Biology subjects

Niell, C. M.

Publications and source records attributed to Niell, C. M..

16 recordsLinked to original sources

bioRxiv2026

Temporally organized activity in mouse V1 encodes newly sampled visual content during free movement

Natural vision is continuously shaped by an animal's own movements, which determine what enters the visual system and when visual input changes. Gaze shifts are known to initiate a temporally structured sequence of activity in primary visual cortex (V1), but how the visual content sampled by each movement contributes to this sequence has remained unclear. We recorded visual input, eye and head movements, and V1 activity in freely moving mice, and asked how the visual content sampled on each gaze shift shapes the response. The magnitude of visual change induced by each gaze shift scaled the amplitude of responses according to each neuron's characteristic response profile, while movement amplitude alone did not reproduce this modulation in darkness, supporting a role of visual input in driving the sequence. Activity following gaze shifts reflected each neuron's spatial receptive field structure, and visual filters estimated under head-fixed conditions predicted the relative timing of spike responses during gaze shifts of freely moving animals, demonstrating that gaze shift responses encode visual information. At the population level, decoded V1 activity shifted toward the scene sampled after each gaze shift. Thus, across single-neuron, spatial, temporal, and population measures, V1 activity tracked the content of each sample beyond movement timing alone, indicating that gaze shifts act as sampling events that result in V1 encoding visual information in temporally ordered responses.

neuroscience↗

bioRxiv2026

Visual uncertainty and task demands shape active sensing strategies in mice

In natural environments, animals actively sample visual information to guide behavior. Sensory feedback is dynamic and often requires active movements, whether saccading across the lines of this page or walking through a park. From high-acuity vision in hawks to low-acuity mice, many animals actively navigate to seek information, which can be called infotaxis. Although mice have relatively low-acuity vision, they still rely on sight for critical behaviors including navigation and prey capture. Yet, how sensitive they are to visual information and performing infotaxis has not been established. Here, we develop a virtual reality object discrimination task to investigate visual decision-making under naturalistic conditions. We show that mice perform infotaxis by actively seeking out informative views to guide their choices. Stimulus manipulations confirm that this strategy is modulated by the amount of available visual information. These results reveal that mice use principled active strategies to resolve visual uncertainty, highlighting a key role for information-seeking in natural vision. HighlightsO_LIMice perform active visual sensing in a free-range VR object discrimination task. C_LIO_LIThey perform infotaxis and select the correct object under variable visibility. C_LIO_LIDecisions decoded from head-body movements and speed reflect occlusion sensitivity. C_LI

neuroscience↗

bioRxiv2026

Gaze shifts in freely moving mice comprise distinct head-eye coordination motifs

Freely moving mice are generally thought to redirect gaze mainly through head-coupled movements, with eye movements stabilizing the retinal image or resetting eye position. This reflexive view leaves unresolved whether gaze shifts also include active coordination modes. Here we show that a single gaze-shift class resolves into multiple distinct head-eye coordination motifs. Using high-resolution head and eye tracking in freely moving mice, we identified four reproducible motifs: Head-before-Eye (HbE), Head-with-Eye (HwE), Head-Dominant (HD), and Eye-Dominant (ED). The motifs differed in head-eye timing, locomotor context, and pre-onset visual-behavioral structure. Their short-timescale sequential organization was non-random: HD formed alternating side-to-side head movements, whereas HwE-HbE-ED formed a directed transition chain preserved within each movement direction. Simultaneous neural recordings further revealed motif-dependent responses in primary visual cortex (V1) and superficial superior colliculus (sSC), with stronger sSC than V1 modulation for the three motifs distinguished by pre-onset visual-behavioral structure (all but HbE). HwE showed the clearest signature of active orienting, combining near-synchronous head-eye onset, strong relevance to visual-behavioral features, and the largest pre-onset and earliest peri-onset responses in sSC. These results expand a unitary view of gaze shifts in freely moving mice into a diverse, structured repertoire of coordination motifs, and identify HwE as a candidate active gaze-shift mode during natural behavior.

animal behavior and cognition↗

bioRxiv2026

Vision guides directed orienting movements during obstacle avoidance in mice

In natural environments, animals must effectively maneuver around obstacles to reach goals such as food or shelter. Recent work has demonstrated that laboratory mice use vision for naturalistic behavior such as prey capture, escape, and distance estimation. However, it is unknown to what extent mice use vision relative to other senses such as touch for obstacle avoidance, a critical natural behavior. In this study we developed an obstacle avoidance task in freely moving mice to investigate how vision is used to guide paths around an obstacle obstructing a goal. We found that mice clearly use vision to avoid an obstacle, steering around the obstacle at distances where tactile information isnt available. By comparing trajectories for mice performing obstacle avoidance in the light versus the dark, we found that vision contributes to more spatially efficient trajectories and paths directed to the open edge of the obstacle. When vision is available, mice make large orienting movements towards the opening of the obstacle at about 10 cm from its edge, suggesting that mice are actively using visual information to direct these movements. Finally, by occluding one eye, we found that mice were still able to avoid obstacles with primarily monocular information. Taken together, these results demonstrate that laboratory mice use vision to avoid an obstacle, taking directed paths that are initiated by large orienting movements. In addition to demonstrating the visual behavioral capabilities of the mouse, this paradigm can serve as a foundation to study the neural circuits that mediate visually guided orienting and locomotion. HighlightsO_LIWe developed a simple obstacle avoidance task for freely moving mice that requires minimal training C_LIO_LIVision is necessary for efficient and directed paths around an obstacle C_LIO_LIMice steer around obstacles by performing directed head movements towards clear paths C_LIO_LIMice do not require binocular vision for obstacle avoidance C_LI

neuroscience↗

bioRxiv2025

The impact of the serotonergic psychedelic DOI on active vision in freely moving mice

Psychedelics offer a unique opportunity to investigate the neural mechanisms governing both normal and altered perceptual states, yet relatively little is known about their impact on visual processing at the level of neural coding, particularly in the context of active vision. Here we examined how the serotonergic psychedelic DOI (2,5-dimethoxy-4-iodoamphetamine) influences neural activity within the visual cortex (V1) of freely moving mice engaged in naturalistic vision. Previous work has demonstrated that, under normal conditions, gaze shifts trigger a temporal sequence in V1 that encodes visual information in a coarse-to-fine sequence. Here we found that DOI had a diverse and temporally dynamic impact on response amplitudes across this sequence -- while net population-level firing was modestly suppressed, individual neurons showed large increases or decreases in their gaze shift responses. Strikingly, this bidirectional modulation was correlated with gaze-shift response latency. DOI had mixed effects on short latency, low spatial frequency preferring neurons, but became increasingly suppressive across the sequence, ultimately suppressing nearly all long latency, high spatial frequency preferring neurons. These findings demonstrate how psychedelics disrupt naturalistic visual processing and support a framework in which visual hallucinations result from an imbalance in coarse and fine input integration during active vision. HighlightsO_LIWe recorded neural activity from V1 of freely moving mice before and after administration of the psychedelic DOI. C_LIO_LIDOI had diverse effects on visual response amplitude following a gaze shift, with some neurons increasing while others decreased. C_LIO_LIThe modulation of responses was temporally dynamic, shifting across the response sequence. C_LIO_LILonger latency neurons, which preferentially encode high spatial frequency information, were more consistently suppressed C_LIO_LITogether these effects result in a disruption of population response and coarse-to-fine processing, providing potential mechanisms for altered visual perception C_LI

neuroscience↗

bioRxiv2025

Neural dynamics in superior colliculus of freely moving mice

Vision is an active process that depends on head and eye movements to explore the visual environment. Superior colliculus (SC) is known for its role in generating these movements, as well as processing visual information, but has not been studied extensively during free movement in complex visual environments. To determine the impact of active vision, we recorded neural activity across the depth of SC during free movement while simultaneously recording eye and head position. We find that superficial SC (sSC) neurons respond to visual input following gaze-shifting saccadic movements, whereas deep SC (dSC) neurons respond to the movements themselves, as demonstrated by their sustained response in darkness. Additionally, we find motor responses in dSC are more correlated to head movements rather than eye movements. Furthermore, we compared sSC gaze shift responses to known gaze shift responses in primary visual cortex (V1), finding similarities in key response types, although the temporal sequences following gaze shifts differ between the regions. Our results demonstrate distinct visual processing differences between SC and V1 as well as highlighting the various roles SC plays during active vision. HighlightsO_LIWe recorded neural activity across the depths of superior colliculus (SC) in freely moving mice while measuring head and eye movements. C_LIO_LINeurons in mouse SC respond strongly to gaze shifts, and these responses differ between superficial (sSC) and deep (dSC) layers. C_LIO_LIsSC neurons respond primarily to the visual input during a saccadic movement. C_LIO_LIdSC neurons generally represent the head movement more than the eye movement, independent of visual input. C_LIO_LIWhile sSC gaze shift responses share similarities with V1 there are unique response profiles in SC that suggest differences in the role of visual processing between SC and V1 during free movement. C_LI

neuroscience↗

bioRxiv2023

Multimodal Deep Learning Model Unveils Behavioral Dynamics of V1 Activity in Freely Moving Mice

Despite their immense success as a model of macaque visual cortex, deep convolutional neural networks (CNNs) have struggled to predict activity in visual cortex of the mouse, which is thought to be strongly dependent on the animals behavioral state. Furthermore, most computational models focus on predicting neural responses to static images presented under head fixation, which are dramatically different from the dynamic, continuous visual stimuli that arise during movement in the real world. Consequently, it is still unknown how natural visual input and different behavioral variables may integrate over time to generate responses in primary visual cortex (V1). To address this, we introduce a multimodal recurrent neural network that integrates gaze-contingent visual input with behavioral and temporal dynamics to explain V1 activity in freely moving mice. We show that the model achieves state-of-the-art predictions of V1 activity during free exploration and demonstrate the importance of each component in an extensive ablation study. Analyzing our model using maximally activating stimuli and saliency maps, we reveal new insights into cortical function, including the prevalence of mixed selectivity for behavioral variables in mouse V1. In summary, our model offers a comprehensive deep-learning framework for exploring the computational principles underlying V1 neurons in freely-moving animals engaged in natural behavior.

neuroscience↗

bioRxiv2023

Functional organization of visual responses in the octopus optic lobe

Cephalopods are highly visual animals with camera-type eyes, large brains, and a rich repertoire of visually guided behaviors. However, the cephalopod brain evolved independently from that of other highly visual species, such as vertebrates, and therefore the neural circuits that process sensory information are profoundly different. It is largely unknown how their powerful but unique visual system functions, since there have been no direct neural measurements of visual responses in the cephalopod brain. In this study, we used two-photon calcium imaging to record visually evoked responses in the primary visual processing center of the octopus central brain, the optic lobe, to determine how basic features of the visual scene are represented and organized. We found spatially localized receptive fields for light (ON) and dark (OFF) stimuli, which were retinotopically organized across the optic lobe, demonstrating a hallmark of visual system organization shared across many species. Examination of these responses revealed transformations of the visual representation across the layers of the optic lobe, including the emergence of the OFF pathway and increased size selectivity. We also identified asymmetries in the spatial processing of ON and OFF stimuli, which suggest unique circuit mechanisms for form processing that may have evolved to suit the specific demands of processing an underwater visual scene. This study provides insight into the neural processing and functional organization of the octopus visual system, highlighting both shared and unique aspects, and lays a foundation for future studies of the neural circuits that mediate visual processing and behavior in cephalopods. HighlightsO_LIThe functional organization and visual response properties of the cephalopod visual system are largely unknown C_LIO_LIUsing calcium imaging, we performed mapping of visual responses in the octopus optic lobe C_LIO_LIVisual responses demonstrate localized ON and OFF receptive fields with retinotopic organization C_LIO_LION/OFF pathways and size selectivity emerge across layers of the optic lobe and have distinct properties relative to other species C_LI

neuroscience↗

bioRxiv2022

A dynamic sequence of visual processing initiated by gaze shifts

Animals move their head and eyes as they explore and sample the visual scene. Previous studies have demonstrated neural correlates of head and eye movements in rodent primary visual cortex (V1), but the sources and computational roles of these signals are unclear. We addressed this by combining measurement of head and eye movements with high density neural recordings in freely moving mice. V1 neurons responded primarily to gaze shifts, where head movements are accompanied by saccadic eye movements, but not to head movements where compensatory eye movements stabilize gaze. A variety of activity patterns immediately followed gaze shifts, including units with positive, biphasic, or negative responses, and together these responses formed a temporal sequence following the gaze shift. These responses were greatly diminished in the dark for the vast majority of units, replaced by a uniform suppression of activity, and were similar to those evoked by sequentially flashed stimuli in head-fixed conditions, suggesting that gaze shift transients represent the temporal response to the rapid onset of new visual input. Notably, neurons responded in a sequence that matches their spatial frequency preference, from low to high spatial frequency tuning, consistent with coarse-to-fine processing of the visual scene following each gaze shift. Recordings in foveal V1 of freely gazing head-fixed marmosets revealed a similar sequence of temporal response following a saccade, as well as the progression of spatial frequency tuning. Together, our results demonstrate that active vision in both mice and marmosets consists of a dynamic temporal sequence of neural activity associated with visual sampling. HighlightsO_LIDuring free movement, neurons in mouse V1 respond to head movements that are accompanied by a gaze-shifting saccadic eye movement, but not a compensatory eye movement. C_LIO_LINeurons respond to gaze shifts with diverse temporal dynamics that form a sequence across the population, from early positive responses to biphasic and negative responses. C_LIO_LIIn darkness, most neurons show a uniform suppression following a gaze shift. C_LIO_LITemporal dynamics of responses correspond to a neurons temporal and spatial frequency preferences, consistent with a coarse-to-fine processing sequence. C_LIO_LIA similar temporal sequence following saccades is observed in foveal V1 of freely gazing head-fixed marmosets, demonstrating shared aspects of active visual processing across species. C_LI

neuroscience↗

bioRxiv2022

Cell types and molecular architecture of the octopus visual system

Cephalopods have a remarkable visual system, with a camera-type eye, high acuity vision, and a wide range of sophisticated visual behaviors. However, the cephalopod brain is organized dramatically differently from that of vertebrates, as well as other invertebrates, and little is known regarding the cell types and molecular determinants of their visual system organization beyond neuroanatomical descriptions. Here we present a comprehensive single-cell molecular atlas of the octopus optic lobe, which is the primary visual processing structure in the cephalopod brain. We combined single-cell RNA sequencing with RNA fluorescence in situ hybridization to both identify putative molecular cell types and determine their anatomical and spatial organization within the optic lobe. Our results reveal six major neuronal cell classes identified by neurotransmitter/neuropeptide usage, in addition to non-neuronal and immature neuronal populations. Moreover, we find that additional markers divide these neuronal classes into subtypes with distinct anatomical localizations, revealing cell type diversity and a detailed laminar organization within the optic lobe. We also delineate the immature neurons within this continuously growing tissue into subtypes defined by evolutionarily conserved fate specification genes as well as novel cephalopod- and octopus-specific genes. Together, these findings outline the organizational logic of the octopus visual system, based on functional determinants, laminar identity, and developmental markers/pathways. The resulting atlas presented here delineates the "parts list" of the neural circuits used for vision in octopus, providing a platform for investigations into the development and function of the octopus visual system as well as the evolution of visual processing. HighlightsO_LISingle-cell RNA sequencing coupled with RNA fluorescence in situ hybridization produces a molecular taxonomy of cell types in the octopus visual system. C_LIO_LISix major neuronal cell classes are delineated based on neurotransmitters/neuropeptides, and are further subdivided based on laminar organization and additional marker genes. C_LIO_LIImmature neurons are divided into multiple transcriptional subgroups that correspond to mature cell types, delineated by expression of genes known for their developmental roles in other organisms as well as apparent novel genes. C_LIO_LIThis atlas provides the foundation for future studies of the function, development, and comparative evolution of visual processing in cephalopods. C_LI

neuroscience↗

bioRxiv2022

Joint coding of visual input and eye/head position in V1 of freely moving mice

SUMMARYVisual input to the brain during natural behavior is highly dependent on movements of the eyes, head, and body. Neurons in mouse primary visual cortex (V1) respond to eye and head movements, but how information about eye and head position is integrated with visual processing during free movement is unknown, since visual physiology is generally performed under head-fixation. To address this, we performed single-unit electrophysiology in V1 of freely moving mice while simultaneously measuring the mouses eye position, head orientation, and the visual scene from the mouses perspective. Based on these measures we were able to map spatiotemporal receptive fields during free movement, using a generalized linear model (GLM) that predicted the activity of V1 neurons based on gaze-corrected visual input. Furthermore, we found that a significant fraction of visually-responsive neurons showed tuning for eye position and head orientation. Incorporating these variables into the GLM revealed that visual and positional signals are integrated through a multiplicative mechanism in the majority of modulated neurons, consistent with computation via gain fields and nonlinear mixed selectivity. These results provide new insight into coding in mouse V1, and more generally provide a paradigm for performing visual physiology under natural conditions, including active sensing and ethological behavior. HIGHLIGHTSO_LINeurons in mouse V1 respond to both vision and self-motion, but it is unclear how these are combined. C_LIO_LIWe record neural activity in V1 concurrent with measurement of the visual input from the mouses perspective during free movement. C_LIO_LIThese data provide the first measurement of visual receptive fields in freely moving animals. C_LIO_LIWe show that many V1 neurons are tuned to eye position and head orientation, and these contribute a multiplicative gain on visual responses in the majority of modulated neurons. C_LI

neuroscience↗

bioRxiv2021

Distance estimation from monocular cues in an ethological visuomotor task

In natural contexts, sensory processing and motor output are closely coupled, which is reflected in the fact that many brain areas contain both sensory and movement signals. However, standard reductionist paradigms decouple sensory decisions from their natural motor consequences, and head-fixation prevents the natural sensory consequences of self-motion. In particular, movement through the environment provides a number of depth cues beyond stereo vision that are poorly understood. To study the integration of visual processing and motor output in a naturalistic task, we investigated distance estimation in freely moving mice. We found that mice use vision to accurately jump across a variable gap, thus directly coupling a visual computation to its corresponding ethological motor output. Monocular eyelid suture did not affect gap jumping success, thus mice can use cues that do not depend on binocular disparity and stereo vision. Under monocular conditions, mice altered their head positioning and performed more vertical head movements, consistent with a shift from using stereopsis to other monocular cues, such as motion or position parallax. Finally, optogenetic suppression of primary visual cortex impaired task performance under both binocular and monocular conditions when optical fiber placement was localized to binocular or monocular zone V1, respectively. Together, these results show that mice can use monocular cues, relying on visual cortex, to accurately judge distance. Furthermore, this behavioral paradigm provides a foundation for studying how neural circuits convert sensory information into ethological motor output.

neuroscience↗

bioRxiv2020

Dynamics of gaze control during prey capture in freely moving mice

Many studies of visual processing are conducted in unnatural conditions, such as head- and gaze-fixation. As this radically limits natural exploration of the visual environment, there is much less known about how animals actively use their sensory systems to acquire visual information in natural, goal-directed contexts. Recently, prey capture has emerged as an ethologically relevant behavior that mice perform without training, and that engages vision for accurate orienting and pursuit. However, it is unclear how mice target their gaze during such natural behaviors, particularly since, in contrast to many predatory species, mice have a narrow binocular field and lack foveate vision that would entail fixing their gaze on a specific point in the visual field. Here we measured head and bilateral eye movements in freely moving mice performing prey capture. We find that the majority of eye movements are compensatory for head movements, thereby acting to stabilize the visual scene. During head turns, however, these periods of stabilization are interspersed with non-compensatory saccades that abruptly shift gaze position. Analysis of eye movements relative to the cricket position shows that the saccades do not preferentially select a specific point in the visual scene. Rather, orienting movements are driven by the head, with the eyes following in coordination to sequentially stabilize and recenter the gaze. These findings help relate eye movements in the mouse to other species, and provide a foundation for studying active vision during ethological behaviors in the mouse.

neuroscience↗

bioRxiv2019

Effects of nectin-3 misexpression on dendritic spine density during the postnatal development of layer 2/3 cortical neurons

BackgroundDeveloping cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, Nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown. MethodsHere we block Nectin-3 expression (via shRNA) or overexpress Nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35). ResultsKnockdown of Nectin-3 beginning at E15.5 or [~]P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length Nectin-3 at E15.5 led to decreased dendritic spine densities when all ages were considered together. Interestingly, an even greater decrease in dendritic spine densities, particularly at P21, was observed when we overexpressed Nectin-3 lacking its Afadin binding domain, indicating Afadin may facilitate spine morphogenesis after eye opening. ConclusionThese data collectively suggest that the proper levels of Nectin-3, as well as the interaction of Nectin-3 with Afadin, facilitate normal synapse formation after eye opening in layer 2/3 visual cortical neurons.

neuroscience↗

bioRxiv2019

Defined cell types in superior colliculus make distinct contributions to prey capture behavior in the mouse

The superior colliculus (SC) mediates rapid orienting to visual stimuli across species. To determine the specific circuits within the SC that drive orienting and approach behavior toward appetitive stimuli, we explored the role of three genetically defined cell types in mediating prey capture in mice. Chemogenetic inactivation of two classically defined cell types, the wide-field (WF) and narrow-field (NF) vertical neurons, revealed that they are involved in distinct aspects of prey capture. WF neurons were required for rapid prey detection and distant approach initiation, whereas NF neurons were required for continuous and accurate orienting during pursuit. In contrast, prey capture did not require parvalbumin-expressing (PV) neurons that have previously been implicated in fear responses. The visual coding of WF and NF cells in the awake mouse and their projection targets were consistent with their roles in prey detection versus pursuit. Thus, our studies link specific neural circuit connectivity and function with stimulus detection and orienting behavior, providing insight into visuomotor and attentional mechanisms mediated by superior colliculus.\n\nHighlightsO_LIThis study provides the first demonstration of the role of specific cell populations in the superior colliculus in orienting and approach behavior.\nC_LIO_LIA genetically targeted population of wide-field vertical neurons in the superior colliculus is required for rapid prey detection and initiation of long-distance approaches.\nC_LIO_LIA genetically targeted population of narrow-field vertical neurons is required for approach initiation, accurate targeting, and approach continuity.\nC_LIO_LIVisual response properties and projection targets of these cells are consistent with their role in prey capture, linking neural circuit connectivity and function with behavior.\nC_LI

neuroscience↗

bioRxiv2019

Distinct functional classes of excitatory neurons in mouse V1 are differentially modulated by learning and task engagement

Learning can cause significant changes in neural responses to relevant stimuli, in addition to modulation due to task engagement. However, it is not known how different functional types of excitatory neurons contribute to these changes. To address this gap, we performed two-photon calcium imaging of excitatory neurons in layer 2/3 of mouse primary visual cortex before and after learning of a visual discrimination. We found that excitatory neurons show striking diversity in the temporal dynamics of their response to visual stimuli during the behavior, and based on this we classified them into transient, sustained, and suppressed groups. Notably, these functionally defined cell classes exhibit different visual stimulus selectivity and modulation by locomotion, and were differentially affected by training condition. In particular, we observed a decrease in the number of transient neurons responsive during behavior after learning, while both transient and sustained cells showed an increase in modulation due to task engagement after learning. The identification of functional diversity within the excitatory population, with distinct changes during learning and task engagement, provides insight into the cortical pathways that allow context-dependent neural representations.

neuroscience↗