Biology subjects

Bagur, S.

Publications and source records attributed to Bagur, S..

14 recordsLinked to original sources

bioRxiv2025

The geometry of cortical sound processing in slow wave sleep

During wake, sound-evoked and spontaneous neural activity of the auditory cortex evolve in distinct subspaces whereas anesthesia disrupts sound responses and merges these spaces. To evaluate if similar modifications of the sound representation geometry explain sensory disconnection during sleep, we followed large neural populations of the mouse auditory cortex across slow wave sleep and wakefulness. We observed that sleep dampens sound responses but preserves the geometry of sound representations which remain separate from spontaneous activity. Moreover, response dampening was strongly coordinated across neurons and varied throughout sleep spanning from fully preserved response patterns to population response failures on a fraction of sound presentations. These failures are more common during high spindle-band activity and more rarely observed in wakefulness. Therefore, in sleep, the auditory system preserves sound feature selectivity up to the cortex for detailed acoustic surveillance, but concurrently implements an intermittent gating mechanism leading to local sensory disconnections.

neuroscience↗

bioRxiv2025

Hippocampal reactivation of aversive experience enables safety learning and slow-breathing state for recovery from stress

Adaptive threat responses require both defensive behaviours to minimize danger and recovering from the induced physiological stress. However, the behavioural and neural basis of these recuperative strategies are still elusive. Using a novel two-location fear conditioning paradigm in mice, we have identified a slow-breathing immobility state of recovery that emerges when animals identify safe environments after threat avoidance. This immobile state was characterized by a 2-4 Hz breathing profile and replay of the aversive experience in the hippocampus. Suppressing hippocampal sharp-wave ripples (SWRs) inhibited the emergence of this recovery state, suggesting their role in learning safe locations. Anxiolysis with diazepam directly promoted the recovery state while suppressing SWRs, showing this treatment to be a double-edged sword that facilitates immediate relief but impairs long-term safety learning. These results demonstrate the importance of hippocampal replay for emotional resilience through its role in recovery.

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bioRxiv2025

Sound offset responses become highly informative in the auditory cortex

The entire auditory system downstream of the cochlea features pronounced offset responses, which follow the termination of sounds. Because of their ubiquity, it is still an unsolved question whether offset responses are generated early in the auditory system and then propagated or recomputed at each processing stage. Here, we analysed large-scale sound responses datasets acquired in the cochlear nucleus, inferior colliculus, medial geniculate nucleus and auditory cortex of awake mice. All brain regions showed a significant proportion of offset responses often combined with onset and sustained responses in the same neuron. However, using population activity decoders, we observed that neural representations after the sound offset show a three-fold increase in sound encoding accuracy in the cortex relative to subcortical areas. This result indicates that cortical offsets encode a more precise short-term memory of the elapsed sound than subcortical offsets and that they likely result from specific computational steps. Key points summaryO_LIOffset responses are found throughout the central auditory system C_LIO_LIOffset responses are often combined to sustained and onset responses at all central auditory system stages C_LIO_LIOffset responses provide richer information about elapsed sounds in the auditory cortex C_LI

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bioRxiv2025

Feature-dependent decorrelation of sound representations across the auditory pathway

AbstractEarly studies on orientation selectivity in the visual cortex have suggested that sensory systems generate new feature representations at specific processing stages. Many observations challenge this view, but in the absence of systematic, multistage measurements, the logic of how feature tuning emerges remains elusive. Here, using a generic approach based on representational similarity analysis with a noise-corrected population metric, we demonstrate in the mouse auditory system that feature representations evolve gradually with, in some cases, major, feature-specific improvements at particular stages. We observe that single frequency tuning is already fully developed in the cochlear nucleus, the first stage of processing, while tuning to higher-order features improves up to the auditory cortex, with major steps in the inferior colliculus for amplitude modulation frequency or noise bandwidth tuning and in the cortex for frequency modulation direction and for complex sound identity or direction. Moreover, we observe that intensity tuning is established in a feature-dependent manner, earlier for pure frequencies than for more complex sounds. This indicates that auditory feature computations are a mix of stepwise and gradual processes which together contribute to decorrelate sound representations.

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bioRxiv2024

Parallel mechanisms signal a hierarchy of sequence structure violations in the auditory cortex

The brain predicts regularities in sensory inputs at multiple complexity levels, with neuronal mechanisms that remain elusive. Here, we monitored auditory cortex activity during the local-global paradigm, a protocol nesting different regularity levels in sound sequences. We observed that mice encode local predictions based on stimulus occurrence and stimulus transition probabilities, because auditory responses are boosted upon prediction violation. This boosting was due to both short-term adaptation and an adaptation-independent surprise mechanism resisting anesthesia. In parallel, and only in wakefulness, VIP interneurons responded to the omission of the locally expected sound repeat at sequence ending, thus providing a chunking signal potentially useful for establishing global sequence structure. When this global structure was violated, by either shortening the sequence or ending it with a locally expected but globally unexpected sound transition, activity slightly increased in VIP and PV neurons respectively. Hence, distinct cellular mechanisms predict different regularity levels in sound sequences.

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bioRxiv2024

Massive perturbation of sound representations by anesthesia in the auditory brainstem

Anesthesia modifies sensory representations in the thalamo-cortical circuit, but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation in anesthesia is not possible based on awake activity. However, population level parameters, such as average tuning strength and population decoding accuracy are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing. TeaserAnesthesia compromises the normal transmission of sensory information as early as the first relay in the auditory system.

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bioRxiv2022

Distinction between slow waves and delta waves sheds light to sleep homeostasis and their association to hippocampal sharp waves ripples

Cortical slow waves and delta waves are hallmarks of NREM sleep and key elements in physiological processes such as memory consolidation and sleep homeostasis. However, no clear distinction has been made between the two types of electrophysiological events. We introduce a new distinction between slow waves, large amplitude waves on filtered LFP cortical signals, and delta waves, characterized by an inversion between deep and superficial layers and the co-occurrence with a cortical down state. Detection of slow waves, as large amplitude waves during NREM sleep, reveals that a large portion of them does not share the properties of delta waves and does not co-occur with cortical down states. Therefore, we distinguish type-1 slow waves, that are associated to a down state, from type-2 slow waves. We show that 1) only type-1 slow waves undergo strong homeostatic regulations and 2) type-2 slow waves create confusion about the temporal link with hippocampal sharp-wave ripples. Thus, we confirm that delta waves detected with our new method can be used as a proxy for down state. Altogether, this confirms the importance of a robust and accurate definition of delta waves to understand the fine neurophysiological mechanisms at stake during NREM sleep.

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bioRxiv2022

Social defeat induces REM sleep fragmentation through the PFC-VLPO pathway

The brainstem and hypothalamic structures implementing the daily cycles of wake, REM and NREM sleep have now been identified in remarkable detail. However, sleep structure dynamically adapts to environmental stressors, likely requiring top-down cortical feedback that is as yet unidentified. Here, we investigate the role of projections from prefrontal cortex (PFC), a key hub in stress regulation, to the ventro-lateral preoptic areas (VLPO), a master regulator of sleep states. Using ex vivo optogenetics, we demonstrate that activation of PFC terminals induces monosynaptic excitatory glutamatergic currents in VLPO NREM-promoting neurons. In vivo, activation of PFC-VLPO projections interrupts ongoing REM in favour of NREM, leading to fragmented REM bouts. Remarkably, chemogenetic inhibition of PFC-VLPO projections has no effect in baseline conditions but it blocks the REM fragmentation induced by Social Defeat Stress. Therefore, the PFC-VLPO pathway provides a top-down regulation specifically recruited in stressful conditions to induce short, fragmented REM bouts and favor NREM sleep.

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bioRxiv2022

Emergence of a time-independent population code in auditory cortex enables sound categorization and discrimination learning

The temporal structure of sensory inputs contains essential information for their interpretation by the brain1-9. Sensory systems represent these temporal cues through two codes: the temporal sequences of neuronal activity and the spatial patterns of neuronal firing rate3,7,10-20. However, it is still unknown which of these two coexisting codes causally drives sensory decisions3,10,20,21. To separate their contributions, we designed an optogenetic stimulation paradigm in the mouse auditory cortex to generate neuronal activity patterns differing exclusively along their temporal or spatial dimensions. Training mice to discriminate these patterns shows that they efficiently learn to discriminate spatial but not temporal patterns, indicating that spatial representations are necessary for sensory learning. In line with this result, we observed, based on large-scale neuronal recordings of the auditory system, that the auditory cortex is the first region in which spatial patterns efficiently represent temporal auditory cues varying over several hundred milliseconds. This feature is shared by the deep layers of neural networks trained to categorise time-varying sounds. Therefore, the emergence of a spatial code for temporal sensory cues is a necessary condition to associate temporally structured stimuli to decisions. We expect this constraint to be crucial for re-engineering perception by cortical stimulation.

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bioRxiv2022

Enhanced performance in perceptual decision making task without deprivation in mice using medial forebrain bundle stimulation

Training animals on perceptual decision-making tasks is essential to many fields of neuroscience. Current protocols generally use water as a reward in water-deprived animals. This can be challenging since it requires balancing animals deprivation level with their well-being. Moreover, trial number is limited once they reach satiation. Here, we present electrical stimulation of the medial forebrain bundle (MFB) as an alternative reward in mice that avoids deprivation entirely while yielding stable motivation for thousands of trials. We trained MFB rewarded mice to perform a series of auditory discrimination tasks using either licking or lever pressing as a behavioural report. MFB animals learnt tasks at similar speed to water-deprived mice and more reliably reached higher overall accuracy in harder tasks. Moreover, they performed up to 3800 trials within a session without loss of motivation. Importantly, MFB stimulation does not impact the sensory behaviour under study since psychometric parameters and response times are preserved. Finally, in accordance with the lack of deprivation, MFB mice lack signs of metabolic or behavioural stress compared to water-deprived mice (weight loss, open field, home cage behaviour). Overall, using MFB stimulation as a reward is a highly promising tool for task learning since it enhances task performance whilst avoiding deprivation.

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bioRxiv2018

Improved sleep scoring in mice reveals human-like stages.

Rodents are the main animal model to study sleep. Yet, in spite of a large consensus on the distinction between rapid-eye-movements sleep (REM) and non-REM sleep (NREM) in both humans and rodent, there is still no equivalent in mice of the NREM subdivision classically described in humans.\n\nHere we propose a classification of sleep stages in mice, inspired by human sleep scoring. By using chronic recordings in medial prefrontal cortex (mPFC) and hippocampus we can classify three NREM stages with a stage N1 devoid of any low oscillatory activity and N3 with a high density of delta waves. These stages displayed the same evolution observed in human during the whole sleep or within sleep cycles. Importantly, as in human, N1 in mice is the first stage observed at sleep onset and is increased after sleep fragmentation in Orexin-/- mice, a mouse model of narcolepsy.\n\nWe also show that these substages are associated to massive modification of neuronal activity. Moreover, considering these stages allows to predict mPFC neurons evolution of firing rates across sleep period. Notably, neurons preferentially active within N3 decreased their activity over sleep while the opposite is seen for those preferentially active in N1 and N2.\n\nOverall this new approach shows the feasibility of NREM sleep sub-classification in rodents, and, in regard to the similarity between sleep in both species, will pave the way for further studies in sleep pathologies given the perturbation of specific sleep substages in human pathologies such as insomnia, somnambulism, night terrors, or fibromyalgia.

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bioRxiv2018

Dissociation of fear initiation and maintenance by breathing-driven prefrontal oscillations

Does the body play an active role in emotions? Since the original James/Cannon controversy this debate has mainly been fueled by introspective accounts of human experience. Here, we use the animal model to demonstrate a physiological mechanism for bodily feedback and its causal role in the stabilization of emotional states. We report that during fear-related freezing mice breathe at 4Hz and show, using probabilistic modelling, that optogenetic perturbation of this feedback specifically reduces freezing maintenance without impacting its initiation. This rhythm is transmitted by the olfactory bulb to the prefrontal cortex where it organizes neural firing and optogenetic probing of the circuit demonstrates frequency-specific tuning that maximizes prefrontal cortex responsivity at 4Hz, the breathing frequency during freezing. These results point to a brain-body-brain loop in which the initiation of emotional behavior engenders somatic changes which then feedback to the cortex to directly participate in sustaining emotional states.

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bioRxiv2017

Task Engagement Enhances Population Encoding of Stimulus Meaning in Primary Auditory Cortex

The main functions of primary sensory cortical areas are classically considered to be the extraction and representation of stimulus features. In contrast, higher cortical sensory association areas are thought to be responsible for combining these sensory representations with internal motivations and learnt associations. These regions generate appropriate neural responses that are maintained until a motor command is executed. Within this framework, responses of the primary sensory areas during task performance are expected to carry less information about the behavioral meaning of the stimulus than higher sensory, association, motor and frontal cortices. Here we demonstrate instead that the neuronal population responses in the early primary auditory cortex (A1) display many aspects of responses generally associated with higher-level areas. A1 activity was recorded in awake ferrets while they were either passively listening or actively discriminating two periodic click trains of different rates in a Go/No-Go paradigm. By applying population-level dimensionality reduction techniques, we found that task-engagement induced a shift in the nature of the encoding from a sensory-driven representation of the two stimuli to a behaviorally relevant representation of the two categories that specifically enhances the target stimulus. We demonstrate that this shift in encoding relies partly on a novel mechanism of change in spontaneous activity patterns upon engagement in the task. We show that this population-level representation of stimuli in A1 population activity bears strong similarities to responses in the frontal cortex, but appears earlier following stimulus presentation. Analysis of neural activity recorded in various Go/No-Go tasks, with different sounds and reinforcement paradigms, reveals that this striking population-level enhancement of target representation is a general property of task engagement. These findings indicate that primary sensory cortices play a highly flexible role in the processing of incoming stimuli and implement a crucial change in the structure of population activity in order to extract task-relevant information during behavior.

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bioRxiv2017

Harnessing sleep/wake state tracking by olfactory bulb oscillations to perform fully brain-based sleep scoring in mice

It has long been thought that sleep scoring could not be achieved with brain signals alone despite the deep neuromodulatory transformations that accompany sleep state changes. Here we demonstrate using multi-site electrophysiological LFP recordings in freely moving mice that gamma power in the olfactory bulb (OB) allows for clear classification of sleep and wake. Coupled with hippocampal theta activity, it allows the construction of a sleep scoring algorithm that relies on brain activity alone. This method reaches over 90% homology with classical methods based on muscular activity (EMG) and video tracking. Moreover, contrary to EMG, OB gamma power allows correct discrimination between sleep and immobility in ambiguous situations such as fear-related freezing. We use the instantaneous power of hippocampal theta oscillation and OB gamma oscillation to construct a 2D phase-space that is highly robust across mice and days. Dynamic analysis of trajectories within this space yields a novel characterization of sleep/wake and wake/sleep transitions as deeply divergent phenomena. Whereas waking up is a fast and direct transition, falling asleep is best described as stochastic and gradual change. Altogether this methodology opens the avenue for multi-timescale characterization of sleep states with high temporal resolution based on brain signals only.

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