Biology subjects

Olcese, U.

Publications and source records attributed to Olcese, U..

17 recordsLinked to original sources

bioRxiv2026

Neuroline: an integrated modular pipeline for FAIR multimodal neurophysiology data processing

The adoption of FAIR principles for code and data sharing in systems neuroscience is hindered by the size and diversity of datasets, the multitude of data formats and the complexity of analysis workflows. These challenges have led to the development of various data standards and modality-specific processing and analysis tools. However, it remains difficult to integrate the diverse processed data streams originating from state-of-the-art neurophysiology experiments into a common format, which is crucial for cross-modal analyses and open, FAIR sharing of data. To address this, we developed Neuroline, a Python package for processing neurophysiology data (electrophysiology, optical imaging, and behaviour) that combines multimodal integration, modularity, and standardised output within a single pipeline. It leverages established packages and consolidates the resulting processed data into the standardised Neurodata Without Borders (NWB) format. Neuroline provides a unified interface while preserving flexibility and extensibility. Here we describe the implementation and challenges of a pipeline capable of integrating different types of neuroscientific data and packages. Finally, we address how Neuroline contributes to the sustainability and accessibility of neuroscience data and software.

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bioRxiv2026

Behavioral arousal organizes visual cortical population micro-states across the sleep-wake cycle

Brain states are conventionally defined as discrete categories, such as wakefulness, NREM sleep and REM sleep. Yet, whether these labels fully capture the organization of cortical population dynamics remains unclear. Using large-field-of-view two-photon calcium imaging of layer II/III pyramidal neurons in mouse primary visual cortex (V1), we show that population activity organizes into recurring micro-states that span conventional sleep-wake boundaries. A Hidden Markov Model fitted independently of behavioral state labels identified temporally stable micro-states with structured transition pathways. Micro-state organization was more strongly aligned with a continuous behavioral arousal axis, indexed by pupil diameter and orofacial motion, than with discrete NREM-wake categories, a relationship confirmed by mediation analysis. At the circuit level, two spatially intermingled but functionally opposing neuronal ensembles tracked this arousal axis in opposite directions. These findings establish behavioral arousal, rather than discrete wake-sleep state, as the primary organizing dimension of V1 population dynamics.

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bioRxiv2026

Theta phase-locked memory reactivation during REM sleep reduces memories emotional tone

REM sleep appears to be involved in emotional memory processing, yet the nature and neural underpinnings of this involvement remain largely unclear. Recent findings suggest REM-related theta activity may play a central role. To test this, we developed an automated protocol to target non-arousing acoustic memory cues to specific phases of REM sleep theta oscillations. During sleep, participants who had undergone a fear conditioning procedure combined with a memory recollection and emotional evaluation task, were re-exposed to conditioned stimuli, timed to either the upswing or downswing of theta waves. Both up- and down-targeted memory cues significantly enhanced the theta dynamic. Moreover, theta phase-locked memory reactivation significantly reduced the emotional tone of conditioned memories compared to sham reactivation (no acoustic memory cue), without affecting recognition performance or dream qualities. This constitutes the first evidence that REM sleep theta oscillations are causally involved in emotional memory processing, specifically in attenuating memories emotional charge. These findings have important implications for understanding emotional memory consolidation and may lead to therapeutic applications in disorders featuring maladaptive emotional memories.

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bioRxiv2026

Sound-evoked orofacial motion only affects a fraction of visually responsive V1 neurons in a multisensory detection task with delayed reward delivery

Auditory stimuli have been known to elicit neural responses in visual cortical areas, but such responses are partly associated with sound-evoked orofacial movements. However, it remains unclear to what extent neural correlates of movement can be dissociated from non-motor correlates. Here we developed a paradigm with a forced delayed-response mechanism by means of a moving reward apparatus in order to test whether this results in low amounts of movement-related neural activity shortly after stimulus onset. Animals performed a multisensory detection task, while we recorded neural activity from V1 and measured orofacial motion. During the delay, when only the stimulus was present, orofacial motion was relatively low. Reward-related motion increased after the delay, with a concomitant increase in motor-related spiking activity. Visual stimulation did neither elicit considerable motion nor corresponding neural responses in the delay period. Conversely, salient auditory stimuli led to modest, but increased orofacial motion and related neuronal activity during the delay. We identified a subpopulation of visually responsive V1 neurons that did not show correlations with orofacial movement, with only the stimulus being represented. These results present a forced delayed-response window as a method to help disentangle motor-related activity from visual (but not auditory) processing and show that motor-related activity only affects a fraction of visually selective neurons.

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bioRxiv2026

Posterior but not frontal neural signatures of subjective visibility in report-independent EEG decoding

A central question in consciousness research is whether perceptual awareness arises predominantly from activity in posterior sensory regions or from later frontal processes associated with access and report. Empirical tests of these alternatives are challenging because most paradigms rely on explicit perceptual reports, introducing motor and decisional confounds. Here, we used an electroencephalography design combining two independent tasks to isolate neural signatures of subjective visibility while minimizing report-related activity. Participants viewed lateralized gratings in a backward-masking task and rated their subjective visibility, while in a separate no-report task they viewed unmasked gratings without reporting. Classifiers were trained on stimulus location in the no-report task and tested on masked trials sorted by subjective visibility in the masking task. This cross-decoding approach isolates stimulus-specific neural representations that generalize across tasks and are therefore independent of reporting and decision processes. Decoding revealed a reliable difference between subjectively visible and invisible stimuli in an early time window from 130 to 170 milliseconds, driven by posterior sensors over occipital, temporal, and parietal regions. No corresponding effects were observed over frontal sensors. These results indicate that subjective awareness is associated with early, posterior neural representations, whereas frontal activity observed in report-based paradigms likely reflects post-perceptual processing rather than awareness per se.

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bioRxiv2026

Baseline activity of V1 interneurons connects pupil-linked arousal to engaged behavioral state

AO_SCPLOWBSTRACTC_SCPLOWHumans and rodents alternate between discrete, persistent behavioral states during perceptual decision-making. For example, trials can be clustered into states of engaged, disengaged, and biased decision-making strategies. In mice, the probability of being in an engaged state exhibits an inverted-U relationship with baseline pupil-linked arousal, consistent with the Yerkes-Dodson Law. We replicated this relationship in mice (N=11; audio-visual change detection task) and showed that it generalizes to humans (N=69; auditory detection task). We then examined its neural basis, using simultaneous pupillometry and electrophysiological recordings in mouse V1. A nonlinear mediation model revealed that baseline activity of putative fast-spiking interneurons, but not putative pyramidal neurons, made a significant statistical contribution to the inverted-U shaped relationship between pupil-linked arousal and engaged-state probability. These findings are consistent with the idea that arousal may shape behavioral states by modulating baseline inhibitory activity within a primary sensory region.

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bioRxiv2025

Functional connectivity drifts during sleep as a marker of fluctuations in the level of consciousness

During the wake-sleep cycle, consciousness waxes and wanes, and this is thought to be reflected in varying levels of integration between brain areas. Recent studies challenged the notion that consciousness is homogeneously present or absent in a brain state, as exemplified by conscious reports found in otherwise unconscious Non-REM sleep. We tested if functional connectivity between neurons varies within brain states in a way compatible with a fluctuating level of consciousness. We examined directed functional connectivity between neurons across the wake-sleep cycle in rats, at a scale of a few seconds. We analyzed patterns of functional connectivity to determine if Non-REM sleep contains epochs in which inter-areal integration is comparable to that observed in wakefulness and REM sleep, and vice versa. This study will potentially reveal if circuit-level connectivity patterns are observed during sleep stages, in line with the presence of an alternation between levels of consciousness not only between but also within brain states.

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bioRxiv2025

A polymeric, PDMS-based large-scale skull replacement suitable for optical and mechanical access for long-term neuronal imaging, electrophysiology, and optogenetics

Many techniques to record and manipulate neuronal activity across large portions of the vertebrate brain, such as widefield and two-photon calcium imaging, electrophysiology, and optogenetics, are now available. However, few effective approaches enable both optical and mechanical access to the brain. In this work, we offer an in-depth guide for synthesizing, implanting, and using polydimethylsiloxane (PDMS) windows as skull replacements for chronic optical neuronal imaging. Furthermore, we provide instructions to perform viral injections and multi-site silicon probe implantation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/648966v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@1900a2dorg.highwire.dtl.DTLVardef@18c436corg.highwire.dtl.DTLVardef@19e6a4corg.highwire.dtl.DTLVardef@154c228_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG

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bioRxiv2025

Audiovisual processing is selectively impaired in the primary visual cortex but not in the posterior parietal cortex of a mouse model of Fragile X syndrome

Sensory processing disruptions are a common feature in various forms of autism spectrum disorders (ASD), yet the circuit-level mechanisms underlying these deficits remain poorly understood. Here, we examined differences in audiovisual processing between wild-type and Fmr1-knockout (KO) mice, a model of Fragile X syndrome, which itself represents the most common hereditary cause of autism. We performed multi-area Neuropixels probe recordings in the primary visual cortex (V1) and posterior parietal cortex (PPC) of head-fixed, anesthetized mice being shown visual and auditory stimuli. Previous studies generally reported sensory hypersensitivity in Fragile X mice. In contrast, we observed reduced visual and auditory responses in V1 (but not PPC) of Fragile X compared to wild-type mice. Auditory stimuli reduced the amplitude of visual responses in both V1 and PPC across the two lines, but a dependency on the relative timing of the two sensory modalities was only observed in wild-type mice. Our results provide evidence for a region-specific sensory-processing phenotype of ASD, something that needs to be taken into account when evaluating the efficacy of pharmacological and behavioral strategies to address ASD symptoms.

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bioRxiv2024

Circuit-Level Dynamics of Slow Wave Activity and Propagation During the Awakening Process

Slow-wave activity (SWA) is a hallmark of the loss of consciousness in non-REM sleep and anesthesia. The mechanistic underpinnings of SWA, and its evolution when transitioning towards the conscious brain state is poorly understood. We address this topic by recording multi-area and laminar activity in posterior parietal (PPC) and primary visual (V1) cortices of mice spontaneously awakening from isoflurane anesthesia. Spectral power is stronger in PPC (especially in superficial layers) during deep unconsciousness, but stronger in V1 when awakening. Rostro-caudal (feedback-like) propagation of SWA also shows state-dependent modulation, particularly in layer 5. The excitability of layer 2/3 neurons, hindered at high isoflurane, recovers during awakening, when V1 and the feedforward pathway reacquire a strong role. Detailing the hierarchical and laminar properties of spontaneous traveling oscillations, we provide evidence that SWA is a multiscale phenomenon. Explicating the functional role of these processes is critical to understand the neuronal mechanisms of consciousness.

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bioRxiv2024

Increased perceptual reliability reduces membrane potential variability in cortical neurons

Uncertainty is omnipresent. While humans and other animals take uncertainty into account during decision making, it remains unclear how it is represented in cortex. To investigate the effect of stimulus reliability on uncertainty representation in cortical neurons, we analyzed single unit activity data recorded in mouse PPC, while animals performed a multisensory change detection task. We further used simulation-based inference (SBI) to infer membrane potential statistics underlying the spiking activity. Our analysis shows that stimulus changes increase spiking rate while decreasing its variability. The inferred membrane potential statistics suggest that PPC neurons decrease their membrane potential variability in response to task relevant stimuli. Furthermore, more perceptually reliable stimuli lead to a larger decrease in membrane potential variability than less reliable ones. These findings suggest that individual cortical neurons track uncertainty, providing Bayesian benefits for downstream computations.

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bioRxiv2024

Transient DREADD manipulation of the dorsal Dentate Gyrus in rats impairs disambiguation of similar place-outcome associations

The dentate gyrus subfield of the hippocampus is thought to be critically involved in the disambiguation of similar episodic experiences and places in a context-dependent manner. However, most empirical evidence has come from lesion and gene knock-out studies in rodents, in which the dentate gyrus function is permanently perturbed and compensation of affected functions via other areas within the memory circuit could take place. The acute and causal role of the dentate gyrus herein remains therefore elusive. The present study aimed to investigate the acute role of the dorsal dentate gyrus in disambiguation learning using reversible inhibitory DREADDs. Rats were trained on a location discrimination task and learnt to discriminate between a rewarded and unrewarded location with either small (similar condition) or large (dissimilar condition) separation. Reward contingencies switched after a reversal rule, allowing us to track the temporal engagement of the dentate gyrus during the task. Bilateral but not unilateral DREADD modulation of the dentate gyrus impaired the initial acquisition learning of place-reward associations, but performance rapidly recovered to control levels within the same session. Modelling of the behavioural patterns revealed that reward learning and reward sensitivity were not associated with the DREADD-dependent impairment during acquisition learning, suggesting that either the ability to encode place-reward associations, or the fine-grained coding of place were instead affected. Our study thus provides novel evidence that the dorsal dentate gyrus is acutely and bilaterally engaged during the initial acquisition learning of ambiguous place-reward associations, although the exact neural mechanisms supporting this function still need to be fully understood.

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bioRxiv2023

The neural and computational architecture of feedback dynamics in mouse cortex during stimulus report

Conscious reportability of visual input is associated with a bimodal neural response in primary visual cortex (V1): an early-latency response coupled to stimulus features and a late-latency response coupled to stimulus report or detection. This late wave of activity, central to major theories of consciousness, is thought to be driven by prefrontal cortex (PFC), responsible for "igniting" it. Here we analyzed two electrophysiological studies in mice performing different stimulus detection tasks, and characterize neural activity profiles in three key cortical regions: V1, posterior parietal cortex (PPC) and PFC. We then developed a minimal network model, constrained by known connectivity between these regions, reproducing the spatio-temporal propagation of visual-and report-related activity. Remarkably, while PFC was indeed necessary to generate report-related activity in V1, this occurred only through the mediation of PPC. PPC, and not PFC, had the final veto in enabling the report-related late wave of V1 activity.

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bioRxiv2022

Triple dissociation of visual, auditory and motor processing in primary visual cortex

Primary sensory cortices respond to crossmodal stimuli, for example auditory responses are found in primary visual cortex (V1). However, it remains unclear whether these responses reflect sensory inputs or behavioural modulation through sound-evoked body movement. We address this controversy by showing that sound-evoked activity in V1 of awake mice can be dissociated into auditory and behavioural components with distinct spatiotemporal profiles. The auditory component began at [~]27 ms, was found in superficial and deep layers and originated from auditory cortex, as shown by inactivation by muscimol. Sound-evoked orofacial movements correlated with V1 neural activity starting at [~]80-100 ms and explained auditory frequency-tuning. Visual, auditory and motor activity were expressed by segregated neuronal populations and during simultaneous audiovisual stimulation, visual representations remained dissociable from auditory and motor-related activity. This threefold dissociability of auditory, motor and visual processing is central to understanding how distinct inputs to visual cortex interact to support vision.

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bioRxiv2021

Task complexity temporally extends the causal requirement for visual cortex in perception

The transformation of sensory inputs into behavioral outputs is characterized by an interplay between feedforward and feedback operations in cortical hierarchies. Even in simple sensorimotor transformations, recurrent processing is often expressed in primary cortices in a late phase of the cortical response to sensory stimuli. This late phase is engaged by attention and stimulus complexity, and also encodes sensory-independent factors, including movement and report-related variables. However, despite its pervasiveness, the nature and function of late activity in perceptual decision-making remain unclear. We tested whether the function of late activity depends on the complexity of a sensory change-detection task. Complexity was based on increasing processing requirements for the same sensory stimuli. We found that the temporal window in which V1 is necessary for perceptual decision-making was extended when we increased task complexity, independently of the presented visual stimulus. This window overlapped with the emergence of report-related activity and decreased noise correlations in V1. The onset of these co-occurring activity patterns was time-locked to and preceded reaction time, and predicted the reduction in behavioral performance obtained by optogenetically silencing late V1 activity (>200 ms after stimulus onset), a result confirmed by a second multisensory task with different requirements. Thus, although early visual response components encode all sensory information necessary to solve the task, V1 is not simply relaying information to higher-order areas transforming it into behavioral responses. Rather, task complexity determines the temporal extension of a loop of recurrent activity, which overlaps with report-related activity and determines how perceptual decisions are built.

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bioRxiv2021

Higher-order visual areas broaden stimulus responsiveness in mouse primary visual cortex

Over the past few years, the various areas that surround the primary visual cortex in the mouse have been associated with many functions, ranging from higher-order visual processing to decision making. Recently, some studies have shown that higher-order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here we studied how in vivo optogenetic inactivation of two higher-order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher-order visual areas similarly modulate early visual processing. In particular, these areas broaden stimulus responsiveness in the primary visual cortex, by amplifying sensory-evoked responses for stimuli not moving along the orientation preferred by individual neurons. Thus, feedback from higher-order visual areas amplifies V1 responses to non-preferred stimuli, which may aid their detection.

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bioRxiv2018

Functional determinants of enhanced and depressed inter-areal information flow in NREM sleep between neuronal ensembles in rat cortex and hippocampus

Compared to wakefulness, neuronal activity during non-REM sleep is characterized by a decreased ability to integrate information, but also by the re-emergence of task-related information patterns. To investigate the mechanisms underlying these seemingly opposing phenomena, we measured directed information flow by computing transfer entropy between neuronal spiking activity in three cortical regions and the hippocampus of rats across brain states. State-dependent information flow resulted to be jointly determined by the anatomical distance between neurons and by their functional specialization. We distinguished two regimes, operating at short and long time scales, respectively. From wakefulness to non-REM sleep, transfer entropy at short time scales increased for inter-areal connections between neurons showing behavioral task correlates. Conversely, transfer entropy at long time scales became stronger between non-task modulated neurons and weaker between task- modulated neurons. These results may explain how, during non-REM sleep, a global inter-areal disconnection is compatible with highly specific task-related information transfer.\n\nAuthor SummaryThe brain remains active during deep sleep, yet we still do not know which rules govern information processing between neurons across wakefulness and sleep. Here we provide a first study of how information flow at the level of spiking activity varies as a function of brain state, temporal scale, brain area and behavioral task correlates of single neurons. We found that inter-areal communication at millisecond time scales is enhanced during sleep compared to wakefulness between neurons that code for task information. Conversely, non-modulated neurons showed more prominent communication at longer time scales. These results indicate that multiple, functionally determined communicative architectures coexist in the brain, and provide a novel framework to understand information processing and its consequences during sleep.

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