Biology subjects

Sibille, J.

Publications and source records attributed to Sibille, J..

15 recordsLinked to original sources

bioRxiv2026

Coordinated orienting behavior emerges following unilateral optogenetic activation of Superior Colliculus GABAergic neurons

Orienting coordinates movements of the eyes, whiskers, nose, and other effectors, but how the superior colliculus (SC) recruits these components over time remains unclear. We combined unilateral optogenetic activation of SC GABAergic neurons with high-speed tracking of facial movements and Neuropixels recordings to examine SC-evoked orienting in head-fixed mice. Stimulation recruited movements of the whiskers, nose, eyes, and pupil. Horizontal eye and nose movements were directed contralateral to the stimulated hemisphere, whereas vertical eye movements, pupil dilation, and whisker protraction did not differ significantly between stimulation sides. Nose and whisker movements generally preceded eye movements, followed by slower pupil dilation, revealing a temporally organized response. Recordings from the SC contralateral to the stimulated hemisphere revealed heterogeneous neuronal responses comprising short-latency excitation and delayed excitation or inhibition. Short-latency excitation was similar on trials with and without evoked movements, whereas delayed excitation was greater on trials that evoked eye or nose movements. Neurons modulated during spontaneous nose movements showed corresponding optogenetically evoked responses, linking stimulation-induced activity to endogenous movement-related activity. Thus, activation of SC GABAergic neurons initiates evolving population activity that recruits a coordinated sequence of orienting movements.

neuroscience↗

bioRxiv2026

Thalamocortical, not Intracortical, Inputs Set the Wakeful Activity Levels of Cortical Visual Inhibition

Cortical neurons integrate from a wide range of synaptic inputs, locally within the cortex and distally from multiple brain sources, which altogether support the generation and transmission of spikes. Yet, the relative influence on local cortical processing between thalamocortical and intracortical inputs still remains poorly understood. Here, we used tangential insertion of high-density silicon probes to capture thalamocortical next to intracortical functional connectivity, thereby unraveling their relative contribution to local cortical dynamics. By comparing wakefulness versus light anesthesia, we revealed a marked wakeful increase of firing in specifically thalamocortical axons and putative cortical inhibitory neurons; an increase which is very homogeneous in both populations, and comparatively absent in neighboring cortical excitatory neurons. Such specific comodulation is attributable to the known preferential connectivity of thalamocortical axons toward putative cortical inhibitory neurons, which we quantified to follow a 90/10% preference. In addition, we uncovered that wakeful increases of activity levels are symmetric in thalamocortical synapses and asymmetric in intracortical synapses. Indeed, within intracortical synapses, the wakeful increases of firing mostly happen in receiving neurons, leaving pre-synaptic upstream neurons barely impacted by wakefulness. In the meantime, thalamocortical receiving excitatory neurons exhibit a marked wakeful increase of firing, unlike the rest of the excitatory cortical population. Using mathematical modelling simulating spike transmission in thalamocortical and intracortical networks, we showed that only outnumbering thalamocortical-to-intracortical inputs could mimic the observed homogeneous wakeful increases of firing in thalamocortical and cortical inhibitory neurons. Altogether, our results identify thalamocortical synaptic inputs as a key controller of the wakeful level of firing of inhibitory neurons at the first relay of visual cortical processing.

neuroscience↗

bioRxiv2026

Synergistic effects of presynaptic and postsynaptic neurons give rise to three-stage short-term plasticity in vivo

Short-term plasticity (STP) is the transient fluctuation of connection strength between two neurons depending on the recent history of neuronal activity. STP shapes neurotransmission over time and plays important roles in circuit computations. It is classically quantified ex vivo either at the synaptic level or at the level of spike transmission from the presynaptic neuron to the postsynaptic neuron. However, the exact relationship between the postsynaptic dendritic responses and spike transmission during STP still remains unclear in vivo. Here, we characterized together the STP of both postsynaptic dendritic responses, measured by the postsynaptic field potential (PFP), and spike transmission at the retinocollicular pathway of mice. We found mostly facilitating STP, where the second presynaptic spike occurring within 25 ms induces a larger PFP, and consequently a higher postsynaptic firing rate compared to responses from the first presynaptic spike. Both PFP and spike transmission exhibit short-term facilitation, but to a different degree, where the facilitation in the spike transmission is larger than the PFP. The PFP and spike transmission also exhibit facilitation of different decay time constants, indicating a nonlinear relationship between the two. Interestingly, a preceding postsynaptic spike can induce a similarly large but longer lasting facilitation on the spike transmission upon receiving a subsequent presynaptic input. However, STP of the PFP does not depend on the preceding postsynaptic spike, suggesting that this longer postsynaptic facilitation has a nonsynaptic origin. Overall, our results indicate that STP of the retinocollicular pathway exhibits three different stages: 1) a weak synaptic facilitation of postsynaptic dendritic responses, 2) a strong synaptic facilitation of spike transmission, and 3) a longer lasting nonsynaptic facilitation of spike transmission. Using a computational model, we show that the second STP stage is a direct inheritance from the first STP stage, whereas two opposing nonsynaptic mechanisms with different time constants are needed for the emergence of the third STP stage. These findings provide direct evidence that synaptic and nonsynaptic STPs coexist in vivo, paving the way for large-scale measurement of these STPs and offering a means to monitor the transmission of information in neural circuits of behaving animals.

neuroscience↗

bioRxiv2026

Hippocampal tangential insertions of high-density silicone probes in head-fixed mice enhance spatial sampling

The hippocampus is a key structure within the medial temporal lobe which plays a central role in the formation and consolidation of declarative memories. Despite technological progress, a full understanding of hippocampal rhythms, neuronal population activity, and the underlying connectivity remains elusive, partly due to its complex morphology in a croissant-like shape which limits coronal and sagittal approaches. To address this limitation, we propose two different tangential insertions of high-density electrode probes (Neuropixels 1.0) aligned to either the dorsal or ventral sections of the hippocampus. Each approach enables the placement of up to 384 recording sites within the hippocampal formation. Both insertions are performed in head-fixed conditions, which can be easily combined with detailed monitoring of the animals behavioral states including spontaneous running and facial movements. The two proposed tangential dorsal and ventral insertions capture almost continuously the physiology of the hippocampus across 3.84 mm of tissue. We show that when placed across the pyramidal layer, such insertions can harness ripple oscillations from approximately 130 channels, corresponding to about [~]1.3 mm of tissue, with a coverage of 2 channels every 20 {micro}m. Furthermore, such insertions enabled us to record up to 400 hippocampal neurons simultaneously from a single probe, endowing us with the capability to capture putative functionally connected neuronal pairs. Although the conventional orthogonal/vertical approach is optimal for recording the laminar organization of hippocampal activity, we demonstrate how, for the longitudinal axis of hippocampus, tangential insertions can substantially increase spatial reach and sampling resolution, enabling a more detailed description of activity along this axis.

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bioRxiv2025

Thalamocortical coupling and cortical E-I balance generate diverse anesthetic α-spindles for interpretable EEG decoding

The neuronal circuits generating frequency (8-13Hz) oscillatory patterns during anesthesia are poorly understood, making their use difficult in predictive medicine. Here, we combine large-scale in vivo recordings of thalamocortical neuronal ensembles in anesthetized mice with a minimal neural mass model. We report non-rhythmic, weakly synchronized firing of thalamic and cortical neurons correlated with oscillatory patterns, indicating an emergent network rather than cellular dynamics. The associated imbalance between the firing of excitatory and inhibitory cortical neurons, together with an increase in firing fluctuations, favors larger amplitudes oscillations, whereas changes in thalamic neuron output control oscillation frequency. A neural mass model, comprising reciprocally connected excitatory and inhibitory cortical and thalamic neurons well reproduces the oscillation patterns observed in vivo at increasing anesthetic doses. These results provide a direct link between EEG oscillations during anesthesia and their underlying network/cellular dynamics which are well captured by a computational model that is clinically relevant for anesthetized brain state monitoring. HighlightsO_LI transient patterns during anesthesia emerge from thalamocortical and cortical excitatory-inhibitory (E-I) network dynamics. C_LIO_LI pattern frequency and amplitude reflect depth of anesthesia, dynamic thalamocortical equilibrium and E-I imbalance. C_LIO_LIEmergence of spindle-like patterns at multiple frequency defines newly characterized brain-state during anesthesia C_LIO_LIA mass-model reproduces the transient nature and spectral diversity of anesthetic-induced oscillations, linking neural circuit mechanisms to EEG output. C_LI

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bioRxiv2025

Sequential visual stimuli increase high frequency power in the visual cortex

Today, 40 Hz flickering full-field visual stimulation is used to entrain neuronal oscillations for a variety of therapeutic purposes. We here propose spatially organized sequential visual flickering stimulation as a newer tool to entrain the visual system. We show that sequential visual flickering can evoke increased power in high frequencies (100 to 190 Hz) in the visual cortex of mice. Consequently, sequential sensory stimulation should be regarded as a putative new way leading to power increases in high frequency domains.

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bioRxiv2024

Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking

Beyond the vast array of functional roles attributed to serotonin (5-HT) in the brain, changes in 5-HT levels have been shown to accompany changes in behavioral states, including WAKE, NREM and REM sleep. Whether 5-HT dynamics at shorter time scales can be seen to delineate substates within these larger brain states remains an open question. Here, we performed simultaneous recordings of extracellular 5-HT using a recently-developed G Protein-Coupled Receptor-Activation-Based 5-HT sensor (GRAB5-HT3.0) and local field potential (LFP) in the hippocampal CA1, which revealed the presence of prominent ultraslow (<0.05 Hz.) 5-HT oscillations both during NREM and WAKE states. Interestingly, the phase of these ultraslow 5-HT oscillations was found to distinguish substates both within and across larger behavioral states. Hippocampal ripples occurred preferentially on the falling phase of ultraslow 5-HT oscillations during both NREM and WAKE, with higher power ripples concentrating near the peak specifically during NREM. By contrast, hippocampal-cortical coherence was strongest and microarousals and intracranial EMG peaks were most prevalent during the rising phase in both wake and NREM. Overall, ultraslow 5-HT oscillations delineate substates within the larger behavioral states of NREM and WAKE, thus potentially temporally segregating internal memory consolidation processes from arousal-related functions.

neuroscience↗

bioRxiv2024

Differential Short-Term Facilitation Of Synaptic Inputs And Spike Transmission At The Retinocollicular Synapse In Vivo

Short-term plasticity (STP) is important for understanding how neuronal circuits can perform different computations. The STP of a neuron pair can be measured directly using paired whole-cell recordings. Besides, the cross-correlation between the presynaptic and postsynaptic neuronal firing is usually used as a proxy for estimating the synaptic properties. However, the relationships between the synaptic inputs and the spiking properties of the postsynaptic neurons during the STP in vivo still remain unclear. Here, we characterized the STP of both synaptic input, measured by the postsynaptic field potential (PFP), and spike transmission at the retinocollicular pathway of mice. We found that the STP of the retinocollicular pathway is mainly facilitating, where the second presynaptic spike induces a larger PFP and higher postsynaptic firing rate than the first presynaptic spike. The facilitation in the postsynaptic firing rate is generally larger than the PFP facilitation. Interestingly, the last postsynaptic spike timing also has a large facilitating effect on the postsynaptic spiking upon receiving a presynaptic input spike. However, the PFP does not depend on the last postsynaptic spike timing, suggesting that there is an input-independent component of spike transmission in STP. Overall, our results indicate that the STP of the retinocollicular pathway is likely a two-stage process, where the spiking plasticity of the postsynaptic neuron could be independent of its inputs. HighlightsO_LIMeasure the short-term plasticity of the postsynaptic dendritic response and the spike transmission simultaneously C_LIO_LIThe retinocollicular pathway exhibits paired-spike facilitation C_LIO_LISpike transmission facilitates more than postsynaptic dendritic response C_LIO_LIShort last postsynaptic spike time facilitates spike transmission independent of the next presynaptic input C_LI

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bioRxiv2023

Retinal input integration in excitatory and inhibitory neurons in the mouse superior colliculus in vivo

The superior colliculus (SC) is a midbrain structure that contains one of the highest densities of inhibitory neurons in the brain and, together with the thalamocortical visual system, it plays a key role in visually guided behaviors. The SC receives direct inputs from retinal ganglion cells (RGCs) but whether excitatory and inhibitory SC neurons differentially integrate retinal activity in vivo is still largely unknown. We recently established an extracellular recording approach using high-density electrodes to measure the activity of RGCs simultaneously with their postsynaptic SC targets in vivo, that allows addressing how SC neurons integrate RGC activity. Here, we employ this method to study the functional properties and dynamics that govern retinocollicular signaling in a cell-type specific manner by identifying GABAergic SC neurons using optotagging in anesthetized VGAT- ChR2 mice. We measured 305 monosynaptically connected RGC-SC pairs, out of which approximately one third of retinal afferents connect onto inhibitory SC neurons. We show that both excitatory and inhibitory SC neurons receive comparably strong RGC inputs, with functionally similar RGC-SC pairs showing stronger connections. Our results demonstrate that similar wiring rules apply for RGCs innervation of both excitatory and inhibitory SC neurons, which is unlike the cell-type specific connectivity in the thalamocortical system. Contrasting the similar RGC-SC connection strength, we observed that RGC activity contributed more to the activity of postsynaptic excitatory SC neurons than to the activity of postsynaptic inhibitory SC neurons. This implies that the excitatory SC neurons are more specifically coupled to RGC afferent inputs, while inhibitory SC neurons may integrate additional inputs from other sources. Taken together, our study deepens the understanding of cell-type specific retinocollicular functional connectivity and emphasizes that the two major brain areas for visual processing, the visual cortex and the superior colliculus, differently integrate sensory afferent inputs.

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bioRxiv2022

Efficient mapping of the thalamocortical monosynaptic connectivity in vivo by tangential insertions of high-density electrodes in cortex

Thalamus provides the principal input to cortex, thus understanding the mechanisms of cortical computations in behaving animals requires to characterize the thalamocortical connectivity in vivo. We show that tangential insertions of high-density electrodes into mouse cortex capture the activity of thalamocortical axons simultaneously with their synaptically connected cortical neurons. Multiple thalamic synaptic inputs to cortical neurons can be measured providing an efficient approach for mapping the thalamocortical connectivity in vivo.

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bioRxiv2022

Retinal waves align the concentric orientation map in mouse superior colliculus to the center of vision

Neurons in the mouse superior colliculus (SC) are arranged in an orientation preference map that has a concentric organization, which is aligned to the center of vision and the optic flow experienced by the mouse. The developmental mechanisms that underlie this functional map remain unclear. Here, we propose that the spatiotemporal properties of spontaneous retinal waves during development provide a scaffold to establish the concentric orientation map in the mouse SC and its alignment to the optic flow. We test this hypothesis by modelling the orientation-tuned SC neurons that receive ON/OFF retinal inputs. Our results suggest that the stage III retinal wave properties, namely OFF delayed response and the wave propagation direction bias, are key factors that regulate the spatial organization of the SC orientation map. Specifically, the OFF delay mediates the establishment of orientation-tuned SC neurons by segregating their ON/OFF receptive subfields, the wave-like activities facilitate the formation of a concentric pattern, and the wave direction biases align the orientation map to the center of vision. Taken together, our model suggests that retinal waves may play an instructive role in establishing functional properties of SC neurons and provides a promising mechanism for explaining the correlations between the optic flow and the SC orientation map.

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bioRxiv2022

Absence of the fragile X mental retardation protein alters response patterns to sounds in the auditory midbrain

Among the different autism spectrum disorders, Fragile X Syndrome (FXS) is the most common inherited cause of mental retardation. Sensory and especially auditory hypersensitivity is a key symptom in patients, which is well mimicked in the Fmr1 -/- mouse model. However, the physiological mechanisms underlying FXSs acoustic hypersensitivity in particular remain poorly understood. Here, we categorized spike response patterns to pure tones of different frequencies and intensities from neurons in the Inferior Colliculus (IC), a central integrator in the ascending auditory pathway. Based on this categorization we analyzed differences in response patterns between IC neurons of WT and Fmr1 -/- mice. Our results report broadening of frequency tuning, an increased firing in response to monaural as well as binaural stimuli, an altered balance of excitation-inhibition, and reduced response latencies, all expected features of acoustic hypersensitivity. Furthermore, we were surprised to notice that all neuron response types in Fmr1 -/- mice displayed enhanced offset-rebound activity outside their excitatory frequency response area. These results provide evidence that the loss of Fmr1 not only increases spike responses in IC neurons similar to auditory brainstem neurons, but also changes response patterns such as offset spiking. One can speculate this to be an underlying aspect of the receptive language problems associated with Fragile X syndrome.

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bioRxiv2021

Strong and specific connections between retinal axon mosaics and midbrain neurons revealed by large scale paired recordings

The superior colliculus (SC) is a midbrain structure that plays important roles in visually guided behaviors. Neurons in the SC receive afferent inputs from retinal ganglion cells (RGC), the output cells of the retina, but how SC neurons integrate RGC activity in vivo is unknown. SC neurons might be driven by strong but sparse retinal inputs, thereby reliably transmitting specific retinal functional channels. Alternatively, SC neurons could sum numerous but weak inputs, thereby extracting new features by combining a diversity of retinal signals. Here, we discovered that high-density electrodes simultaneously capture the activity and the location of large populations of retinal axons and their postsynaptic SC target neurons, permitting us to investigate the retinocollicular circuit on a structural and functional level in vivo. We show that RGC axons in the mouse are organized in mosaics that provide a single cell precise representation of the retina as input to SC. This isomorphic mapping between retina and SC builds the scaffold for highly specific wiring in the retinocollicular circuit which we show is characterized by strong connections and limited functional convergence, established in log-normally distributed connection strength. Because our novel method of large-scale paired recordings is broadly applicable for investigating functional connectivity across brain regions, we were also able to identify retinal inputs to the avian optic tectum of the zebra finch. We found common wiring rules in mammals and birds that provide a precise and reliable representation of the visual world encoded in RGCs to neurons in retinorecipient areas. HIGHLIGHTSO_LIHigh-density electrodes capture the activity of afferent axons and target neurons in vivo C_LIO_LIRetinal ganglion cells axons are organized in mosaics C_LIO_LISingle cell precise isomorphism between dendritic and axonal RGC mosaics C_LIO_LIMidbrain neurons are driven by sparse but strong retinal inputs C_LIO_LIFunctional wiring of the retinotectal circuit is similar in mammals and birds C_LI

neuroscience↗

bioRxiv2021

Tangential high-density electrode insertions allow to simultaneously measure neuronal activity across an extended region of the visual field in mouse superior colliculus

The superior colliculus (SC) is a midbrain structure that plays a central role in visual processing. Although we have learned a considerable amount about the function of single SC neurons, the way in which sensory information is represented and processed on the population level in awake behaving animals and across a large region of the retinotopic map is still largely unknown. Partially because the SC is anatomically located below the cortical sheet and the transverse sinus, it is technically difficult to measure neuronal activity from a large population of neurons in SC. To address this, we propose a tangential recording configuration using high-density electrode probes (Neuropixels) in mouse SC in vivo that permits a large number of recording sites (~200) accessibility inside the SC circuitry. This approach thereby provides a unique opportunity to measure the activity of SC neuronal populations composing up to ~2 mm of SC tissue and characterized by receptive fields covering an extended region in the visual field. Here we describe how to perform tangential recordings along the anterior-posterior and the medio-lateral axis of the mouse SC in vivo and how to combine this approach with optogenetic tools for cell-type identification on the population level.

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bioRxiv2018

Dynamics of ion fluxes between neurons, astrocytes and the extracellular space during neurotransmission

Ionic homeostasis in the brain involves redistribution of ionic fluxes in several cell types and compartments, including neurons, astrocytes and the extracellular space. How the major ionic activity-dependent fluxes of potassium and sodium are individually regulated remains difficult to dissociate and to track experimentally. We here review recent progress in modeling the ionic fluxes evoked by neuronal activity based on mass conservation. Excitability of neurons indeed relies on inward sodium and outward potassium fluxes during action potential firing. Recently, we have developed a tri-compartment model based on mass-action kinetics equations that account for potassium dynamics between neurons, astrocytes and the extracellular space. This review describes how such type of model can be used to spatially and temporally predict potassium fluxes during various regimes of neuronal activity. In particular, the model initially showed that it takes several seconds for astrocytes to buffer the majority of the potassium rapidly released by neurons in both basal and high regime of activity. Such model can also probe the selective contribution of ionic channels, and revealed for instance that disruption of the main astroglial potassium Kir4.1 channels not only favors the emergence of epileptiform activity, but also dysregulates neuronal excitability specifically during slow rhythmic activities. We here also extend the predictions of the model by assessing the selective contribution of the astroglial and neuronal Na/K ATPase, or volume of the extracellular space on potassium dynamics. We discuss these findings and their implications for neuronal information processing in the healthy and diseased brain.

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