Biology subjects

Rosito, M.

Publications and source records attributed to Rosito, M..

8 recordsLinked to original sources

bioRxiv2026

Effects of aging on multiple object tracking under normal and altered viewing conditions

Multiple object tracking (MOT) is a core function of dynamic visual attention that relies on the ability to simultaneously monitor several moving objects. Although MOT performance is known to decline with age, and to depend on efficient oculomotor strategies, how these processes interact across the adult lifespan and under degraded visual input remains poorly understood. Here, we examined the effects of aging on MOT under normal and gaze-contingent viewing conditions simulating central and peripheral visual field loss. Sixty participants aged 20-80 years completed a MOT task while eye movements were recorded, enabling characterization of performance and oculomotor behavior across five viewing conditions. Behavioral results revealed a continuous decline in tracking performance across adulthood, indicating a graded rather than categorical effect of age. Performance was strongly reduced by visual-field restrictions, with the largest impairments under central vision occlusion. Eye-tracking analyses showed that better performance was associated with greater reliance on centroid-based gaze strategies, consistent with distributed monitoring of target configurations. Critically, older adults relied more on focal, target-based tracking under conditions simulating peripheral vision loss, and less on centroid-based strategies; this shift was associated with poorer performance. In contrast, oculomotor behavior during full-field viewing was largely preserved across age. Together, these findings suggest that aging affects multiple object tracking through combined sensory, attentional, and oculomotor mechanisms. Beyond a reduction in capacity, age-related decline also reflects systematic changes in visual sampling strategies during dynamic tracking.

animal behavior and cognition↗

bioRxiv2025

Vitamin D differentially modulates effector and regulatory T-cell migration across the blood-brain barrier

Multiple sclerosis (MS) is an inflammatory disease of the CNS influenced by a combination of genetic predisposition and environmental factors. Vitamin D (VitD) deficiency is considered a major risk factor for MS. While VitD is associated with immunomodulatory roles, the exact mechanisms by which VitD protects from disease are still largely unknown. CD4 T cells play a key role in MS pathogenesis with autoimmune effector T cells (Teff) infiltrating the CNS across the blood-brain barrier (BBB) and regulatory T cells (Treg) displaying impaired functions. Here we show that treatment of human CD4 T cells with the active form of VitD (1,25-Dihydroxyvitamin D3; 1,25(OH)2D3) decreased cell-surface expression of 4{beta}1- and L{beta}2-integrins on Teff but not Treg and reduced Teff adhesion to their endothelial ligands VCAM-1 and ICAM-1. By employing live cell imaging, we observed that VitD treatment reduced arrest of Teff but not Treg to the BBB as well as ICAM-1 and VCAM-1 under physiological flow in vitro and differentially affected post-arrest behaviour of Teff versus Treg on the BBB under physiological flow. Furthermore, VitD treatment favoured the migration of Treg over Teff across the BBB under static and flow conditions in vitro. In vivo live cell imaging showed that VitD reduced T cell arrest on the inflamed BBB during autoimmune neuroinflammation. Finally, VitD also reduced expression of integrins mediating CNS homing on pathogenic CD4 T cells isolated from the CSF of persons with MS (PwMS). As VitD treatment did not alter barrier properties or adhesion molecule profile of our BBB model we propose a beneficial effect of VitD supplementation in PwMS by reducing CNS trafficking of pro-inflammatory T cells while leaving CNS entry of Treg unaffected.

immunology↗

bioRxiv2025

Cortical Processing for the Vestibular and Visual Input of Egomotion in Macaque Monkeys: Separate Networks with Targeted Convergence

The integration of visual and vestibular inputs during egomotion is fundamental for both postural and navigational control. In the present study, we used functional magnetic resonance imaging (fMRI) in four macaque monkeys to investigate cortical activation in response to galvanic vestibular stimulation (GVS), applied through transmastoid electrodes, and egomotion-compatible (EC) optic flow patterns. Visual and vestibular stimulations activate two largely independent cortical networks: the vestibular network encompasses the insular cortex, superior parietal lobule, frontal lobe, and cingulate cortex, while optic flow primarily activates regions in the superior temporal sulcus, temporo-parietal junction, inferior parietal lobule, and restricted portions of the cingulate and frontal cortices. Despite this segregation, several areas exhibit visuo-vestibular convergence: VPS in the temporo-parietal junction, area 7 in the inferior parietal lobule, VIP and LIP in the intraparietal sulcus, MSTd in the superior temporal sulcus, CSv in the cingulate sulcus, and FEFsem in the frontal cortex. These findings demonstrate that visual and vestibular signals generated by egomotion are processed in extended and distinct cortical networks with several narrow convergence sites, consistent with the idea that multisensory integration during self-motion is achieved through selective convergence rather than general network overlap.

neuroscience↗

bioRxiv2024

Visuo-Vestibular Integration for Self-Motion: Human Cortical Area V6 Prefers Forward and Congruent Stimuli

BACKGROUNDThe integration of visual and vestibular input is crucial for self-motion. Information from both sensory systems merges early in the central nervous system. Among the numerous cortical areas involved in processing this information, some (V6 and VIP) respond specifically to vestibular anteroposterior information. OBJECTIVETo further understand the involvement of these and other areas in self-motion processing when vestibular and visual information are combined with varying congruence and direction parameters. METHODSFifteen subjects underwent an MRI session while receiving visual (optic flow patterns) and galvanic vestibular stimuli mimicking six conditions: (1) visual forward, (2) visual backward, visual forward with (3) congruent or (4) incongruent vestibular information, visual backward with (5) congruent or (6) incongruent vestibular information. RESULTSThe combination of concurrent vestibular stimulation and fully consistant optic flow patterns activated several bilateral cortical areas found predominantly in the insula. Among these vestibular areas and those previously defined in our initial study, the large majority do not show any specifity for the forward/backward direction or for the visuo-vestibular congruency. A notable exception was the parieto-occipital area V6, which showed a marked preference for congruent visuo-vestibular signals and for cues signaling forward motion. CONCLUSIONSBy showing that V6 is more active when visuo-vestibular signals are more ecological (i.e. when both signals specify the most common self-motion direction), our results support the view that this area plays a crucial role in visuo-vestibular integration during self-motion.

neuroscience↗

bioRxiv2022

Reactive microglia and cytokine release entails microtubule remodeling from acentrosomal to centrosomal arrays

Microglia reactivity entails a large-scale remodeling of cellular geometry, but the role of the microtubule cytoskeleton during these changes remains unexplored. Here we show that reactive proinflammatory microglia provide a heretofore unique example of microtubule reorganization from a non-centrosomal array of parallel and stable microtubules to a radial array of more dynamic microtubules. While in the homeostatic state microglia nucleate microtubules at Golgi outposts, proinflammatory signaling induces recruitment of nucleating material nearby the centrosome and inhibition of centrosomal maturation enhances NLRP3 inflammasome activation and secretion of IL-1{beta}. Our results demonstrate that a hallmark of microglia reactivity is a striking remodeling of the microtubule cytoskeleton and suggest that pericentrosomal microtubule nucleation may serve as a distinct marker of microglia activation as well as a novel target to modulate cytokine-mediated inflammatory responses in chronic disease and tissue injury.

cell biology↗

bioRxiv2021

Microglia control glutamatergic synapses in the adult mouse hippocampus

Microglial cells are active players in regulating synaptic development and plasticity in the brain. However, how these cells influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological depletion of microglia, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features accompanied by higher levels of plasticity. In addition, microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. Remarkably, microglial repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in synaptic organization and activity of glutamatergic synapses.

neuroscience↗

bioRxiv2020

Novel fragile X syndrome 2D and 3D brain models based on human isogenic FMRP-KO iPSCs

Fragile X syndrome (FXS) is a neurodevelopmental disorder, characterized by intellectual disability and sensory deficits, caused by epigenetic silencing of the FMR1 gene and subsequent loss of its protein product, fragile X mental retardation protein (FMRP). Delays in synaptic and neuronal development in the cortex have been reported in FXS mouse models, however, the main goal of translating lab research into pharmacological treatments in clinical trials has been so far largely unsuccessful, leaving FXS a still incurable disease. Here, we generated 2D and 3D in vitro human FXS model systems based on isogenic FMR1 knock-out mutant and wild-type human induced pluripotent stem cell (hiPSC) lines. Phenotypical and functional characterization of cortical neurons derived from FMRP-deficient hiPSCs display altered gene expression and impaired differentiation when compared with the healthy counterpart. FXS cortical cultures show increased proliferation of GFAP positive cells, likely astrocytes, increased spontaneous network activity and depolarizing GABAergic transmission. Cortical brain organoid models show increased proliferation of glial cells, and bigger organoid size. Our findings demonstrate that FMRP is required to correctly support neuronal and glial cell proliferation, and to set the correct excitation/inhibition ratio in human brain development.

neuroscience↗

bioRxiv2020

RNA-binding protein network alteration causes aberrant axon branching and growth phenotypes in FUS ALS mutant motoneurons

Mutations in the RNA-binding protein (RBPs) FUS have been genetically associated with the motoneuron disease amyotrophic lateral sclerosis (ALS). Using both human induced pluripotent stem cells and mouse models, we found that FUS-ALS causative mutations affect the activity of two relevant RBPs with important roles in neuronal RNA metabolism: HuD/ELAVL4 and FMRP. Mechanistically, mutant FUS leads to upregulation of HuD protein levels through competition with FMRP for HuD mRNA 3UTR binding. In turn, increased HuD levels overly stabilize the transcript levels of its targets, NRN1 and GAP43. As a consequence, mutant FUS motoneurons show increased axon branching and growth upon injury, which could be rescued by dampening NRN1 levels. Since similar phenotypes have been previously described in SOD1 and TDP-43 mutant models, increased axonal growth and branching might represent broad early events in the pathogenesis of ALS.

neuroscience↗