Middle Aged; Aged; MicroRNAs; Heart Disease Risk Factors; Prospective Studies; Cross-Sectional Studies; Risk Assessment; Circulating MicroRNA; Risk Factors; Biomarkers; Age Factors
PubMed: 38860398
DOI: 10.1161/JAHA.123.033674 -
BMC Biology Jun 2024Inherited retinal dystrophies (IRDs) are a group of debilitating visual disorders characterized by the progressive degeneration of photoreceptors, which ultimately lead...
BACKGROUND
Inherited retinal dystrophies (IRDs) are a group of debilitating visual disorders characterized by the progressive degeneration of photoreceptors, which ultimately lead to blindness. Among the causes of this condition, mutations in the PCYT1A gene, which encodes the rate-limiting enzyme responsible for phosphatidylcholine (PC) de novo synthesis via the Kennedy pathway, have been identified. However, the precise mechanisms underlying the association between PCYT1A mutations and IRDs remain unclear. To address this knowledge gap, we focused on elucidating the functions of PCYT1A in the retina.
RESULTS
We found that PCYT1A is highly expressed in Müller glial (MG) cells in the inner nuclear layer (INL) of the retina. Subsequently, we generated a retina-specific knockout mouse model in which the Pcyt1a gene was targeted (Pcyt1a-RKO or RKO mice) to investigate the molecular mechanisms underlying IRDs caused by PCYT1A mutations. Our findings revealed that the deletion of Pcyt1a resulted in retinal degenerative phenotypes, including reduced scotopic electroretinogram (ERG) responses and progressive degeneration of photoreceptor cells, accompanied by loss of cells in the INL. Furthermore, through proteomic and bioinformatic analyses, we identified dysregulated retinal fatty acid metabolism and activation of the ferroptosis signalling pathway in RKO mice. Importantly, we found that PCYT1A deficiency did not lead to an overall reduction in PC synthesis within the retina. Instead, this deficiency appeared to disrupt free fatty acid metabolism and ultimately trigger ferroptosis.
CONCLUSIONS
This study reveals a novel mechanism by which mutations in PCYT1A contribute to the development of IRDs, shedding light on the interplay between fatty acid metabolism and retinal degenerative diseases, and provides new insights into the treatment of IRDs.
Topics: Animals; Mice; Choline-Phosphate Cytidylyltransferase; Fatty Acids; Ferroptosis; Mice, Knockout; Retina; Retinal Dystrophies
PubMed: 38858683
DOI: 10.1186/s12915-024-01932-y -
PLoS Biology Jun 2024Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include...
Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice.
Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments-a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD.
PubMed: 38857283
DOI: 10.1371/journal.pbio.3002668 -
Journal of Physiological Investigation May 2024Diabetic retinopathy (DR) is a secondary complication of diabetes that can lead to visual impairment and blindness. The retinal pigment epithelium (RPE) is a monolayer...
Diabetic retinopathy (DR) is a secondary complication of diabetes that can lead to visual impairment and blindness. The retinal pigment epithelium (RPE) is a monolayer of pigment cells that forms the blood-retinal barrier (BRB) via tight junction (TJ) proteins and plays a crucial role in the physiological function of the retina. Hyperglycemia induces RPE death and BRB breakdown, which accelerates the process of DR. Curcumin, an active extract of Curcuma longa , has anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective properties. However, the effect of Curcumin on the BRB under high glucose conditions remains unknown. This study aimed to investigate the protective effects of Curcumin on RPE physiology in vitro and in vivo . Curcumin significantly alleviated cell viability inhibition under high glucose conditions. Moreover, high glucose reduced extracellular signal-regulated kinase and Akt pathways activation to diminish RPE cell growth but reversed by Curcumin treatment. Curcumin protected not only TJ integrity but also retinoid regeneration through TJ proteins and isomerase modulation in diabetic retina. Furthermore, Curcumin decreased the expression of angiogenic factor to inhibit retinal neovascularization. Finally, Curcumin treatment markedly reduced apoptosis during hyperglycemia. In conclusion, Curcumin can alleviate the progression of DR by promoting RPE survival, TJ integrity, retinoid isomerase activity, RPE senescence inhibition, and neovascularization. Therefore, Curcumin exhibits high potential for use as a therapeutic agent for early DR.
Topics: Curcumin; Diabetic Retinopathy; Retinal Pigment Epithelium; Humans; Cellular Senescence; Tight Junctions; Animals; Male; Apoptosis; Cell Survival; Blood-Retinal Barrier; Mice, Inbred C57BL; Mice
PubMed: 38857204
DOI: 10.4103/ejpi.EJPI-D-23-00035 -
Frontiers in Neuroscience 2024Aesthetic emotions are a class of emotions aroused by evaluating aesthetically appealing objects or events. While evolutionary aesthetics suggests the adaptive roles of...
INTRODUCTION
Aesthetic emotions are a class of emotions aroused by evaluating aesthetically appealing objects or events. While evolutionary aesthetics suggests the adaptive roles of these emotions, empirical assessments are lacking. Previous neuroscientific studies have demonstrated that visual stimuli carrying evolutionarily important information induce neural responses even when presented non-consciously. To examine the evolutionary importance of aesthetic emotions, we conducted a neuroscientific study using magnetoencephalography (MEG) to measure induced neural responses to non-consciously presented portrait paintings categorised as biological and non-biological and examined associations between the induced responses and aesthetic ratings.
METHODS
MEG and pre-rating data were collected from 23 participants. The pre-rating included visual analogue scales for , , , and scores, in addition to ',' which was used for subcategorising stimuli into biological and non-biological. The stimuli were presented non-consciously using a continuous flash suppression paradigm or consciously using binocular presentation without flashing masks, while dichotomic behavioural responses were obtained (beauty or non-beauty). Time-frequency decomposed MEG data were used for correlation analysis with pre-rating scores for each category.
RESULTS
Behavioural data revealed that saliency scores of non-consciously presented stimuli influenced dichotomic responses (beauty or non-beauty). MEG data showed that non-consciously presented portrait paintings induced spatiotemporally distributed low-frequency brain activities associated with aesthetic ratings, which were distinct between the biological and non-biological categories and conscious and non-conscious conditions.
CONCLUSION
Aesthetic emotion holds evolutionary significance for humans. Neural pathways are sensitive to visual images that arouse aesthetic emotion in distinct ways for biological and non-biological categories, which are further influenced by consciousness. These differences likely reflect the diversity in mechanisms of aesthetic processing, such as processing fluency, active elaboration, and predictive processing. The aesthetic processing of non-conscious stimuli appears to be characterised by fluency-driven affective processing, while top-down regulatory processes are suppressed. This study provides the first empirical evidence supporting the evolutionary significance of aesthetic processing.
PubMed: 38855441
DOI: 10.3389/fnins.2024.1339479 -
BioRxiv : the Preprint Server For... May 2024Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied...
Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. Recent work suggests a much greater degree of commonality across areas, with distributed and modular networks present in both sensory and non-sensory areas during early development. However, it is currently unknown whether this initially common modular structure undergoes an equally common developmental trajectory, or whether such a modular functional organization persists in some areas-such as primary visual cortex-but not others. Here we examine the development of network organization across diverse cortical regions in ferrets of both sexes using widefield calcium imaging of spontaneous activity. We find that all regions examined, including both primary sensory cortices (visual, auditory, and somatosensory-V1, A1, and S1, respectively) and higher order association areas (prefrontal and posterior parietal cortices) exhibit a largely similar pattern of changes over an approximately 3 week developmental period spanning eye opening and the transition to predominantly externally-driven sensory activity. We find that both a modular functional organization and millimeter-scale correlated networks remain present across all cortical areas examined. These networks weakened over development in most cortical areas, but strengthened in V1. Overall, the conserved maintenance of modular organization across different cortical areas suggests a common pathway of network refinement, and suggests that a modular organization-known to encode functional representations in visual areas-may be similarly engaged in highly diverse brain areas.
PubMed: 38853883
DOI: 10.1101/2024.05.28.595371 -
BioRxiv : the Preprint Server For... Jun 2024Neocortical circuits use synaptic and intrinsic forms of homeostatic plasticity to stabilize key features of network activity, but whether these different homeostatic...
Neocortical circuits use synaptic and intrinsic forms of homeostatic plasticity to stabilize key features of network activity, but whether these different homeostatic mechanisms act redundantly, or can be independently recruited to stabilize different network features, is unknown. Here we used pharmacological and genetic perturbations both and to determine whether synaptic scaling and intrinsic homeostatic plasticity (IHP) are arranged and recruited in a hierarchical or modular manner within L2/3 pyramidal neurons in rodent V1. Surprisingly, although the expression of synaptic scaling and IHP was dependent on overlapping trafficking pathways, they could be independently recruited by manipulating spiking activity or NMDAR signaling, respectively. Further, we found that changes in visual experience that affect NMDAR activation but not mean firing selectively trigger IHP, without recruiting synaptic scaling. These findings support a modular model in which synaptic and intrinsic homeostatic plasticity respond to and stabilize distinct aspects of network activity.
PubMed: 38853882
DOI: 10.1101/2024.06.01.596982 -
Brain Research Bulletin Aug 2024An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked...
An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked disengagement deficits with superior parietal damage, regardless of hemisphere or presence of spatial neglect. Subsequent studies supported the involvement of more ventral parietal regions, especially in the right hemisphere, and linked spatial neglect to deficient disengagement from ipsilateral cues. However, previous lesion studies faced serious limitations, such as small sample sizes and the lack of brain-injured controls without neglect. Additionally, some studies employed symbolic cues or used long cue-target intervals, which may fail to reveal impaired disengagement. We here used a machine-learning approach to conduct lesion-symptom mapping (LSM) on 89 patients with focal cerebral lesions to the left (LH) or right (RH) cerebral hemisphere. A group of 54 healthy participants served as controls. The paradigm used to uncover disengagement deficits employed non-predictive cues presented in the visual periphery and at short cue-target intervals, targeting exogenous attention. The main factors of interest were group (healthy participants, LH, RH), target position (left, right hemifield) and cue validity (valid, invalid). LSM-analyses were performed on two indices: the validity effect, computed as the absolute difference between reaction times (RTs) following invalid compared to valid cues, and the disengagement deficit, determined by the difference between contralesional and ipsilesional validity effects. While LH patients showed general slowing of RTs to contralesional targets, only RH patients exhibited a disengagement deficit from ipsilesional cues. LSM associated the validity effect with a right lateral frontal cluster, which additionally affected subcortical white matter of the right arcuate fasciculus, the corticothalamic pathway, and the superior longitudinal fasciculus. In contrast, the disengagement deficit was related to damage involving the right temporoparietal junction. Thus, our results support the crucial role of right inferior parietal and posterior temporal regions for attentional disengagement, but also emphasize the importance of lateral frontal regions, for the reorienting of attention.
Topics: Humans; Male; Female; Middle Aged; Parietal Lobe; Attention; Aged; Functional Laterality; Adult; Reaction Time; Frontal Lobe; Perceptual Disorders; Cues; Space Perception; Brain Injuries
PubMed: 38852652
DOI: 10.1016/j.brainresbull.2024.111003