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Storchi, R.

Publications and source records attributed to Storchi, R..

13 recordsLinked to original sources

Parallel visual processing in the suprachiasmatic region of a diurnal mammal.

Light shapes mammalian physiology and behaviour through hypothalamic pathways, yet how these pathways process visual information in day-active species remains poorly understood. Based largely on work in nocturnal rodents, the suprachiasmatic nucleus (SCN) is classically viewed as a retinal target that encodes ambient illumination for circadian entrainment. We combine anatomical tracing, light-evoked c-Fos mapping and high-density silicon-probe electrophysiology to define visual processing in the suprachiasmatic region of the diurnal murid Rhabdomys pumilio. We find that retinal input and light-evoked activity extend beyond the SCN into rostral and lateral peri-SCN hypothalamus. Within the SCN, neurons encode irradiance with graded changes in maintained firing broadly similar to those observed in parallel recordings of nocturnal Mus domesticus. Across the wider suprachiasmatic region, Rhabdomys neurons show selectivity for more dynamic visual stimuli, including luminance transitions, contrast and temporal structure. Unsupervised clustering identifies five functionally distinct hypothalamic visual response classes with different anatomical distributions. These findings reveal an expanded hypothalamic visual network in a diurnal mammal, placing SCN irradiance coding within a broader system for processing dynamic visual features.

neuroscience↗

Circadian phase reconfigures information transmission in the mouse visual thalamus

Circadian clocks are a ubiquitous feature of the mammalian brain, yet whether they regulate how neural circuits encode and transmit information remains largely unknown. Here, we address this question in the mouse visual thalamus (dLGN), a key relay between retina and cortex that provides a tractable model for studying sensory information transfer. Using wireless electrophysiological recordings from awake, behaving mice, we show that spontaneous dLGN activity is under circadian control, peaking during the late subjective day. Combining visual stimulation, information-theoretic analyses, and optogenetic interrogation of retinogeniculate transmission, we demonstrate that circadian phase selectively reconfigures the visual code. Although fundamental tuning properties remain largely stable, the impact of circadian phase on information transfer depends on visual scene statistics, promoting a more efficient coding strategy at night under high-contrast conditions. Together, these findings identify circadian clocks as dynamic regulators of neuronal communication that actively reshape sensory information processing across the day-night cycle.

neuroscience↗

A system for 3D reconstruction of mouse behaviour

Recent development in machine vision has enabled researchers unprecedented resolution in measuring behaviour in freely moving animals. However, the hardware implementation of a behavioural arena for capturing 3D behaviours remains time consuming and unstandardised. Here we first provide detailed instructions on how to build and calibrate such a system. Secondly, we provide instructions on how to process video data to obtain a 3D reconstruction of mouse behaviour. Finally, we provide results from behavioural tests in which 3D reconstruction enables clear-cut separation of behavioural responses to distinct sensory stimuli. Data and Software AvailabilityAll data and analyses software required for this article is provided in a publicly available repository [1] Competing InterestsThis project contains the following underlying data. Grant InformationThis work was funded by NC3Rs via a David Sainsbury Fellowship (Project Reference NC/P001505/1).

neuroscience↗

Efficient mixed representation of active and passive motion in the mouse visual thalamus during natural behaviour

Most retinal motion is generated by the observer's movements. These are often self-generated (active) but can also arise from external forces such as gravity (passive). Active movements modulate spontaneous and visually evoked activity throughout the visual system, providing neural circuits with information about behavioural state. By contrast, much less is known about how visual circuits represent passive movements. Critically, it remains unclear whether the retina-recipient thalamus tracks passive motion and, if so, whether this representation is separable from active motion. To address these questions, we developed a paradigm that dissociates active and passive motion in freely moving mice and used it to examine their effects on neural activity. Mice actively explored an arena while intermittent floor tilts induced passive movement. By combining 3D reconstructions of animal pose and arena motion, we quantified active and passive linear and angular motion independently, even when they occurred simultaneously. We found that neurons in the dorsal lateral geniculate nucleus (dLGN) and surrounding regions tracked combinations of active and passive motion signals both in the dark and during visual stimulation. Individual neurons differentially weighted active and passive motion signals. This diversity enabled active and passive motion signals to be linearly decoded and partially separated from population activity, while recurrent dynamics retained passive motion information over timescales of several seconds. These findings identify a coding strategy through which early visual circuits integrate active and passive motion into an estimate of self-motion while preserving information about whether visual inputs arise from self-generated or externally imposed movements.

neuroscience↗

Embodied processing in whisker somatosensory cortex during exploratory behaviour in freely moving mice

Sensory systems have evolved to solve computational challenges that animals face during behaviour in their natural environments. To illuminate how sensory cortex operates under such conditions, we investigated the function of neurons in whisker-related Somatosensory Cortex (wS1) of freely moving mice, engaged in tactile exploratory behaviour. By recording neural activity from wS1 whilst tracking the mouse body in 3D, we found that wS1 neurons are substantially modulated by body state (configuration of individual body-parts and their derivatives), even in the absence of whisker afferent input. Most neurons were modulated by multiple dimensions of body state, with the most prominently encoded being the angle of the head to the body and locomotion speed. Overall, our data suggest that sensory cortex functions as an embodied representation, which integrates signals from its associated sense organ within a body schema.

neuroscience↗

Enhanced restoration of visual code after targeting on bipolar cells compared to retinal ganglion cells with optogenetic therapy

Optogenetic therapy is a promising vision restoration method where light sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence the quality of restored vision. However, a like-for-like pre-clinical comparison of visual responses evoked following equivalent opsin expression in the two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), is absent. We address this deficit by comparing stimulus-response characteristics at single unit resolution in retina and dorsal lateral geniculate nucleus (dLGN) of retinally degenerate mice genetically engineered to express the opsin ReaChR in Grm6- or Brn3c-expressing cells (ON BC vs RGCs respectively). For both targeting strategies, we find ReaChR-evoked responses have equivalent sensitivity and can encode contrast across different background irradiances. Compared to ON BCs, targeting RGCs decreased response reproducibility and resulted in more stereotyped responses with reduced diversity in response polarity, contrast sensitivity and temporal frequency tuning. Recording ReaChR-driven responses in visually intact retinas confirmed that RGC-targeted ReaChR expression disrupts visual feature selectivity of individual RGCs. Our data show that while both approaches restore visual responses with impressive fidelity, ON BC targeting produces a richer visual code better approaching that of wildtype mice.

neuroscience↗

Reconfiguration of the visual code and retinal cell type complement in closely related diurnal and nocturnal mice

How does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal cell composition in closely related murid species with different behaviours. Rhabdomys pumilio are diurnal and have substantially thicker inner retina and larger visual thalamus than nocturnal Mus musculus. High-density electrophysiological recordings of visual response features in the dorsal lateral geniculate nucleus (dLGN) reveals that Rhabdomys attains higher spatiotemporal acuity both by denser coverage of the visual scene and a selective expansion of elements of the code characterised by non-linear spatiotemporal summation. Comparative analysis of single cell transcriptomic cell atlases reveals that realignment of the visual code is associated with increased relative abundance of bipolar and ganglion cell types supporting OFF and ON-OFF responses. These findings demonstrate how changes in retinal cell complement can reconfigure the coding of visual information to match changes in visual needs.

neuroscience↗

Functional integrity of visual coding following advanced photoreceptor degeneration

Photoreceptor degeneration sufficient to produce severe visual loss often spares the inner retina. This raises the hope that treatments using optogenetics or electrical stimulation, which generate a replacement light input signal in surviving neurons, may restore vision. The success of these approaches is dependent on the capacity of surviving circuits in the early stages of the visual system to generate and propagate an appropriate visual code in the face of neuroanatomical remodelling. To determine the capacity of surviving circuits in advanced retinal degeneration to present an appropriate visual code, we generated a transgenic mouse expressing the optogenetic actuator ReaChR in ON bipolar cells (second order neurons in the visual projection). After crossing this with the rd1 model of photoreceptor degeneration, we compared ReaChR derived responses with photoreceptor-driven responses in wildtype (WT) mice in retinal ganglion cells and visual thalamus. The ReaChR-driven responses in rd1 animals showed low photosensitivity, but in other respects generated a visual code that was very similar to WT. Furthermore, ReaChR rd1 units in the retina had high response reproducibility and showed sensitivity normalisation to code contrast stably across different background intensities. At the single unit level, ReaChR-derived responses exhibited broadly similar variation in light response polarity, contrast sensitivity and temporal frequency tuning as WT. Units from WT and ReaChR rd1 mice clustered together when subjected to unsupervised community detection based on stimulus-response properties. Our data reveal an impressive ability for surviving circuitry to recreate a rich visual code following advanced retinal degeneration and are promising for regenerative medicine in the central nervous system.

neuroscience↗

Look-up and look-down neurons in the mouse visual thalamus during freely moving exploration

The traditional view that visuomotor integration is a property of higher brain centres has recently been challenged by the discovery in head-fixed rodents that locomotion increases neuronal activity throughout the early visual system (including the retina). Any appreciation of the importance of this behavioural modulation of visual inputs must encompass a comprehensive understanding of the range of behaviours engaged by this mechanism. This information is unavailable from head-fixed preparations in which head and body postures are fundamentally constrained and dissociated from their natural coupling with visual experience. We addressed this deficit by recording spiking activity from the primary visual thalamus during freely moving exploration, while simultaneously applying frame-by-frame quantification of postures and movements to robust 3D reconstructions of head and body. We found that postures associated with the animal looking up/down affected activity in >50% neurons. The extent of this effect was comparable to that induced by locomotion. Moreover, the two effects were largely independent and jointly modulated neuronal activity. Thus, while most units were excited by locomotion, some expressed highest firing when the animal was looking up ("look up" neurons) while others when the animal was looking down ("look-down" neurons). These results were observed in the dark, thus representing a genuine behavioural modulation, and were amplified in a lit arena. These findings define the influence of natural exploratory behaviour on activity in the early visual system and reveal the importance of up/down postures in gating neuronal activity in the primary visual thalamus.

neuroscience↗

Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons

There is no consensus on the best optogenetic tool for neuronal inhibition. Lamprey parapinopsin ( Lamplight) is a Gi/o-coupled bistable animal opsin that can be activated and deactivated by short and long wavelength light, respectively. Since native mechanisms of neuronal inhibition frequently employ Gi/o signalling, we asked here whether Lamplight could be used for optogenetic silencing. We show that short (405nm) and long (525nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, and that combining these wavelengths can be used to achieve intermediate levels of activity. We demonstrate that these properties can be applied to produce switchable and scalable neuronal hyperpolarisation, and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. We show that expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, and that 405 and 525nm stimuli can produce responses of opposite sign in output neurons of the retina. Lamplight-driven responses to both activating (405nm) and deactivating (525nm) light can occur within 500ms and be elicited by intensities at least 10x below threshold for available inhibitory optogenetic tools. We conclude that Lamplight can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and rapidly reversible.

neuroscience↗

Beyond locomotion: in the mouse the mapping between sensations and behaviours unfolds in a higher dimensional space

Instinctive defensive behaviours, consisting of stereotyped sequences of movements and postures, are an essential component of the mouse behavioural repertoire. Since defensive behaviours can be reliably triggered by threatening sensory stimuli, the selection of the most appropriate action depends on the stimulus property. However, since the mouse has a wide repertoire of motor actions, it is not clear which set of movements and postures represent the relevant action. So far this has been empirically identified as a change in locomotion state. However, the extent to which locomotion alone captures the diversity of defensive behaviours and their sensory specificity is unknown. To tackle this problem we developed a method to obtain a faithful 3D reconstruction of the mouse body that enabled to quantify a wide variety of motor actions. This higher dimensional description revealed that defensive behaviours are more stimulus-specific than indicated by locomotion data. Thus, responses to distinct stimuli that were equivalent in terms of locomotion (e.g. freezing induced by looming and sound) could be discriminated along other dimensions. The enhanced stimulus-specificity was explained by a surprising diversity. A clustering analysis revealed that distinct combinations of movements and postures, giving rise to at least 7 different behaviours, were required to account for stimulus-specificity. Moreover, each stimulus evoked more than one behaviour revealing a robust one-to-many mapping between sensations and behaviours that was not apparent from locomotion data. Our results indicate that diversity and sensory specificity of mouse defensive behaviours unfold in a higher dimensional space spanning multiple motor actions.

animal behavior and cognition↗

Infra-slow modulation of fast beta/gamma oscillations in the mouse visual system.

Infra-slow (<0.02 Hz) and fast beta/gamma (20 - 100 Hz) oscillations in neurophysiological activity have been widely found in the subcortical visual system. While it is well established that fast beta/gamma oscillations are involved in visual processing, the role (if any) of infra-slow oscillations is currently unknown. One possibility is that infra-slow oscillations exert influence by modulating the amplitude of fast oscillations, yet the extent to which these different oscillations arise independently and interact remains unknown. We addressed these questions by recording in vivo spontaneous activity from subcortical visual system of visually intact mice, and animals whose retinal network was disrupted by advanced rod/cone degeneration (rd/rd cl) or melanopsin loss (Opn4-/- We found many neurons expressing only one type of oscillation, and indeed fast oscillations were absent in rd/rd cl. Conversely, neurons co-expressing the two oscillations were also common, and were encountered more often than expected by chance in visually intact but not Opn4-/- mice. Finally, where they co-occurred we found that beta/gamma amplitude was modulated by the infra-slow rhythm. Our data thus reveal that: 1.) infra-slow and beta-gamma oscillations are separable phenomena; and 2.) that they actively co-occur in a subset of neurones in which the phase of infra-slow oscillations define beta-gamma oscillation amplitude. These findings suggest that infra-slow oscillations could influence vision by modulating beta-gamma oscillations, and raise the possibility that disruptions in these oscillatory behaviours contribute to vision dysfunction in retinal dystrophy. KEY POINTS SUMMARYO_LINeurophysiological activity in the subcortical visual system fluctuates in both infra-slow and fast oscillatory ranges, however the level of co-occurrence and potential functional interaction of these rhythms is unknown. C_LIO_LIAnalyzing dark-adapted spontaneous activity in the mouse subcortical visual system, we find that these two types of oscillation interact uniquely through a population of neurons expressing both rhythms. C_LIO_LIGenetic ablation of rod/cone signaling potentiates infra-slow and abolishes fast beta/gamma oscillations while genetic ablation of melanopsin substantially diminishes the interaction between these two rhythms. C_LIO_LIOur results indicate that in an intact visual system the phase of infra-slow modulates fast beta/gamma oscillations. C_LIO_LIThus one possible impact of infra-slow oscillations in vision is to guide visual processing by interacting with fast narrowband oscillations. C_LI

neuroscience↗

Measuring vision using innate behaviours in mice with intact and impairedretina function

Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests for perceptual vision, such as the visual water task, rely on learning. The learning process, while effective for sighted animals, can be laborious and stressful in animals with impaired vision, requiring long periods of training. Current tests that that do not require training are based on sub-conscious, reflex responses (e.g. optokinetic nystagmus) that dont require involvement of visual cortex and higher order thalamic nuclei. A potential alternative for measuring vision relies on using visually guided innate defensive responses, such as escape or freeze, that involve cortical and thalamic circuits. In this study we address this possibility in mice with intact and degenerate retinas. We first develop automatic methods to detect behavioural responses based on high dimensional tracking and changepoint detection of behavioural time series. Using those methods, we show that visually guided innate responses can be elicited using parametisable stimuli, and applied to describing the limits of visual acuity in healthy animals and discriminating degrees of visual dysfunction in mouse models of retinal degeneration.

neuroscience↗