Biology subjects

Scaglione, A.

Publications and source records attributed to Scaglione, A..

11 recordsLinked to original sources

bioRxiv2026

Dopamine neurons drive basal forebrain reward prediction in milliseconds

Phasic reward prediction signals in ventral tegmental area (VTA) dopamine (DA) neurons and basal forebrain (BF) noncholinergic bursting neurons are remarkably similar despite the distinct circuit organizations and functions of the two systems. Whether this similarity reflects independent computation within each system, inheritance from common upstream circuitry, or causal propagation from one system to the other remains unknown. Here we show that reward prediction signals are tightly coordinated across these two systems, with VTA DA activity causally driving BF bursting neurons on a millisecond timescale. Simultaneous recordings from freely moving rats revealed strong coupling between putative DA neurons and BF bursting neurons on individual trials, both in response amplitude and spike timing. DA activity consistently preceded BF bursting neuron activity by approximately 10 ms across well-trained behavior, learning, and even outside overt task events. In DAT-Cre mice, optogenetic activation of VTA DA neurons rapidly recruited BF bursting neurons at latencies matching those observed during natural DA-BF coupling, while activation of their BF terminals produced responses at still shorter latencies. Conversely, inhibition of DA neurons or their BF terminals suppressed both cue-evoked and, notably, ongoing activity in a substantial subset of BF bursting neurons. Fast DA-evoked BF recruitment persisted after D1/D2 receptor blockade, and anatomical tracing identified glutamatergic DA-to-BF synapses, supporting glutamate co-release as a candidate substrate. Together, these findings reveal a previously unrecognized causal link that enables rapid propagation of reward prediction signals between functionally distinct subcortical systems.

neuroscience↗

bioRxiv2026

Meditation Styles Are Highly Discriminable from EEG at the Subject Level With Limited Generalization Across the Population: A Machine-Learning Study

Meditation has been associated with improvements in attention, emotional regulation, and mental well-being, motivating increasing interest in objective methods for assessing meditative states. In this study, we investigate whether EEG-based machine learning can reliably distinguish between multiple meditation styles and mind-wandering states. EEG data were recorded from experienced meditators performing three meditation styles, Shamatha, Vipassana, and Metta, together with an eyes-closed mind-wandering condition. EEG signals were preprocessed to remove artifacts, and features were extracted from frequency, time-frequency, and time domains. Classification was evaluated using both intra-subject and inter-subject strategies with multiple machine learning classifiers. Results demonstrate high intra-subject classification accuracy across meditation-versus-mind-wandering and meditation-style comparisons, indicating strongly discriminative subject-specific neural signatures. In contrast, inter-subject performance decreased substantially, particularly for distinguishing meditation styles, suggesting considerable inter-individual variability in meditation-related EEG patterns. Furthermore, temporal analysis revealed that classification performance increase over time, indicating that the neural distinctions between meditation states become increasingly pronounced over time. Additionally, t-SNE visualization showed clear within-subject clustering but increased overlap across subjects, explaining the reduced inter-subject generalization. Overall, these findings highlight the potential of EEG-based machine learning for personalized assessment and monitoring of meditative states while emphasizing the challenges of developing subject-independent meditation classification systems.

neuroscience↗

bioRxiv2024

Frequency-Dependent Inter-Brain Synchrony is Modulated by Social Interaction in Freely Moving Mice

Social interaction, a pivotal aspect of human and animal behavior, involves a dynamic exchange of information that shapes behavioral responses, emotional states, and cognitive processes. To gain insights into the neural mechanisms underlying these processes, it is necessary to simultaneously investigate the brain activity of socially interacting subjects. Commonly, the simultaneous study of behavior and brain activity during the execution of social tasks is conducted through Hyperscanning in humans which limits the availability of interventions. Here we describe a new experimental platform that combines the development of a new miniaturized optical system, the "MiCe-Scope", to monitor neural activity across the entire cortical mantle with a behavioral paradigm to perform a Hyperscanning study in freely moving mice engaged in social interaction. Our results revealed inter-brain synchrony across different frequency bands widespread over the entire cortical mantle, modulated by social behavior. This finding suggests that synchronization reflects the mutual prediction performed by the entire cortex in mice of interacting dyads. The presence of different synchronization maps in these frequency bands suggests a multiscale nature of interaction, extending the predictive nature of interaction to cortical areas beyond the medial prefrontal cortex. Our work provides an experimental framework to conduct Hyperscanning studies in an animal model that mirrors findings from human studies.

neuroscience↗

bioRxiv2023

Cortical mapping of the sensory response reveals strong brain-state dependence of the late component

Sensory information must be integrated across a distributed brain network for stimulus processing and perception. Recent studies have revealed specific spatiotemporal patterns of cortical activation for the early and late components of sensory-evoked responses, which are associated with stimulus features and perception, respectively. However, our understanding of how the brain state influences the sensory-evoked activation across the mouse cortex remains limited. In this study, we utilized isoflurane to modulate the brain state and conducted wide-field calcium imaging of Thy1-GCaMP6f mice to monitor the distributed activation evoked by multi-whisker stimulation. Our findings reveal that the level of anesthesia strongly shapes the spatiotemporal features and the functional connectivity of the sensory-activated network. As anesthesia levels decrease, we observe increasingly complex responses, accompanied by the emergence of the late component within the sensory-evoked response. The persistence of the late component under anesthesia raises new questions regarding the potential existence of perception during unconscious states.

neuroscience↗

bioRxiv2021

Large-scale all-optical dissection of motor cortex connectivity reveals a segregated functional organization of mouse forelimb representations

In rodent motor cortex, the rostral forelimb area (RFA) and the caudal forelimb area (CFA) are major actors in orchestrating the control of forelimb complex movements. However, their intrinsic connections and reciprocal functional organization are still unclear, limiting our understanding of how the brain coordinates and executes voluntary movements. Here we causally probed cortical connectivity and activation patterns triggered by transcranial optogenetic stimulation of ethologically relevant complex movements exploiting a novel large-scale all-optical method in awake mice. Results show specific activation features for each movement class, providing evidence for a segregated functional organization of CFA and RFA. Importantly, we identified a second discrete lateral grasping representation area, namely lateral forelimb area (LFA), with unique connectivity and activation patterns. Therefore, we propose the LFA as a distinct motor representation in the forelimb somatotopic motor map.

neuroscience↗

bioRxiv2021

Combination of a Sindbis-SARS-CoV-2 spike vaccine and αOX40 antibody elicits protective immunity against SARS-CoV-2 induced disease and potentiates long-term SARS-CoV-2-specific humoral and T-cell immunity

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the worlds population at record speeds. However, there is still demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the SARS-CoV-2 spike protein (SV.Spike), combined with the OX40 immunostimulatory antibody (OX40) as a novel, highly effective vaccine approach. We show that SV.Spike plus OX40 elicits long-lasting neutralizing antibodies and a vigorous T-cell response in mice. Protein binding, immunohistochemical and cellular infection assays all show that vaccinated mice sera inhibits spike functions. Immunophenotyping, RNA Seq transcriptome profiles and metabolic analysis indicate a reprogramming of T-cells in vaccinated mice. Activated T-cells were found to mobilize to lung tissue. Most importantly, SV.Spike plus OX40 provided robust immune protection against infection with authentic coronavirus in transgenic mice expressing the human ACE2 receptor (hACE2-Tg). Finally, our immunization strategy induced strong effector memory response, potentiating protective immunity against re-exposure to SARS-CoV-2 spike protein. Our results show the potential of a new Sindbis virus-based vaccine platform to counteract waning immune response that can be used as a new candidate to combat SARS-CoV-2. Given the strong T-cell responses elicited, our vaccine is likely to be effective against variants that are proving challenging, as well as, serve as a platform to develop a broader spectrum pancoronavirus vaccine. Similarly, the vaccine approach is likely to be applicable to other pathogens.

immunology↗

bioRxiv2020

Synergic effect of optogenetic stimulation and motor training boosts recovery of motor functionality after stroke supported by segregation of motor representation

BackgroundAn ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the mechanisms underneath the reshaping of cortical functionality are widely unknown. ObjectiveWe investigated the spatio-temporal features of motor-evoked cortical activity associated with generalized recovery after stroke, and its dependence on the type of rehabilitative treatment. MethodsWe designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. Specifically, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin-2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (i.e. individually administered optogenetic stimulation or motor training). ResultsWe found that only the combined therapy promotes generalized recovery of forelimb function and the rescue of spatio-temporal features of motor-evoked activity. Generalized recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. ConclusionsOur findings demonstrate that though behavioral recovery is not necessarily associated with the restoration of pre-stroke motor-evoked activity, the reestablishment of pre-stroke activation transients was a distinguishing feature of the most efficient therapeutic approach, the combined therapy.

neuroscience↗

bioRxiv2020

A distributed neocortical action map associated with reach-to-grasp

Reach-to-Grasp (RtG) is known to be dependent upon neocortical circuits and extensive research has provided insights into how selected neocortical areas contribute to control dexterous movements. Surprisingly, little infor-mation is available on the global neocortical computations underlying RtG in the mouse. Here, we characterized, employing fluorescence wide-field cal-cium imaging, the neocortex-wide dynamics from mice engaging in a RtG task. We demonstrate that, beyond canonical motor regions, several areas, such as the visual and the retrosplenial cortices, also increase their activ-ity levels during successful RtGs. Intriguingly, homologous regions across the ipsilateral hemisphere are also involved. Functional connectivity among areas increases transiently from rest to planning, and decreases during move-ment. Two anti-correlated neocortical networks emerged during movement. At variance, neural activity levels scale linearly with kinematics measures of successful RtGs in secondary motor areas. Our findings establish the coex-istence of distributed and localized neocortical dynamics for efficient control of complex movements. SIGNIFICANCE STATEMENTIn mammals, including humans, the cerebral cortex is known to be critical for the correct execution of dexterous movements. Despite the importance of the mouse for elucidating the neural circuitry for motor control, its neocortex-wide dynamics during RtG are largely unexplored. We used in-vivo fluores-cence microscopy to characterize the neural activity across the neocortex as mice performed a reach-to-grasp task. We show that for such complex movements, a large network of neocortical areas gets involved, while movement kinematics correlates with neural activity in secondary motor areas. These findings indicate the coexistence, at the mesoscale level, of distributed and localized neocortical dynamics for the execution of fine movements. This study offers a novel view on the neocortical correlates of motor control, with potential implications for neural repair.

neuroscience↗

bioRxiv2019

Rehabilitation promotes the recovery of structural and functional features of healthy neuronal networks after stroke

Rehabilitation is the most effective treatment for promoting the recovery of motor deficits after stroke. One of the most challenging experimental goals is to unambiguously link brain rewiring to motor recovery prompted by rehabilitative therapy. Here, we investigated which aspects of cortical remodeling are induced by rehabilitation by combining optical imaging and manipulation tools in a mouse model of stroke. We revealed that the stabilization of peri-infarct synaptic contacts fostered by rehabilitation goes along with increased vascular density induced by angiogenesis. Furthermore, we showed the progressive formation of a new motor representation in the peri-infarct area where temporal and spatial features of cortical activation recovered towards pre-stroke condition. In the same animals we observed the reinforcement of inter-hemispheric connectivity after rehabilitation. The present work provides the first evidences that rehabilitation promotes the combined recovery of structural and functional features distinctive of healthy neuronal networks.

neuroscience↗

bioRxiv2018

PADI2-mediated citrullination is required for efficient oligodendrocyte differentiation and myelination

Citrullination, the deimination of arginine residues into citrulline, has been implicated in the aetiology of several diseases. In multiple sclerosis (MS), citrullination is thought to be a major driver of pathology, through hypercitrullination and destabilization of myelin. As such, inhibition of citrullination has been suggested as a therapeutic strategy for MS. Here, in contrast, we show citrullination by peptidylarginine deiminase 2 (PADI2) is required for normal oligodendrocyte differentiation, myelination and motor function. We identify several targets for PADI2, including myelin-related proteins and chromatin-associated proteins, implicating PADI2 in epigenetic regulation. Accordingly, we observe that PADI2 inhibition and its knockdown affect chromatin accessibility and prevent the upregulation of oligodendrocyte differentiation genes. Moreover, mice lacking PADI2, display motor dysfunction and decreased number of myelinated axons in the corpus callosum. We conclude that citrullination is required for oligodendrocyte lineage progression and myelination and suggest its targeted activation in the oligodendrocyte lineage might be beneficial in the context of remyelination.

neuroscience↗

bioRxiv2018

Wide-field imaging of cortical neuronal activity with red-shifted functional indicators during motor task execution

Intracellular concentration of free calcium ions in neuronal populations can be longitudinally evaluated by using fluorescent protein indicators, called genetically encoded calcium indicators (GECIs). GECIs with long emission wavelengths are particularly attractive for deep tissue microscopy in vivo, and have the additional advantage of avoiding spectral overlap with commonly used neuronal actuators like Channelrhodopsin.\n\nHere we investigated the performances of selected red-shifted GECIs through an ex vivo characterization and in vivo imaging of cortical mouse activity during motor task execution. Cortical neurons were infected with adeno-associated virus (AAV) expressing one of the red GECI variants (jRCaMP1a, jRCaMP1b, jRGECO1a, jRGECO1b). First we characterized the transfection in terms of extension and intensity using wide-field fluorescence microscopy. Next, we used RCaMP1a to analyse the cortical neuronal activity during motor behaviour. To that end, wide-field fluorescent microscopy and a robotic device for motor control were combined for simultaneous recording of cortical neuronal-activity, force applied and forelimb position during task execution.\n\nOur results show that jRCaMP1a has sufficient sensitivity to monitor in vivo neuronal activity over multiple functional areas, and can be successfully used to perform longitudinal imaging in awake mice.

neuroscience↗