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Saleem, A. B.

Publications and source records attributed to Saleem, A. B..

14 recordsLinked to original sources

Gait kinematics dynamically tune optic flow motion-in-depth perception during human locomotion

Behavior generates continuous sensorimotor contingencies that the brain must process. In particular, locomotion produces optic flow, which is frequently noisy and ambiguous during navigation. Integrating non-visual self-motion signals can therefore provide a computational advantage to resolve this sensory uncertainty. To investigate this we developed a novel head-mounted 3D motion coherence paradigm. We found that walking dissociably alters perceptual sensitivity and bias for optic flow, dependent on stimulus speed. Rather than acting as a binary state change, these modulations scale dynamically with step frequency. While slow stepping impairs sensitivity to optic flow, fast stepping rescues this deficit. Simultaneously, higher step frequencies drive a progressive shift in perceptual bias, consistent with canceling expected self-generated flow. Our results indicate that optic flow perception during locomotion is modulated by active processes, encompassing both discrete behavioral state changes and continuous, dynamic sensorimotor integration. Broadly, these findings demonstrate that the brain leverages natural contingencies between behavior and expected sensory feedback to actively modulate perception.

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Interplay of sleep neural oscillations enhances coordinated memory reactivation between cortex and hippocampus

Memory consolidation during sleep requires coordinated reactivation of specific experiences across hippocampus and cortex. This process occurs with synchronized neural oscillations including cortical slow waves, thalamocortical spindles, and hippocampal sharp-wave ripples. While temporal coupling of these rhythms is implicated in consolidation, a fundamental question remains: do oscillations reflect a general increase in communication, or do they selectively coordinate which memories are reactivated together across regions? Here we segregated competing memory representations in primary visual cortex by training mice on two visually distinct virtual reality tracks, each restricted to one visual hemifield, rendering their representations lateralized in cortex. Using large-scale electrophysiology, we demonstrate that hippocampus and cortex coherently reactivate the same memories. Temporally, the cortical memory trace active before and after a ripple is coherent with the memory hippocampus reactivates. Crucially, this reactivation coherence is maximally enhanced by high hippocampal ripple power in concert with high cortical spindle-band power and slow oscillation trough phase localized to the dominant memory trace reactivating. Our findings establish that sleep oscillations coordinate content-specific cortico-hippocampal reactivation necessary for consolidation.

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Locomotion selectively enhances visual speed encoding in mouse medial higher visual areas

Mammalian visual systems are comprised of multiple brain areas with distinct functional roles. Whilst functional specialisations have been proposed in the mouse based on visual feature encoding, the extent to which these specialisations are contingent on ongoing behaviour is unknown. To address this we analysed neural encoding of visual motion stimuli by thousands of neurons recorded across six cortical and two thalamic mouse visual areas while mice were stationary or locomoting. We found locomotion selectively enhanced visual speed encoding in medial higher visual cortical areas, indicating that these areas may be specialised for the processing visual motion during locomotion. By contrast, encoding of drifting gratings direction was enhanced non-selectively across the mouse visual cortex during locomotion. Our results therefore reveal how a complex interplay of sensory input and ongoing behaviour differentially shapes the efficacy of sensory processing in mouse higher visual areas.

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Loom response in mouse superior colliculus depends on sensorimotor context

Visual motion is produced both by an organisms movement through the world, and by objects moving in the world such as potential predators. Choosing appropriate behaviour therefore requires organisms to distinguish these sources of visual motion. Here we asked how mice integrate self-movement with looming visual motion by combining virtual reality and neural recordings from superior colliculus (SC), a brain area important in visually-guided approach and avoidance behaviours. We first measured locomotion behaviour and neural activity while animals approached an object in virtual reality, and while the same object loomed at them. In both cases, vision dominated activity in superficial layers (SCs), while locomotion had more influence on activity in intermediate layers (SCim). In addition, animals instinctively slowed their locomotion when nearing the object, or when the object neared them. To directly test animals ability to distinguish self-from object motion we replayed the visual images generated during object approach. Locomotion behaviour often changed during replay, showing animals are able to establish if visual motion is matched to their self-movement. Further, decoders trained on locomotion behaviour, or on population activity in SC, particularly in SCim, were able to reliably discriminate epochs of replay and object approach. We conclude that both mouse behaviour and SC activity encode whether looming visual motion arises from self-or object movement, with implications for understanding sensorimotor coordination in dynamic environments. HighlightsO_LIWe recorded from superficial (SCs) and intermediate (SCim) superior colliculus in VR C_LIO_LIVision dominated SCs, while SCim was modulated by both vision and locomotion C_LIO_LIMice altered behaviour when visual experience did not match that expected from their locomotion C_LIO_LIPopulation activity differed between matched and unmatched visual experiences, particularly in SCim C_LI

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Altered low frequency brain rhythms precede changes in gamma power during tauopathy

Alzheimers disease and other dementias are associated with disruptions of electrophysiological brain activity, including low frequency and gamma rhythms. Many of these dementias are also associated with the malfunction of the membrane associated protein tau. Tauopathy disrupts neuronal function and the stability of synapses and is a key driver of neurodegeneration. Here we ask how brain rhythms are affected by tauopathy, at different stages of its progression. We performed local field potential recordings from visual cortex of rTg4510 and control animals at early stages of neurodegeneration (5 months) and at a more advanced stage where pathology is evident (8 months). We measured brain activity in the presence or absence of external visual stimulation, and while monitoring pupil diameter and locomotion to establish animal behavioural states. At 5 months, before substantial pathology, we found an increase in low frequency rhythms during resting state in tauopathic animals. This was because tauopathic animals entered intermittent periods of increased neural synchronisation, where activity across a wide band of low frequencies was strongly correlated. At 8 months, when the degeneration was more advanced, the increased synchronisation and low frequency power was accompanied by a reduction in power in the gamma range, with diverse effects across different components of the gamma rhythm. Our results indicate that slower rhythms are impaired earlier than gamma rhythms in tauopathy, suggesting that electrophysiological measurements can indicate both the presence and progression of tauopathic degeneration.

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Distinct neural dynamics underlie the encoding of visual speed in stationary and running mice

Sensory experiences are often driven by an animals self-motion and locomotion is known to modulate neural responses in the mouse visual system. This modulation is hypothesised to improve the processing of behaviourally relevant visual inputs, which may change rapidly during locomotion. However, little is known about how locomotion modulates the temporal dynamics (time courses) of visually-evoked neural responses. Here, we analysed the temporal dynamics of single neuron and population responses to dot field stimuli moving at a range of visual speeds using the Visual Coding dataset from the Allen Institute for Brain Science1. Single neuron responses had diverse temporal dynamics that varied between stationary and running sessions. Increased dynamic range and more reliable responses in running sessions enabled faster, stronger and more persistent encoding of visual speed. Population activity reflected the temporal dynamics of single neuron responses, including their modulation by locomotor state - neural trajectories of population activity made more direct transitions between baseline and stimulus steady states in running sessions. The structure of population coding also changed with locomotor state - population activity prioritised the encoding of visual speed in running, but not stationary sessions. Our results reveal a profound influence of locomotion on the temporal dynamics of neural responses. We demonstrate that during locomotion, mouse visual areas prioritise the encoding of potentially fast-changing, behaviourally relevant visual features.

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Feature selectivity explains mismatch signals in mouse visual cortex

Sensory experience is often dependent on ones own actions, including self-motion. Theories of predictive coding postulate that actions are regulated by calculating prediction error, which is the difference between sensory experience and expectation based on self-generated actions. Signals consistent with prediction error have been reported in mouse visual cortex (V1) when visual flow coupled to running is unexpectedly perturbed. Here, we show that such signals can be elicited by visual stimuli uncoupled with the animals running. We recorded the activity of mouse V1 neurons while presenting drifting gratings that unexpectedly stopped. We found strong responses to visual perturbations, which were enhanced during running. If these perturbation responses are signals about sensorimotor mismatch, they should be largest for front-to-back visual flow expected from the animals running. Responses, however, did not show a bias for front-to-back visual flow. Instead, perturbation responses were strongest in the preferred orientation of individual neurons and perturbation responsive neurons were more likely to prefer slow visual speeds. Our results therefore indicate that prediction error signals can be explained by the convergence of known motor and sensory signals in visual cortex, providing a purely sensory and motor explanation for purported mismatch signals.

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Midbrain dopamine neurons provide teaching signals for goal-directed navigation

In naturalistic environments, animals navigate in order to harvest rewards. Successful goal-directed navigation requires learning to accurately estimate location and select optimal state-dependent actions. Midbrain dopamine neurons are known to be involved in reward value learning1-13. They have also been linked to reward location learning, as they play causal roles in place preference14,15 and enhance spatial memory16-21. Dopamine neurons are therefore ideally placed to provide teaching signals for goal-directed navigation. To test this, we imaged dopamine neural activity as mice learned to navigate in a closed-loop virtual reality corridor and lick to report the reward location. Across learning, phasic dopamine responses developed to visual cues and trial outcome that resembled reward prediction errors and indicated the animals estimate of the reward location. We also observed the development of pre-reward ramping activity, the slope of which was modulated by both learning stage and task engagement. The slope of the dopamine ramp was correlated with the accuracy of licks in the next trial, suggesting that the ramp sculpted accurate location-specific action during navigation. Our results indicate that midbrain dopamine neurons, through both their phasic and ramping activity, provide teaching signals for improving goal-directed navigation. HighlightsO_LIWe investigated midbrain dopamine activity in mice learning a goal-directed navigation task in virtual reality C_LIO_LIPhasic dopamine signals reflected prediction errors with respect to subjective estimate of reward location C_LIO_LIA slow ramp in dopamine activity leading up to reward location developed over learning and was enhanced with task engagement C_LIO_LIPositive ramp slopes were followed by improved performance on subsequent trials, suggesting a teaching role during goal-directed navigation C_LI

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Plasticity in visual cortex is disrupted in a mouse model of tauopathy and neurodegeneration

Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease. HighlightsO_LIVisual plasticity is disrupted at early stages of neurodegeneration in rTg4510 mice C_LIO_LIVisual plasticity is reduced in older animals, particularly during neurodegeneration C_LIO_LIInstinctive visual behaviours are reduced in neurodegeneration C_LIO_LIShort-term visual plasticity is reduced in neurodegeneration C_LI

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Spatial modulation of dark versus bright stimulus responses in mouse visual cortex

A fundamental task of the visual system is to respond to luminance increments and decrements. In primary visual cortex (V1) of cats and primates, luminance decrements elicit stronger, faster, and more salient neural activity (OFF responses) than luminance increments (ON responses). However, studies of V1 in ferrets and mice show that ON responses may be stronger. These discrepancies may arise from differences in species, experimental conditions, or from measuring responses in single neurons versus populations. Here, we examined OFF versus ON responses across different regions of visual space in both single neurons and populations of mouse V1. We used high-density silicon probes and whole-cell patch-clamp recordings to assess OFF versus ON dominance in local field potential (LFP), single neuron, and membrane potential responses. Across these levels, we found that OFF responses clearly dominated in the central visual field, whereas ON responses were more evident in the periphery. These observations were clearest in LFP and subthreshold membrane potential. Our findings consolidate and resolve prior conflicting results and reveal that retinotopy may provide a common organizing principle for spatially biasing OFF versus ON processing in mammalian visual systems.

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BonVision - an open-source software to create and control visual environments

Real-time rendering of closed-loop visual environments is necessary for next-generation understanding of brain function and behaviour, but is prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks and communication with behavioural and physiological measurement and manipulation devices.

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Modulation of visual cortex by hippocampal signals

Neurons in primary visual cortex (V1) are influenced by the animals position in the environment and encode positions that correlate with those encoded by hippocampus (CA1). Might V1s encoding of spatial positions be inherited from hippocampal regions? If so, it should depend on non-visual factors that affect the encoding of position in hippocampus, such as the physical distance traveled and the phase of theta oscillations. We recorded V1 and CA1 neurons while mice ran through a virtual corridor and confirmed these predictions. Spatial representations in V1 and CA1 were correlated even in the absence of visual cues. Moreover, similar to CA1 place cells, the spatial responses of V1 neurons were influenced by the physical distance traveled and the phase of hippocampal theta oscillations. These results reveal a modulation of cortical sensory processing by non-sensory estimates of position that might originate in hippocampal regions.

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Layer-specific integration of locomotion and concurrent wall touching in mouse barrel cortex

During navigation rodents continually sample the environment with their whiskers. How locomotion modulates neuronal activity in somatosensory cortex and how self-motion is integrated with whisker touch remains unclear. Here, we used calcium imaging in mice running in a tactile virtual reality to investigate modulation of neurons in layer 2/3 (L2/3) and L5 of barrel cortex. About a third of neurons in both layers increased activity during running and concomitant whisking, in the absence of touch. Fewer neurons were modulated by whisking alone (<10%). Whereas L5 neurons responded transiently to wall-touching during running, L2/3 neurons showed sustained activity after touch onset. Consistently, neurons encoding running-with-touch were more abundant in L2/3 compared to L5. Few neurons across layers were also sensitive to abrupt perturbations of tactile flow. We propose that L5 neurons mainly report changes in touch conditions whereas L2/3 neurons continually monitor ongoing tactile stimuli during running.

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Coherent representations of subjective spatial position in primary visual cortex and hippocampus

A major role of vision is to guide navigation, and navigation is strongly driven by vision1-4. Indeed, the brains visual and navigational systems are known to interact5, 6, and signals related to position in the environment have been suggested to appear as early as in visual cortex6, 7. To establish the nature of these signals we recorded in primary visual cortex (V1) and in the CA1 region of the hippocampus while mice traversed a corridor in virtual reality. The corridor contained identical visual landmarks in two positions, so that a purely visual neuron would respond similarly in those positions. Most V1 neurons, however, responded solely or more strongly to the landmarks in one position. This modulation of visual responses by spatial location was not explained by factors such as running speed. To assess whether the modulation is related to navigational signals and to the animals subjective estimate of position, we trained the mice to lick for a water reward upon reaching a reward zone in the corridor. Neuronal populations in both CA1 and V1 encoded the animals position along the corridor, and the errors in their representations were correlated. Moreover, both representations reflected the animals subjective estimate of position, inferred from the animals licks, better than its actual position. Indeed, when animals licked in a given location - whether correct or incorrect - neural populations in both V1 and CA1 placed the animal in the reward zone. We conclude that visual responses in V1 are tightly controlled by navigational signals, which are coherent with those encoded in hippocampus, and reflect the animals subjective position in the environment. The presence of such navigational signals as early as in a primary sensory area suggests that these signals permeate sensory processing in the cortex.

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