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Bonin, V.

Publications and source records attributed to Bonin, V..

13 recordsLinked to original sources

Cooperative processing of visual threat across collicular pathways

Rapid defensive actions require the transformation of sensory cues into appropriate motor responses. The superior colliculus is central to this transformation, containing defined cell-types that form parallel output pathways linking visual inputs to distinct behaviors. However, whether these pathways act independently or cooperate remains unclear. Here we combine cell-type-specific inhibition, large-scale electrophysiology, and functional ultrasound imaging to determine how these pathways contribute to visually evoked defensive behaviors. Inhibiting either narrow-field or wide-field neurons impaired escape to overhead visual threats, demonstrating that both pathways contribute to escape. Recordings from downstream targets revealed a compact representation in the deeper layers of the superior colliculus that selectively distinguished visual stimuli associated with escape, whereas the lateral posterior thalamus contained a broader representation of visual stimuli. The representation of visual threat in the deeper layers of the superior colliculus predicted escape initiation and vigor in freely moving animals. Across the brain, functional ultrasound imaging showed that visual stimuli recruited distinct patterns of activity that could not be explained by response magnitude alone or by the contribution of single cell-types. Together, these results reveal a cooperative circuit architecture in which parallel pathways carry distinct but complementary signals that jointly support visually evoked escape.

neuroscience↗

High-throughput serial two-photon tomography with BakingTray and BrainSaw

Volumetric imaging is increasingly important in fields such as neuroscience, where quantifying structure and mapping features are inherently three-dimensional problems. Block-face serial two-photon tomography (STPT) has emerged as a powerful approach for high-resolution, whole-organ volumetric imaging. STPT avoids complex sample preparation and balances image quality, speed, and scalability. However, STPT remains niche, in part because of the absence of flexible, general-purpose control software. Here we present BakingTray, an open-source software platform for STPT that extends ScanImage. BakingTrays modular framework accommodates diverse hardware configurations and allows users to build systems customised to their needs. Twelve such systems, which we call BrainSaws, have been constructed worldwide since 2016, with more under construction, and have so far contributed to 35 research papers. The three systems at the Sainsbury Wellcome Centre alone have acquired over 7,000 samples in a busy multi-user facility. We demonstrate the platform across its core neuroscience applications: electrode track localisation, brain-wide cell counting, and bulk projection mapping. Beyond these, we map the cell-type-specific synaptic output of inhibitory neurons in the ventral lateral geniculate nucleus and, with whole-mount staining, amyloid plaques brain-wide in a mouse model of Alzheimers disease. BakingTray is a mature platform for groups or facilities needing a customised volumetric imaging solution, whether built new or converted cheaply from an existing two-photon microscope.

neuroscience↗

Specific anterior-posterior brain-wide input patterns support specialized visuospatial processing in the mouse retrosplenial cortex

The retrosplenial cortex (RSC) is a key integrative hub involved in spatial orientation, navigation, and cognitive processes. In rodents, RSC neurons carry rich sensory and navigational signals and are interconnected with sensory, motor, thalamic, and hippocampal circuits--supporting multimodal integration. However, the circuitry that supports this integration remain unclear. Here, we combined 2-photon calcium imaging in navigating mice with brain-wide retrograde tracing to investigate how visual and positional information are represented and distributed across RSC subregions. We found a clear anterior-posterior gradient: anterior RSC neurons exhibited sharper, more reliable position tuning and preferred fast-moving visual stimuli, while posterior RSC neurons showed broader tuning and preferential responses to slower motion. These functional differences were paralleled by distinct patterns of long-range input: anterior RSC received denser projections from motor, parietal, and hippocampal-associated areas--regions implicated in position encoding--whereas posterior RSC was more strongly innervated by visual cortices. Our findings reveal that the RSC contains functionally and anatomically distinct subregions specialized for processing different visuospatial features, suggesting a modular organization that supports integration of contextual and sensory information during navigation.

neuroscience↗

Intracortical bipolar stimulation allows selective activation of neuronal populations in the cortex

BackgroundIntracortical electrical stimulation has emerged as a promising approach for sensory restoration, such as a cortical visual prosthesis, yet its effectiveness is limited by current spread and electrode density constraints. ObjectiveTo determine whether intracortical bipolar current steering--via modulation of the return electrode position--can enhance neural activation selectivity compared to traditional monopolar stimulation, with the aim of improving spatial precision in sensory restoration. MethodsWe applied intracortical stimulation and used two-photon calcium imaging on acute brain slices to directly visualize neural responses to bipolar stimulation. Biophysical computational modeling was used to complement the experimental results. The analysis included both cellular and population-level assessments to evaluate the impact of several stimulation patterns, such as current direction, electrode spacing and current amplitude, on recruitment patterns. ResultsBipolar stimulation selectively activated distinct neural populations based on the direction of the current flow. This approach decreased the overlap between activated groups and increased the number of independently addressable neural clusters by up to 9-fold relative to monopolar stimulation. Moreover, the electrode configuration and spacing critically influenced the spatial spread of activation. ConclusionsIntracortical bipolar current steering enhances neural activation selectivity by engaging independent neural populations through current directionality. These findings suggest that this strategy may improve the spatial precision of neural prosthetics and sensory restoration without the need for an increased electrode density.

neuroscience↗

Dendritic Architecture Enables de Novo Computation of Salient Motion in the Superior Colliculus

Dendritic architecture plays a crucial role in shaping how neurons extract behaviorally relevant information from sensory inputs. Wide-field neurons in the superior colliculus integrate visual information from the retina to encode cues critical for visually guided orienting behaviors. However, the principles governing how these neurons filter their inputs to generate appropriate responses remain unclear. Using viral tracing, two-photon calcium imaging, and computational modeling, we show that wide-field neurons receive functionally diverse inputs from twelve retinal ganglion cell types, forming a layered, type-specific organization along their dendrites. This structured arrangement allows wide-field neurons to multiplex salient motion cues, selectively amplifying movement and suppressing static features. Computational models reveal that the spatial organization of dendrites and inputs enables the selective extraction of behaviorally relevant stimuli, including de novo computations. Our findings underscore the critical role of dendritic architecture in shaping sensory processing and neural circuit function.

neuroscience↗

Distinct functional roles and connectivity rules for lower- and higher-order intracortical and pulvinar thalamocortical pathways in mouse visual cortex

Functional specialization of cortical areas is a fundamental feature of brain organization and is critical for perception and behavior. Such an organization must depend on specialized connectivity between areas, yet the underlying wiring rules remain unclear. We characterized intracortical and thalamocortical pathways in the mouse visual cortex using neural tracing and functional imaging. We uncovered multiple structural-functional connectivity rules underlying the functional specialization of higher visual cortical areas (HVAs). Individual higher visual areas integrate specific cortical and thalamic inputs with distinct functional biases. Higher order Layer 2/3 and thalamocortical pathways show higher target specificity than feedforward intracortical pathways and might impart specific functional preferences to the recipient HVAs. In contrast, higher order Layer 5 pathways lacking specificity may contribute to the tuning diversity in the recipient HVAs. Altogether, this study reveals fundamental organization rules of long-range interareal connectivity that underlie the parallel modular organization of the visual cortex. HIGHLIGHTSO_LIHVAs AL, PM and A receive diverse and specific inputs from V1, HVA and LP pathways C_LIO_LIDensity of intracortical inputs correlates with similarity of tuning between visual areas C_LIO_LITuning of HVA inputs correlates with HVAs preferences and functional heterogeneity C_LIO_LIHVA output pathways differ in tuning homogeneity and target specificity C_LI

neuroscience↗

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's Disease

Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimers disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex, several years before amyloid deposition. We found the same early cingulate FC disruption and neuronal hyperactivity in AppNL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astroglial calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral hyperactivity. In conclusion, we show for the first time that astrocytes mediate initial features of AD and drive clinically relevant phenotypes.

neuroscience↗

Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits.

How neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here we investigate human cortical neuron development, plasticity and function, using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, and in vivo structural and functional imaging revealed that the human neurons develop morphologically and functionally following a prolonged developmental timeline, revealing the cell-intrinsic retention of juvenile properties of cortical neurons as an important mechanism underlying human brain neoteny. Following maturation, human neurons transplanted in the visual cortex display tuned responses to visual stimuli that are similar to those of mouse neurons, indicating capacity for physiological synaptic integration of human neurons in mouse cortical circuits. These findings provide new insights into human neuronal development, and open novel experimental avenues for the study of human neuronal function and diseases.\n\nHighlightsO_LICoordinated morphological and functional maturation of ESC-derived human cortical neurons transplanted in the mouse cortex.\nC_LIO_LITransplanted neurons display prolonged juvenile features indicative of intrinsic species-specific neoteny.\nC_LIO_LITransplanted neurons develop elaborate dendritic arbors, stable spine patterns and long-term synaptic plasticity.\nC_LIO_LIIn the visual cortex transplanted neurons display tuned visual responses that resemble those of the host cortical neurons.\nC_LI

neuroscience↗

Segregated encoding of spatiotemporal features in the mouse visual cortex

Visual processing and behavior depend on specialized neural representations and information channels that encode distinct visual information and enable distinct computations. Our understanding of the neural substrate, however, remain severely limited by sparse recordings and the restricted range of visual areas and visual stimuli considered. We characterized in the mouse the multidimensional spatiotemporal tuning properties of > 30,000 layer 2/3 pyramidal neurons across seven areas of the cortex. The dataset reveals population specialized for processing of oriented and non-oriented contrast, spatiotemporal frequency, and motion speed. Areal analysis reveals profound functional diversity and specificity as well as highly specific representations of visual processing channels in distinct visual areas. Clustering analysis shows a branching of visual representations along the posterior to anterior axis, and between lateral and dorsal areas. Overall, this dataset provides a cellular-resolution atlas for understanding organizing principles underlying sensory representations across the cortex. SummaryVisual representations and visual channels are the cornerstones of mammalian visual processing and critical for a range of life sustaining behaviors. However, the lack of data sets spanning multiple visual areas preclude unambiguous identification of visual processing streams and the sparse, singular recording data sets obtained thus far are insufficient to reveal the functional diversity of visual areas and to study visual information channels. We characterized the tunings of over 30,000 cortical excitatory neurons from 7 visual areas to a broad array of stimuli and studied their responses in terms of their ability to encode orientation, spatiotemporal contrast and visual motion speed. We found all mouse visual cortical areas convey diverse information but show distinct biases in terms of numbers of neurons tuned to particular spatiotemporal features. Neurons in visual areas differ in their spatiotemporal tuning but also in their relative response to oriented and unoriented contrast. We uncovered a population that preferentially responds to unoriented contrast and shows only weak responses to oriented stimuli. This population is strongly overrepresented in certain areas (V1, LM and LI) and underrepresented in others (AL, RL, AM, and PM). Spatiotemporal tunings are broadly distributed in all visual areas indicating that all areas have access to broad spatiotemporal information. However, individual areas show specific biases. While V1 is heavily biased in favor of low spatial and temporal frequencies, area LM responds more strongly to mid-range frequencies. Areas PM and LI are biased in favor of slowly-varying high-resolution signals. By comparison, anterior areas AL, RL and AM are heavily biased in favor of fast-varying, low to mid spatial frequency signals. Critically, theses biases express themselves in vastly different number of cells tuned to particular features, suggesting differential sampling of visual processing channels across areas. Comparing across areas, we found divergent visual representations between anterior and posterior areas, and between lateral and dorsal areas, suggesting the segregated organization of cortical streams for distinct information processing.

neuroscience↗

Characterizing the nonlinear structure of shared variability in cortical neuron populations using neural networks

Sensory neurons often have variable responses to repeated presentations of the same stimulus, which can significantly degrade the information contained in those responses. Such variability is often shared across many neurons, which in principle can allow a decoder to mitigate the effects of such noise, depending on the structure of the shared variability and its relationship to sensory encoding at the population level. Latent variable models offer an approach for characterizing the structure of this shared variability in neural population recordings, although they have thus far typically been used under restrictive mathematical assumptions, such as assuming linear transformations between the latent variables and neural activity. Here we leverage recent advances in machine learning to introduce two nonlinear latent variable models for analyzing large-scale neural recordings. We first present a general nonlinear latent variable model that is agnostic to the stimulus tuning properties of the individual neurons, and is hence well suited for exploring neural populations whose tuning properties are not well characterized. This motivates a second class of model, the Generalized Affine Model, which simultaneously determines each neurons stimulus selectivity and a set of latent variables that modulate these stimulus responses both additively and multiplicatively. While these approaches can detect general nonlinear relationships in shared neural variability, we find that neural activity recorded in anesthetized primary visual cortex (V1) is best described by a single additive and single multiplicative latent variable, i.e., an \"affine model\". In contrast, application of the same models to recordings in awake macaque prefrontal cortex discover more general nonlinearities to compactly describe the population response variability. These results thus demonstrate how nonlinear latent variable models can be used to describe population variability, and suggest that a range of methods is necessary to study different brain regions under different experimental conditions.

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Behavioral response to visual motion impacts population coding in the mouse visual thalamus

Visual motion is a ubiquitous component of animals sensory experience and its encoding is critical for navigation and movement. Yet its impact on behavior and neural coding is not well understood. Combining pupillometry with cellular calcium imaging measurements of thalamocortical axons in awake behaving mice, we examined the impact of arousal and behavioral state on encoding of visual motion in the visual thalamus. We discovered that back-to-front visual motions elicits a robust behavioral response that shapes tunings of visual thalamic responses. Consistent with an arousal mechanism, the effects were pronounced during stillness and weak or absent during locomotor activity and under anesthesia. The impact on neuronal tuning was specific, biasing population response patterns in favor of back-to-front motion. The potent influence of visual motion on behavioral state dynamically affect sensory coding at early visual processing stages. Further research is required to reveal the circuitry and function of this novel mechanism.

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Astrocytes integrate local sensory and brain-wide neuromodulatory signals.

Astrocytes play multiple functions in the central nervous system, from control of blood flow through to modulation of synaptic activity. Transient increases in intracellular Ca2+ are thought to control these activities. The prevailing concept is that these Ca2+ transients are triggered by distinct pathways, with little mechanistic and functional overlap. Here we demonstrate that astrocytes in visual cortex of mice encode local visual signals in conjunction with arousal state, functioning as multi-modal integrators. Such activity adds an additional layer of complexity to astrocyte function and may enable astrocytes to specifically and subtly regulate local network activity and plasticity.

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Encoding of Tactile Context in the Mouse Visual Cortex

Multisensory integration is key for perception and animal survival yet how information from separate senses is integrated has been debated for decades. In the cortex, information from each sense is first processed in primary sensory areas and then combined in association areas. An alternative hypothesis to this hierarchical model is that primary sensory cortices partake in multisensory encoding. We probed tactile and visual responses in primary somatosensory and visual cortices in awake behaving animals using two-photon calcium imaging from layer 2/3 excitatory neurons. In support of an hierarchical model we found segregation of visual and tactile responses. Tactile stimuli evoked responses in S1 neurons. In striking contrast, V1 neurons failed to respond to tactile stimuli. This was true for passive whisker stimulation and for stimulation during active whisking. Furthermore, responses of V1 neurons to congruent visuo-tactile cues during active exploration, a condition where vision precedes touch, were completely abolished in darkness. The rostro-lateral area of the visual cortex responded to both visual and tactile aspects of the stimuli and may form a substrate for encoding multisensory signals during active exploration. Our results indicate that primary sensory areas mainly encode their primary sense and that the impact of other modalities may be restricted to modulatory effects.

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