Biology subjects

Bathellier, B.

Publications and source records attributed to Bathellier, B..

16 recordsLinked to original sources

bioRxiv2025

Cortical neuroprostheses improve auditory coding and perception compared to cochlear implants

Cochlear implants have transformed the treatment of hearing loss by enabling auditory perception through direct electrical stimulation of the auditory nerve. However, their effectiveness can be limited in noisy environments, for fine frequency resolution, and in patients lacking an intact auditory nerve. The auditory cortex offers a promising alternative target for neuroprosthetic stimulation, but it remains unclear whether direct cortical input can evoke percepts with the complexity and structure of natural sounds. Here we show that surface cortical implants in mice support robust and flexible auditory behaviour, surpassing cochlear implants in tasks requiring fine spectral, temporal, and noise-resistant discrimination. We also show that animals generalize seamlessly between cortical and acoustic stimuli without additional training, indicating that cortical stimulation can generate interpretable, sound-like percepts. Electrophysiological recordings revealed that cortical stimulation drives spatially and temporally structured neural activity in auditory cortex, resembling responses to natural sound. These findings establish that the auditory cortex can interpret spatially and temporally patterned electrical input in a behavioural relevant way. By linking neuroprosthetic stimulation to naturalistic neural representations and behavioural generalization, this work provides a mechanistic and functional foundation for cortical auditory neuroprostheses and points toward new strategies for restoring hearing through direct brain stimulation.

neuroscience↗

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

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

neuroscience↗

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.

neuroscience↗

bioRxiv2025

Chronically implantable μLED arrays for optogenetic cortical surface stimulation in mice

Cortical implants are a proven clinical neurotechnology with the potential to transform our understanding of cognitive processes. These processes rely on complex neuronal networks that are difficult to selectively probe or stimulate. Optogenetics offers cell-type specificity, but achieving the density and coverage required for chronic, high-resolution modulation remains a challenge. Here we present a 100-element {micro}LED array (200 {micro}m pixel pitch, 2 x 2 mm2 footprint) coupled into a miniaturised, flexible system suitable for chronic implantation and optogenetic stimulation of the surface of the mouse cortex. The {micro}LEDs can remain stable for over 300 hours continuous operation time in-vivo, allowing for months-long chronic experiments. Simultaneous electrophysiology recordings confirmed robust neuronal responses corresponding to low {micro}LED drive currents (<5 mA), minimising thermal effects and supporting future wireless operation. The spatial resolution of neuronal responses was consistent with a simulated model of light scattering in the cortical layers, enabling device optimisation. Behavioural experiments with chronically implanted mice demonstrated robust learning during discrimination tasks using spatially distinct optogenetic stimulation patterns.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2022

Effective sound localization coding by noisy populations of mouse inferior colliculus neurons revealed by fast volumetric imaging

Sound location coding has been extensively studied at the central nucleus of the mammalian inferior colliculus (CNIC), supporting a population code. However, this population code has not been extensively characterized on the single-trial level with simultaneous recordings or at other anatomical regions like the dorsal cortex of inferior colliculus (DCIC), which is relevant for learning-induced experience dependent plasticity. To address these knowledge gaps, here we made in two complementary ways large-scale recordings of DCIC populations from awake mice in response to sounds delivered from 13 different frontal horizontal locations (azimuths): volumetric two-photon calcium imaging with [~]700 cells simultaneously recorded at a relatively low temporal resolution, and high-density single-unit extracellular recordings with [~]20 cells simultaneously recorded at a high temporal resolution. Independent of the method, the recorded DCIC population responses revealed substantial trial-to-trial variation (neuronal noise) which was significantly correlated across pairs of neurons (noise correlations) in the passively listening condition. Nevertheless, decoding analysis supported that these noisy response patterns encode sound location on the single-trial basis, reaching errors that match the discrimination ability of mice. The detected noise correlations contributed to minimize the error of the DCIC population code of sound azimuth. Altogether these findings point out that DCIC can encode sound location in a similar format to what has been proposed for CNIC, opening exciting questions about how noise correlations could shape this code in the context of cortico-collicular input and experience dependent plasticity.

neuroscience↗

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.

neuroscience↗

bioRxiv2022

Subcortical and cortical tracking of communication sound envelopes in challenging listening conditions

Humans and animals constantly face challenging acoustic environments such as various background noises restricting the detection, discrimination and identification of behaviorally salient sounds. Here, we disentangled the role of temporal envelope tracking on the decrease in neuronal and behavioral discrimination between communication sounds in situations of acoustic degradations. We simulated responses of auditory nerve fibers and recorded neuronal activity in cochlear nucleus, inferior colliculus, thalamus and auditory cortex in anesthetized guinea-pigs. Furthermore, a Go/No-Go sound discrimination task involving two of the guinea-pig whistles was performed on mice in silence and noise. For all conditions, we found that auditory neurons better track the slow amplitude modulations (<20 Hz) of the stimulus envelopes than the faster ones. In addition, the decrease in neuronal and behavioral discrimination performance in noise can be explained by an increased similarity of the vocalization envelopes in the low frequency range (<20 Hz). Together, these results suggest that slow envelope tracking is a general property of auditory neurons, and any difference between the slow envelopes of natural stimuli allows coping with degraded conditions.

neuroscience↗

bioRxiv2021

Awake perception is associated with dedicated neuronal assemblies in cerebral cortex

Neural activity in sensory cortex combines stimulus responses and ongoing activity, but it remains unclear whether they reflect the same underlying dynamics or separate processes. Here we show that during wakefulness, the neuronal assemblies evoked by sounds in the auditory cortex and thalamus are specific to the stimulus and distinct from the assemblies observed in ongoing activity. In contrast, we observed in three different anesthesia, that evoked assemblies are indistinguishable from ongoing assemblies in the cortex. However, they remain distinct in the thalamus. A strong remapping of sensory responses accompanies this dynamical state change produced by anesthesia. Together, these results show that the awake cortex engages dedicated neuronal assemblies in response to sensory inputs, which we suggest is a network correlate of sensory perception.

neuroscience↗

bioRxiv2020

Rapid reformatting of the cortical code during active tactile discrimination

Touch-based object recognition relies on perception of compositional tactile features like roughness, shape, and surface orientation. However, besides roughness, it remains unclear how these different tactile features are encoded to guide perception. Here, we establish a barrel cortex-dependent perceptual task in which mice discriminate tactile gratings based on orientation using only their whiskers. Multi-electrode recordings in barrel cortex reveal weak orientation tuning in average firing rates during grating exploration despite high levels of cortical activity. Just before decision, orientation information extracted from fast cortical dynamics more closely resembles concurrent psychophysical measurements than single neuron orientation tuning curves. This temporal code conveys both stimulus and choice-related information, suggesting that fast cortical dynamics during exploration of a tactile object both reflect the physical stimulus and impact the upcoming perceptual decision of the animal.

animal behavior and cognition↗

bioRxiv2019

Population coding and network dynamics during OFF responses in auditory cortex

Across sensory systems, complex spatio-temporal patterns of neural activity arise following the onset (ON) and offset (OFF) of stimuli. While ON responses have been widely studied, the mechanisms generating OFF responses in cortical areas have so far not been fully elucidated. We examine here the hypothesis that OFF responses are single-cell signatures of recurrent interactions at the network level. To test this hypothesis, we performed population analyses of two-photon calcium recordings in the auditory cortex of awake mice listening to auditory stimuli, and compared linear single-cell and network models. While the single-cell model explained some prominent features of the data, it could not capture the structure across stimuli and trials. In contrast, the network model accounted for the low-dimensional organisation of population responses and their global structure across stimuli, where distinct stimuli activated mostly orthogonal dimensions in the neural state-space.

neuroscience↗

bioRxiv2018

Cortical recruitment determines learning dynamics and strategy

Salience is a broad and widely used concept in neuroscience whose neuronal correlates, however, remain elusive. In behavioral conditioning, salience is used to explain various effects, such as stimulus overshadowing, and refers to how fast and strongly a stimulus can be associated with a conditioned event. Here, we show that sounds of diverse quality, but equal intensity and perceptual detectability, can recruit different levels of population activity in mouse auditory cortex. When using these sounds as cues in a Go/NoGo discrimination task, the degree of cortical recruitment matches the salience parameter of a reinforcement learning model used to analyze learning speed. We test an essential prediction of this model by training mice to discriminate light-sculpted optogenetic activity patterns in auditory cortex, and verify that cortical recruitment causally determines association or overshadowing of the stimulus components. This demonstrates that cortical recruitment underlies major aspects of stimulus salience during reinforcement learning.

neuroscience↗

bioRxiv2018

Context-dependent signaling of coincident auditory and visual events in primary visual cortex

Detecting rapid coincident changes across sensory modalities is essential to recognize sudden threats and events. Using two-photon calcium imaging in identified cell types in awake mice, we show that auditory cortex (AC) neurons projecting to primary visual cortex (V1) preferentially encode the abrupt onsets of sounds. In V1, a sub-population of layer 1 interneurons gates this selective cross-modal information by a suppression specific to the absence of visual inputs. However, when large auditory onsets coincide with visual stimuli, visual responses are strongly boosted in V1. Thus, a dynamic asymmetric circuit across AC and V1 specifically identifies visual events starting simultaneously to sudden sounds, potentially catalyzing localization of new sound sources in the visual field.

neuroscience↗