Biology subjects

Scanziani, M.

Publications and source records attributed to Scanziani, M..

17 recordsLinked to original sources

bioRxiv2026

A cognitive representation in primary visual cortex modulated by vision

Primary visual cortex (V1) is a critical substrate for mammalian vision. Traditionally, visual inputs are thought to be the main drivers of V1 activity, with internal signals playing a modulatory role. Here we show that this relationship is inverted for a large fraction of V1 neurons. In rats completing a navigation task in darkness, these neurons encoded progress along physically distinct paths with a shared turn structure. Under illumination, visual stimuli gain-modulated this path-invariant activity rather than replacing it with stimulus-driven responses. Path-invariant V1 neurons were also preferentially coordinated with hippocampal ensembles during sharp-wave ripples, linking them to a brain-wide network involved in learning. These findings establish that an internal model of the world can serve as a primary driver of activity in sensory cortex.

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bioRxiv2026

Directional alignment of turn-related activity with locomotor dynamics in the superior colliculus

Fluid behavior requires temporal coordination across brain systems that orchestrate movement. A clear example is locomotion, in which left and right turns are not only precisely coordinated with the ongoing stepping rhythm but occur at opposite phases of the stepping cycle. The circuits underlying this coordination remain poorly understood. We discover that neuronal activity in the mouse superior colliculus, a conserved midbrain structure involved in turning behavior, is tightly phase-locked to the stepping rhythm. Notably, neurons selective for left and right turns fire at opposite phases of the stepping cycle. Moreover, this phase opposition is already evident during straight locomotion, before the animal initiates a turn. By aligning the activity of left and right turn neurons to opposite phases of the stepping cycle, the superior colliculus may create alternating windows of opportunity for left and right turns, facilitating the seamless execution of turns during locomotion.

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bioRxiv2026

Coordination of turn-related activity in the superior colliculus with locomotor dynamics and hippocampal representations of possible futures

The ability to represent possible futures allows animals to evaluate different options and act accordingly. The hippocampus can express representations of possible future paths, but the brain structures involved in transforming these representations into actions remain unknown. Here we show that hippocampal representations of possible future paths predict motor-related activity in the superior colliculus (SC), a midbrain structure involved in turning. By recording simultaneously from hippocampal neurons and from left- or right-preferring "turn cells" in the motor layers of the SC in navigating mice, we found that hippocampal representations of possible left or right future paths predicted increased firing rates of SC turn cells with matching left or right turn preference. This relationship was also evident in the animals' behavior: when the hippocampus represented future paths that were not ultimately taken, movement trajectories were nonetheless biased toward those paths, as if animals partially enacted possible futures that were represented but not selected. These results reveal a coordination between a cognitive and a motor structure and provide a potential pathway for mental simulations of possible futures to influence actions.

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bioRxiv2026

The Logic of Thalamic Inputs onto the Molecular Taxonomy of Cortical Neurons Reveals a Visual Hierarchy

The hierarchical organization of sensory cortices and the rich molecular taxonomy of their cell types are defining features of the mammalian cortex. Cortical areas along this hierarchy are reciprocally connected via the thalamus through bottom-up and top-down projections. The logic through which these projections map onto the cellular taxonomy of the cortex is, however, poorly understood. Here we combine an anterograde transsynaptic tracer with spatial transcriptomics to reveal the molecular and spatial identity of mouse visual cortical neurons downstream of thalamic starter neurons across visual cortical areas. Distinct thalamic inputs target characteristic sets of molecularly defined cortical neurons, forming bottom-up or top-down "signatures" defined by cell-type composition and the ratio of GABAergic to glutamatergic neurons. These signatures reveal a hierarchy spanning thalamic nuclei and visual cortical areas, independently predicted by the molecular and cellular similarities between cortical areas. This work uncovers basic principles of how bottom-up and top-down thalamic inputs map onto the cellular taxonomy in the visual cortex and establishes a cellular framework for the cortical hierarchy.

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bioRxiv2026

Vision shapes neural maps of space through an ancient midbrain pathway

Mammals rely on their senses to establish their position in space. Neural activity in the hippocampus maps position, yet how sensory signals reach the hippocampus remains poorly understood. Here we uncover the visual pathways informing spatial maps in the mouse hippocampus. Hippocampal activity in mice traversing a track in alternating periods of light and darkness revealed two distinct maps, one in light and one in dark. Surprisingly, distinct maps persisted following bilateral ablations of primary visual cortex, indicating that visual signals still reach the hippocampus. Conversely, blocking the ancestral pathway linking superior colliculus to lateral visual cortex markedly reduced the difference between light and dark maps. Thus, this conserved pathway relays visual information to the hippocampus, potentially explaining residual visual navigation in cortically blind humans.

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bioRxiv2026

Novel visuomotor adaptation paradigm reveals a role of visual cortex in the plasticity of innate behaviors in mice

A long-standing hypothesis in sensory neuroscience suggests that the evolutionary expansion of cortex in mammals may contribute to sensory-dependent adaptation by acting on subcortical pathways that drive innate behavior. However, direct experimental evidence is lacking. Taking the visual system as a model, it is known that there is significant interaction between the evolutionarily conserved Superior Colliculus (SC) and the comparatively modern Visual Cortex (VC), key structures in the mammalian visual system. In the SC, local alignment is established between a retinotopic map of the visual field and a map of orienting movement vectors during development and drives accurate visually guided orienting behavior throughout an organisms lifespan. Interestingly mammals, like humans and non-human primates, readily adapt to altered visual experiences, while evolutionarily older vertebrates, like amphibians, lack this behavioral plasticity. To address this outstanding question, we have developed a novel behavioral paradigm for inducing visuomotor adaptation in freely moving mice that is analogous to paradigms utilized in primates. Our paradigm combines a visually guided orienting task and a novel mouse prism goggle system to shift the visual field. Using this paradigm, we demonstrate for the first time that mice gradually adapt to a chronic shift of their full visual field, suggesting this type of behavioral plasticity is conserved across mammalian species. Furthermore, we show that lesioning primary visual cortex (V1) prior to shifting the visual field disrupts normal visuomotor adaptation, suggesting that VC may play a generative role in the plasticity of fundamental visually guided behaviors. These findings lend support to the hypothesis that a particular evolutionary benefit of sensory cortex is the allowance for experience-dependent behavioral plasticity.

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bioRxiv2024

Inter- and Intrahemispheric Sources of Vestibular Signals to V1

Head movements are sensed by the vestibular organs. Unlike classical senses, signals from vestibular organs are not conveyed to a dedicated cortical area but are broadcast throughout the cortex. Surprisingly, the routes taken by vestibular signals to reach the cortex are still largely uncharted. Here we show that the primary visual cortex (V1) receives real-time head movement signals -- direction, velocity, and acceleration -- from the ipsilateral pulvinar and contralateral visual cortex. The ipsilateral pulvinar provides the main head movement signal, with a bias toward contraversive movements (e.g. clockwise movements in left V1). Conversely, the contralateral visual cortex provides head movement signals during ipsiversive movements. Crucially, head movement variables encoded in V1 are already encoded in the pulvinar, suggesting that those variables are computed subcortically. Thus, the convergence of inter- and intrahemispheric signals endows V1 with a rich representation of the animals head movements.

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bioRxiv2024

The brain simulates actions and their consequences during REM sleep

Vivid dreams mostly occur during a phase of sleep called REM1-5. During REM sleep, the brains internal representation of direction keeps shifting like that of an awake animal moving through its environment6-8. What causes these shifts, given the immobility of the sleeping animal? Here we show that the superior colliculus of the mouse, a motor command center involved in orienting movements9-15, issues motor commands during REM sleep, e.g. turn left, that are similar to those issued in the awake behaving animal. Strikingly, these motor commands, despite not being executed, shift the internal representation of direction as if the animal had turned. Thus, during REM sleep, the brain simulates actions by issuing motor commands that, while not executed, have consequences as if they had been. This study suggests that the sleeping brain, while disengaged from the external world, uses its internal model of the world to simulate interactions with it.

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bioRxiv2022

Unifying model for three forms of contextual modulation including feedback input from higher visual areas

Sensory systems must combine local features with context to infer meaning. Accordingly, context profoundly influences neural responses. We developed a unified circuit model demonstrating how feedforward and feedback inputs are integrated to produce three forms of contextual effects in mouse primary visual cortex (V1). First, reanalyzing existing data, we discovered that increasing stimulus size only weakly increases the area of V1 neural response, conflicting with previous models of surround suppression (SS). Second, through modeling, we found that, in Layer 2/3, (1) SS and its contrast dependence are largely inherited from Layer 4; (2) Inverse responses (IR) - size-tuned responses to a gray "hole" in a full-field grating - are driven by feedback connections provided they are sufficiently wide; (3) Cross-orientation surround facilitation is induced by the summation of feedback input driving IR with the feedforward-driven classical center response. The model accounts for many previous findings and makes multiple testable predictions. HighlightsO_LIOne model explains three different types of contextual modulation C_LIO_LIThe widths of spatial response patterns grow much more slowly than stimulus size. C_LIO_LIInverse responses depend on the geometry of feedback response fields and projections C_LIO_LISummation of classical and inverse response accounts for surround facilitation. C_LI

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bioRxiv2021

Brain state-dependent modulation of thalamic visual processing by cortico-thalamic feedback

The behavioral state of a mammal impacts how the brain responds to visual stimuli as early as in the dorsolateral geniculate nucleus of the thalamus (dLGN), the primary relay of visual information to the cortex. A clear example of this is the markedly stronger response of dLGN neurons to higher temporal frequencies of the visual stimulus in alert as compared to quiescent animals. The dLGN receives strong feedback from the visual cortex, yet whether this feedback contributes to these state-dependent responses to visual stimuli is poorly understood. Here we show that in mice, silencing cortico-thalamic feedback abolishes state-dependent differences in the response of dLGN neurons to visual stimuli. This holds true for dLGN responses to both temporal and spatial features of the visual stimulus. These results reveal that the state-dependent shift of the response to visual stimuli in an early stage of visual processing depends on cortico-thalamic feedback.

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bioRxiv2021

Erasing motion: Scrambling direction selectivity in visual cortex during saccades

Distinguishing sensory stimuli caused by changes in the environment from those caused by an animals own actions is a hallmark of sensory processing. Saccades are rapid eye movements that shift the image on the retina. How visual systems differentiate motion of the image induced by saccades from actual motion in the environment is not fully understood. Here, we discovered that in mouse primary visual cortex (V1), the two types of motion evoke distinct activity patterns. This is because during saccades, V1 combines the visual input with a strong non-visual input arriving from the thalamic pulvinar nucleus. Thus, the pulvinar input ensures differential V1 responses to external and self-generated motion and may allow the animal to interpret sensory stimuli within the context of its actions.

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bioRxiv2020

A Disinhibitory Circuit for Contextual Modulation in Primary Visual Cortex

Context guides perception by influencing the saliency of sensory stimuli. Accordingly, in visual cortex, responses to a stimulus are modulated by context, the visual scene surrounding the stimulus. Responses are suppressed when stimulus and surround are similar but not when they differ. The mechanisms that remove suppression when stimulus and surround differ remain unclear. Here we use optical recordings, manipulations, and computational modelling to show that a disinhibitory circuit consisting of vasoactive-intestinal-peptide-expressing (VIP) and somatostatin-expressing (SOM) inhibitory neurons modulates responses in mouse visual cortex depending on the similarity between stimulus and surround. When the stimulus and the surround are similar, VIP neurons are inactive and SOM neurons suppress excitatory neurons. However, when the stimulus and the surround differ, VIP neurons are active, thereby inhibiting SOM neurons and relieving excitatory neurons from suppression. We have identified a canonical cortical disinhibitory circuit which contributes to contextual modulation and may regulate perceptual saliency.

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bioRxiv2020

Neurons in Visual Cortex are Driven by Feedback Projections when their Feedforward Sensory Input is Missing

We sense our environment through pathways linking sensory organs to the brain. In the visual system, these feedforward pathways define the classical feedforward receptive field (ffRF), the area in space where visual stimuli excite a neuron1. The visual system also uses visual context, the visual scene surrounding a stimulus, to predict the content of the stimulus2, and accordingly, neurons have been found that are excited by stimuli outside their ffRF3-8. The mechanisms generating excitation to stimuli outside the ffRF are, however, unclear. Here we show that feedback projections onto excitatory neurons in mouse primary visual cortex (V1) generate a second receptive field driven by stimuli outside the ffRF. Stimulating this feedback receptive field (fbRF) elicits slow and delayed responses compared to ffRF stimulation. These responses are preferentially reduced by anesthesia and, importantly, by silencing higher visual areas (HVAs). Feedback inputs from HVAs have scattered receptive fields relative to their putative V1 targets enabling the generation of the fbRF. Neurons with fbRFs are located in cortical layers receiving strong feedback projections and are absent in the main input layer, consistent with a laminar processing hierarchy. The fbRF and the ffRF are mutually antagonistic since large, uniform stimuli, covering both, suppress responses. While somatostatin-expressing inhibitory neurons are driven by these large stimuli, parvalbumin and vasoactive-intestinal-peptide-expressing inhibitory neurons have antagonistic fbRF and ffRF, similar to excitatory neurons. Therefore, feedback projections may enable neurons to use context to predict information missing from the ffRF and to report differences in stimulus features across visual space, regardless if excitation occurs inside or outside the ffRF. We have identified a fbRF which, by complementing the ffRF, may contribute to predictive processing.

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bioRxiv2020

Head Movements Control the Activity of Primary Visual Cortex in a Luminance Dependent Manner

The vestibular system broadcasts head-movement related signals to sensory areas throughout the brain, including visual cortex. These signals are crucial for the brains ability to assess whether motion of the visual scene results from the animals head-movements. How head-movements impact visual cortical circuits remains, however, poorly understood. Here, we discover that ambient luminance profoundly transforms how mouse primary visual cortex (V1) processes head-movements. While in darkness, head movements result in an overall suppression of neuronal activity, in ambient light the same head movements trigger excitation across all cortical layers. This light-dependent switch in how V1 processes head-movements is controlled by somatostatin expressing (SOM) inhibitory neurons, which are excited by head movements in dark but not in light. This study thus reveals a light-dependent switch in the response of V1 to head-movements and identifies a circuit in which SOM cells are key integrators of vestibular and luminance signals.

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bioRxiv2018

Visual physiology of the Layer 4 cortical circuit in silico

Despite advances in experimental techniques and accumulation of large datasets concerning the composition and properties of the cortex, quantitative modeling of cortical circuits under in-vivo-like conditions remains challenging. Here we report and publicly release a biophysically detailed circuit model of layer 4 in the mouse primary visual cortex, receiving thalamo-cortical visual inputs. The 45,000-neuron model was subjected to a battery of visual stimuli, and results were compared to published work and new in vivo experiments. Simulations reproduced a variety of observations, including effects of optogenetic perturbations. Critical to the agreement between responses in silico and in vivo were the rules of functional synaptic connectivity between neurons. Interestingly, after extreme simplification the model still performed satisfactorily on many measurements, although quantitative agreement with experiments suffered. These results emphasize the importance of functional rules of cortical wiring and enable a next generation of data-driven models of in vivo neural activity and computations.\n\nAUTHOR SUMMARYHow can we capture the incredible complexity of brain circuits in quantitative models, and what can such models teach us about mechanisms underlying brain activity? To answer these questions, we set out to build extensive, bio-realistic models of brain circuitry employing systematic datasets on brain structure and function. Here we report the first modeling results of this project, focusing on the layer 4 of the primary visual cortex (V1) of the mouse. Our simulations reproduced a variety of experimental observations in a large battery of visual stimuli. The results elucidated circuit mechanisms determining patters of neuronal activity in layer 4 - in particular, the roles of feedforward thalamic inputs and specific patterns of intracortical connectivity in producing tuning of neuronal responses to the orientation of motion. Simplification of neuronal models led to specific deficiencies in reproducing experimental data, giving insights into how biological details contribute to various aspects of brain activity. To enable future development of more sophisticated models, we make the software code, the model, and simulation results publicly available.

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bioRxiv2018

First spikes in visual cortex enable perceptual discrimination

Visually guided perceptual decisions involve the sequential activation of a hierarchy of cortical areas. It has been hypothesized that a brief time window of activity in each area is sufficient to enable the decision but direct measurements of this time window are lacking. To address this question, we develop a visual discrimination task in mice that depends on visual cortex and in which we precisely control the time window of visual cortical activity as the animal performs the task at different levels of difficulty. We show that threshold duration of activity in visual cortex enabling perceptual discrimination is between 40 and 80 milliseconds. During this time window the vast majority of neurons discriminating the stimulus fire one or no spikes and less than 16% fire more than two. This result establishes that the firing of the first visually evoked spikes in visual cortex is sufficient to enable a perceptual decision.

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bioRxiv2018

Emergence of Direction Selectivity at the Convergence of Thalamo-Cortical Synapses in Visual Cortex

Detecting the direction of an objects motion is essential for our representation of the visual environment. Visual cortex is one of the main stages in the mammalian nervous system where motion direction may be computed de novo. Experiments and theories indicate that cortical neurons respond selectively to motion direction by combining inputs that provide information about distinct spatial locations with distinct time-delays. Despite the importance of this spatiotemporal offset for direction selectivity its origin and cellular mechanisms are not fully understood. We show that ~80+/-10 thalamic neurons responding with distinct time-courses to stimuli in distinct locations contribute to the excitation of mouse visual cortical neurons during visual stimulation. Integration of thalamic inputs with the appropriate spatiotemporal offset provides cortical neurons with the primordial bias for direction selectivity. These data show how cortical neurons selectively combine the spatiotemporal response diversity of thalamic neurons to extract fundamental features of the visual world.

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