Biology subjects

Arrigoni, E.

Publications and source records attributed to Arrigoni, E..

12 recordsLinked to original sources

bioRxiv2026

Induction of interhemispheric visual plasticity by paired associative stimulation

Unveiling the plastic mechanisms of the primary visual cortex (V1) is crucial for understanding how visual processing can change and adapt, ultimately informing interventions to promote functional recovery following visual system damage. Paired associative stimulation (PAS) protocols can induce associative plasticity within the human V1. However, previous paradigms used full-field visual stimulation, engaging both hemispheres simultaneously, leaving unclear whether plasticity can be selectively targeted to a single visual pathway and whether it can modulate the non-stimulated hemisphere. Across three experiments in healthy participants, we investigated the neurophysiological, behavioural, and interhemispheric outcomes of a novel lateralized visual PAS protocol (vPAS). Pattern-reversal checkerboards were presented in a single visual hemifield and time-locked to transcranial magnetic stimulation (TMS) pulses delivered over the contralateral V1. Experiment 1 assessed neurophysiological effects by recording hemifield-lateralized visual-evoked potentials (VEPs) and testing three inter-stimulus intervals (ISIs: 75, 100, and 125 ms) between vPAS-paired stimuli. Experiment 2 evaluated perceptual changes in contrast detection, while Experiment 3 examined vPAS hemispheric specificity and aftereffects on interhemispheric visuomotor transfer. Only the 75-ms ISI consistently modulated visual processing in the non-conditioned hemisphere, reducing N75 amplitude and improving contrast detection for visual stimuli presented contralateral to the TMS side. Longer ISIs were not effective. Furthermore, this protocol altered interhemispheric transfer exclusively when the left, but not the right, V1 was targeted during vPAS. In conclusion, lateralized vPAS induces timing-dependent changes beyond the stimulated cortex, suggesting that associative plasticity can engage contralateral visual circuits and modulate visual processing.

neuroscience↗

bioRxiv2025

Molecular Logic of Cell Diversity and Circuit Connectivity in the REM Sleep Hub

The complexity of the brain arises from the diversity of its circuits and the molecular heterogeneity of the cells that compose them. A mechanistic understanding therefore requires mapping cellular identity and connectivity at single-cell resolution. Here we define the cellular taxonomy of the murine sublaterodorsal tegmental nucleus (SLD), a critical hub for REM sleep, using single-nucleus RNA sequencing. We identified all major brain cell classes, with oligodendrocytes as the most abundant, and resolved seventeen transcriptionally distinct neuronal groups defined by neurotransmitters, neuromodulators, and neuropeptides, each with unique molecular signatures. Projection-specific analysis further revealed that glutamatergic subpopulations targeting the ventrolateral periaqueductal gray (vlPAG) and ventral medulla are molecularly distinct, marked by characteristic receptor motifs. Strikingly, we provide the first direct evidence that SLDGLUT neurons innervate the vlPAG. This newly uncovered SLDGLUT[->]vlPAG pathway represents a previously unrecognized circuit node for REM sleep regulation, with the potential to act as a REM-OFF population suppressing it. Together, these findings establish a transcriptionally resolved atlas of the SLD, reveal the molecular logic of its circuit connectivity, and nominate candidate molecular actuators of REM sleep control, opening new avenues for dissecting how brainstem circuits orchestrate REM state and its transitions.

neuroscience↗

bioRxiv2025

Cortical markers of PAS-induced long-term potentiation and depression in the motor system: A TMS-EEG Registered Report

Paired associative stimulation (PAS), a neuromodulation protocol combining transcranial magnetic stimulation (TMS) pulses to the primary motor cortex (M1) with electrical median nerve stimulation, promotes synaptic plasticity (long-term potentiation - LTP, long-term depression - LTD) in the human motor system following Hebbian associative plasticity induction. To date, PAS effects have been mainly investigated at the corticospinal level. In the present Registered Report, we leveraged TMS and electroencephalography (TMS-EEG) co-registration to track the cortical dynamics related to M1-PAS, aiming to characterize the neurophysiological substrates better, grounding the effectiveness of such protocol. In two within-subject sessions, 30 healthy participants underwent the standard M1-PAS protocols inducing LTP (PASLTP) and LTD (PASLTD) while measuring motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) from M1 stimulation before, immediately after, and 30 minutes from the end of the PAS, applied both at supra- (i.e., 110%) and sub- (i.e., 90%) resting motor threshold intensities. Besides replicating MEPs enhancement and inhibition after PASLTP and PASLTD, our results showed that the P30 and N100 M1-TEPs components were significantly modulated immediately following PASLTP and PASLTD administration. These effects were detectable only in suprathreshold conditions, suggesting that M1 subthreshold stimulation could not be optimal for tracking cortical effects of PAS. Furthermore, exploratory analyses showed that P60 amplitude at baseline successfully predicted the magnitude of P30 modulations after PASLTP administration. Our findings provide compelling evidence about the specificity of early TEP components in reflecting changes in M1 reactivity underpinning PAS effects and associative plasticity induction within the motor system. From a broader perspective, our study fosters evidence about using TMS-EEG biomarkers to track complex plastic changes induced in the human brain, exploiting neuromodulatory non-invasive brain stimulation protocols based on associative mechanisms, like PAS. Preregistered Stage 1 protocol: https://osf.io/detjc (date of in-principle acceptance: 15/01/2024) Recommended Stage 2 manuscript: https://rr.peercommunityin.org/articles/rec?id=1031

neuroscience↗

bioRxiv2025

Frontal connectivity dynamics encode contextual information during action preparation

The context in which we perform motor acts shapes our behavior, with movement speed and accuracy modulated by contingent factors, such as the occurrence of cues that trigger or inhibit our actions. This flexibility relies on network interactions encompassing premotor and prefrontal regions, including the supplementary motor area (SMA) and the right inferior frontal gyrus (rIFG). However, the dynamic interplay between these regions during action preparation and execution based on contextual demands remains unclear. Here, we demonstrate that contextual information is encoded in SMA and rIFG interareal connectivity before action. Using Transcranial Magnetic Stimulation (TMS) and electroencephalography (EEG) during Go/No- Go tasks with varying target probabilities, we found that, during the preparatory stages of action, -band rIFG connectivity increased in contexts where motor responses were more frequently withheld. In contrast, SMA exhibited a reversed pattern only near the target onset. Finally, {beta}-band connectivity encoded proactive inhibition processes, increasing when action likelihood was low. Accordingly, during response implementation, both areas exhibited greater {beta}-band connectivity when action was withheld compared to when a motor response was required, further supporting its role in inhibitory control. Our results demonstrate that - and {beta}-band oscillatory network dynamics support context-sensitive adaptations, illustrating how premotor and prefrontal regions synergistically modulate their interactions as they transition from preparation to response. These findings advance understanding of how the brain integrates predictive information to dynamically organize motor and cognitive resources before an action unfolds, revealing that connectivity encodes critical information driving behavior. Significance statementAdaptive behavior relies on the brains ability to anticipate and adjust actions based on contextual cues. Using Transcranial Magnetic Stimulation and electroencephalography (TMS-EEG), we show that the supplementary motor area (SMA) and the right inferior frontal gyrus (IFG) dynamically modulate their functional connectivity based on target predictability during action preparation and initiation. We reveal distinct oscillatory mechanisms by which SMA enhances motor readiness and IFG supports inhibitory control before action execution. These findings provide new insights into how frontal networks integrate probabilistic information to optimize action outputs in predictable contexts, with implications for disorders involving deficits in motor planning and control.

neuroscience↗

bioRxiv2025

Suprachiasmatic Neuromedin-S Neurons Regulate Arousal

Mammalian circadian rhythms, which orchestrate the daily temporal structure of biological processes, including the sleep-wake cycle, are primarily regulated by the circadian clock in the hypothalamic suprachiasmatic nucleus (SCN). The SCN clock is also implicated in providing an arousal signal, particularly during the wake-maintenance zone (WMZ) of our biological day, essential for sustaining normal levels of wakefulness in the presence of mounting sleep pressure. Here we identify a role for SCN Neuromedin-S (SCNNMS) neurons in regulating the level of arousal, especially during the WMZ. We used chemogenetic and optogenetic methods to activate SCNNMS neurons in vivo, which potently drove wakefulness. Fiber photometry confirmed the wake-active profile of SCNNM neurons. Genetically ablating SCNNMS neurons disrupted the sleep-wake cycle, reducing wakefulness during the dark period and abolished the circadian rhythm of body temperature. SCNNMS neurons target the dorsomedial hypothalamic nucleus (DMH), and photostimulation of their terminals within the DMH rapidly produces arousal from sleep. Pre-synaptic inputs to SCNNMS neurons were also identified, including regions known to influence SCN clock regulation. Unexpectedly, we discovered strong input from the preoptic area (POA), which itself receives substantial inhibitory input from the DMH, forming a possible arousal-promoting circuit (SCN->DMH->POA->SCN). Finally, we analyzed the transcriptional profile of SCNNMS neurons via single-nuclei RNA-Seq, revealing three distinct subtypes. Our findings link molecularly-defined SCN neurons to sleep-wake patterns, body temperature rhythms, and arousal control. Significance StatementOur studys findings provide a cellular and neurobiological understanding of how Neuromedin-S (NMS)-containing SCN neurons contribute to regulating circadian rhythms, sleep-wake patterns, body temperature, and arousal control in mammals. This research illuminates the circuit, cellular, and synaptic mechanisms through which SCN neurons regulate daily cycles of wakefulness and sleep, with implications for understanding and potentially manipulating these processes in health and disease.

neuroscience↗

bioRxiv2024

Identifying the Brain Circuits that Regulate Pain-Induced Sleep Disturbances

Pain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours. This relationship is facilitated by the transmission of nociceptive signals through the spino-parabrachial pathways, converging at the wake-active PBelCGRP (parabrachial nucleus expressing Calcitonin Gene-Related Peptide) neurons, known to gate aversive stimuli. However, it has never been tested whether the targeted blocking of this wake pathway can alleviate pain-induced sleep disturbances without increasing sleepiness. Therefore, we next used selective ablations or optogenetic silencing and identified the key role played by the glutamatergic PBelCGRP in pain-induced sleep disturbances. Inactivating the PBelCGRP neurons by genetic deletion or optogenetic silencing prevented these sleep disturbances in both pain models. Furthermore, to understand the wake pathways underlying the pain-induced sleep disturbances, we silenced the PBelCGRP terminals at four key sites in the substantia innominata of the basal forebrain (SI-BF), the central nucleus of Amygdala (CeA), the bed nucleus of stria terminalis (BNST), or the lateral hypothalamus (LH). Silencing of the SI-BF and CeA also significantly reversed pain-induced sleep loss, specifically through the action on the CGRP and NMDA receptors. This was also confirmed by site-specific blockade of these receptors pharmacologically. Our results highlight the significant potential for selectively targeting the wake pathway to effectively treat pain and sleep disturbances, which will minimize risks associated with traditional analgesics. One sentence summaryParabrachial CGRP neurons regulate awakenings to pain.

neuroscience↗

bioRxiv2024

M1 Large-scale Network Dynamics Support Human Motor Resonance and Its Plastic Reshaping

Motor resonance - the activation of the observers motor system when viewing others actions - grounds the intertwined nature of action perception and execution, with profound implications for social cognition and action understanding. Despite extensive research, the neural underpinnings supporting motor resonance emergence and rewriting remain unexplored. In this study, we investigated the role of sensorimotor associative learning in motor resonance neural mechanisms. To this aim, we applied cross-systems paired associative stimulation (PAS) to induce novel visuomotor associations in the human brain. This protocol, which repeatedly pairs transcranial magnetic stimulation (TMS) pulses over the primary motor cortex (M1) with visual stimuli of actions, drives the emergence of an atypical, PAS-conditioned motor resonance response. Using TMS and electroencephalography (EEG) co-registration during action observation, we tracked the M1 functional connectivity profile during this process to map the inter-areal connectivity profiles associated with typical and PAS-induced motor resonance phenomena. Besides confirming, at the corticospinal level, the emergence of newly acquired motor resonance responses at the cost of typical ones after PAS administration, our results reveal dissociable aspects of motor resonance in M1 interregional communication. On the one side, typical motor resonance effects acquired through the lifespan are associated with prominent M1 alpha-band and reduced beta-band connectivity, which might facilitate the corticospinal output while integrating visuomotor information. Conversely, the atypical PAS-induced motor resonance is linked to M1 beta-band cortical connectivity modulations, only partially overlapping with interregional communication patterns related to the typical mirroring responses. This evidence suggests that beta-phase synchronization may be the critical mechanism supporting the formation of motor resonance by coordinating the activity of motor regions during action observation, which also involves alpha-band top-down control of frontal areas. These findings provide new insights into the neural dynamics underlying (typical and newly acquired) motor resonance, highlighting the role of large-scale interregional communication in sensorimotor associative learning within the action observation network.

neuroscience↗

bioRxiv2024

Afferent projections to the Calca/CGRP-expressing parabrachial neurons in mice

The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons which regulate responses to a variety of interoceptive and cutaneous sensory signals. The lateral PB subpopulation expressing the Calca gene which produces the neuropeptide calcitonin gene-related peptide (CGRP) relays signals related to threatening stimuli such as hypercarbia, pain, and nausea, yet the afferents to these neurons are only partially understood. We mapped the afferent projections to the lateral part of the PB in mice using conventional cholera toxin B subunit (CTb) retrograde tracing, and then used conditional rabies virus retrograde tracing to map monosynaptic inputs specifically targeting the PBCalca/CGRP neurons. Using vesicular GABA (vGAT) and glutamate (vGLUT2) transporter reporter mice, we found that lateral PB neurons receive GABAergic afferents from regions such as the lateral part of the central nucleus of the amygdala, lateral dorsal subnucleus of the bed nucleus of the stria terminalis, substantia innominata, and the ventrolateral periaqueductal gray. Additionally, they receive glutamatergic afferents from the infralimbic and insular cortex, paraventricular nucleus, parasubthalamic nucleus, trigeminal complex, medullary reticular nucleus, and nucleus of the solitary tract. Using anterograde tracing and confocal microscopy, we then identified close axonal appositions between these afferents and PBCalca/CGRP neurons. Finally, we used channelrhodopsin-assisted circuit mapping to test whether some of these inputs directly synapse upon the PBCalca/CGRP neurons. These findings provide a comprehensive neuroanatomical framework for understanding the afferent projections regulating the PBCalca/CGRP neurons.

neuroscience↗

bioRxiv2023

A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution

The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kolliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei. In this study, we applied single-nucleus RNA-seq (snRNA-seq) to resolve neuronal subtypes based on their unique transcriptional profiles and then used multiplexed error robust fluorescence in situ hybridization (MERFISH) to map them spatially. We sampled [~]1 million cells across the dPnTg and defined the spatial distribution of over 120 neuronal subtypes. Our analysis identified an unpredicted high transcriptional diversity in this region and pinpointed many neuronal subtypes unique marker genes. We also demonstrated that many neuronal subtypes are transcriptionally similar between humans and mice, enhancing this studys translational value. Finally, we developed a freely accessible, GPU and CPU-powered dashboard (http://harvard.heavy.ai:6273/) that combines interactive visual analytics and hardware-accelerated SQL into a data science framework to allow the scientific community to query and gain insights into the data.

neuroscience↗

bioRxiv2023

Assessing above and belowground recovery from ammonium sulfate addition and wildfire in a lowland heath: mycorrhizal fungi as potential indicators

Atmospheric pollution containing soil-nitrifying ammonium sulphate is affecting semi-natural ecosystems worldwide. Long-term additions of ammonium sulphate on nitrogen (N)-limited habitats such as heathlands increase climate stress affecting recovery from wildfires. Yet although heathland vegetation largely depends on ericoid mycorrhizal fungi (ErM) to access soil N, we lack a detailed understanding of how prolonged exposure to ammonium sulphate may alter ErM community composition and host plants reliance on fungal partners following wildfire and substantial reductions in ammonium sulphate pollution. Effects on ecosystem processes, particularly carbon stores, also remain uncertain. Ammonium sulphate additions occurred bi-weekly for five years after a 2006 wildfire burnt a UK heathland. Ten years after the treatments ceased (2021), we measured vegetation structure, lichen and lichen photobiont composition, soil characteristics, ErM colonisation, ErM diversity in roots and soil, and assessed their potential as recovery indicators. We found heather height and density, and moss groundcover, were greater in N-enriched plots. Lichen community indices showed significant treatment effects without photobiont differences. Soil pH and Mg, and the proportion of putative ErM fungi in soil were significantly lower in treated plots while soil cation exchange capacity was significantly higher. Increases in soil pH were positively correlated to soil ErM abundance. Soil carbon stock measures were variable and negatively related with soil ErM. Our results indicate that atmospheric pollution following fire can have significant lingering effects and mycorrhizal fungi diversity are a novel and effective ecological tool to assess ecosystem recovery on heathlands. IMPLICATIONS FOR PRACTICEO_LIRecovery of heathlands from wildfire and atmospheric pollution may require decadal scales. Conventional restoration assessment tools lack critical understanding of belowground soil and mycorrhizal fungi interactions and nutritional feedback loops with aboveground hosts. C_LIO_LIGiven that ericoid mycorrhizal fungi (ErM) communities are key nutrient regulators of resilient heathlands, we recommend baseline measurements of ErM diversity and abundance in both soil and dominant plant roots be added to the recovery assessment toolkit prior to commencing restoration or management plans. C_LIO_LIWhat defines ErM recovery, and disentangling effects of ammonium sulphate pollution and fire, remain open questions which only long-term field experiments across pollution gradients will address. C_LI

ecology↗

bioRxiv2021

Top-down contribution to motor network reorganization during action preparation

BACKGROUNDIt is unclear whether the Bereitschaftspotential (BP) recorded in humans during action preparation mirrors motor areas activation escalation, or if its early and late phases reflect the engagement of different functional networks. OBJECTIVEHere, we aimed at recording the TMS evoked-potentials (TEP) stimulating the supplementary motor area (SMA) to assess whether and how cortical excitability and functional connectivity of this region change as the BP increases. We hypothesize that, at later stages, the SMA functional network should become more connected to regions relevant for the implementation of the final motor plan. METHODSWe performed TMS-EEG recordings on fourteen healthy subjects during the performance of a visuomotor Go/No-go task, eliciting and recording cortical activity and functional connectivity at -700 ms and -300 ms before the onset of visual stimuli over the SMA. RESULTSWhen approaching stimulus onset, and thus BP peak, the SMA increased its functional connectivity with movement-related structures in the gamma and alpha bands, indicating a regional top-down preparation to implement the motor act. Beta-band connectivity, instead, was maintained constant for the whole BP time-course, being potentially related to sustained attention required by the experimental task. CONCLUSIONThese findings reveal that the BP is not a mere result of increased activation of the SMA, but the functional networks in which this region is involved qualitatively changes over time, becoming more related to the execution of the motor act.

neuroscience↗

bioRxiv2020

Prevalence and phenology of mycorrhizal colonization across populations of Lycopodiella inundata.

Mycorrhizal fungi are critical components of terrestrial habitats and agroecosystems. Recently, Mucoromycotina fine root endophyte (MucFRE) fungi were found to engage in nutritional mutualism with the rare plant Lycopodiella inundata ( marsh clubmoss), one of the earliest vascular plant lineages known to associate with MucFRE. The extent to which this mutualism plays a role in resilient plant populations can only be understood by examining its occurrence rate and phenological patterns. To test for prevalence and seasonality in colonization, we examined 1,297 individual L. inundata roots collected during spring and autumn 2019 from 11 semi-natural heathlands in Britain and the Netherlands. We quantified presence/absence of MucFRE-like hyphae and vesicles and explored possible relationships between temperature and precipitation in the months immediately before sampling. MucFRE-like hyphae were the dominant mycorrhizal fungi observed in all of the examined heathlands. However, we found significant differences in colonization between the two seasons at every site. Overall, 14% of L. inundata roots were colonised in spring (2.4% with vesicles) compared with 86% in autumn (7.6% with vesicles). Colonization levels between populations were also significantly different, and correlated with temperature and precipitation, suggesting some local environments may be more conducive to hyphal growth. These marked seasonal differences in host-plant colonization suggest that results about mycorrhizal status - typically drawn from single time point collections - should be carefully interpreted. Our findings are directly relevant to habitat restoration, species conservation plans, agricultural bio-inoculation nutrient enhancement treatments, microbial diversity and functional studies of host plants and symbionts.

ecology↗