Synchronizing retinal activity in both eyes disrupts binocular map development in the optic tectum

Spatiotemporal correlations in the pattern of spontaneous and evoked retinal ganglion cell (RGC) activity are believed to influence the topographic organization of connections throughout the developing visual system. We have tested this hypothesis by examining the effects of interfering with these potential activity cues during development on the functional organization of binocular maps in the Xenopus frog optic tectum. Paired recordings combined with cross-correlation analyses demonstrated that exposing normal frogs to a continuous 1 Hz of stroboscopic illumination synchronized the firing of all three classes of RGC projecting to the tectum and induced similar patterns of temporally correlated activity across both lobes of the nucleus. Embryonic and eye-rotated larval animals were reared until early adulthood under equivalent stroboscopic conditions. The maps formed by each RGC class in the contralateral tectum showed normal topography and stratification after strobe rearing, but with consistently enlarged multiunit receptive fields. Maps of the ipsilateral eye, formed by crossed isthmotectal axons, showed significant disorder and misalignment with direct visual input from the retina, and in the eye-rotated animals complete compensatory reorientation of these maps usually induced by this procedure failed to occur. These findings suggest that refinement of retinal arbors in the tectum and the ability of crossed isthmotectal arbors to establish binocular convergence with these retinal afferents are disrupted when they all fire together. Our data thus provide direct experimental evidence that spatiotemporal activity patterns within and between the two eyes regulate the precision of their developing connections

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Binocular interactions underlying the classic optomotor responses of flying flies.

In response to imposed course deviations, the optomotor reactions of animals reduce motion blur and facilitate the maintenance of stable body posture. In flies, many anatomical and electrophysiological studies suggest that disparate motion cues stimulating the left and right eyes are not processed in isolation but rather are integrated in the brain to produce a cohesive panoramic percept. To investigate the strength of such inter-ocular interactions and their role in compensatory sensory-motor transformations, we utilize a virtual reality flight simulator to record wing and head optomotor reactions by tethered flying flies in response to imposed binocular rotation and monocular front-to-back and back-to-front motion. Within a narrow range of stimulus parameters that generates large contrast insensitive optomotor responses to binocular rotation, we find that responses to monocular front-to-back motion are larger than those to panoramic rotation, but are contrast sensitive. Conversely, responses to monocular back-to-front motion are slower than those to rotation and peak at the lowest tested contrast. Together our results suggest that optomotor responses to binocular rotation result from the influence of non-additive contralateral inhibitory as well as excitatory circuit interactions that serve to confer contrast insensitivity to flight behaviors influenced by rotatory optic flow

Temporal and spatial distortions in adult amblyopia

Amblyopia is a developmental disorder of the visual system that leads to reduced vision in one or both eyes. People suffering from amblyopia show different perceptual deficits like reduced contrast sensitivity, reduced or no stereopsis, spatial uncertainty, and spatial and temporal distortions when viewing with the amblyopic eye. In the following thesis, different psychophysical methods are used to investigate anomalous perception of amblyopic participants in detail with the main focus on the perception of temporal instability. In the qualitative experimental paradigms it is shown that temporal instability is mainly perceived by strabismic and strabismic-anisometropic amblyopes. The temporal deficits occur only at spatial frequencies higher than 1.6 c/deg, and are perceived in addition to the spatial distortions. Illusory colours sometimes accompany the temporal distortions. There seems to be a relationship between crossed hand and eye dominance and the perception of temporal instability. In the quantitative experiments it is shown that temporal instability in amblyopic perception has a negative impact on the performance in psychophysical tasks. Amblyopes perceiving temporal instability show enhanced spatial uncertainty and spatial distortions for different types of stimulus presentation (auditive vs. visual) when compared to amblyopes without temporal instability. This might be due to deficits in auditive-visual mapping. These deficits in auditory-to-visual mapping suggest an impairment of the dorsal “where” pathway. Thus, it might be that amblyopes with temporal distortions have deficits in the dorsal pathway that come up in addition to the known deficits of the ventral “what” pathway and are related to the perception of temporal instability. The different results of the experiments found in this thesis seem to confirm this hypothesis. Studies using functional imaging techniques might be appropriate for a further investigation of amblyopic deficits involving the dorsal pathway

Mechanisms of Experience-dependent Prevention of Plasticity in Visual Circuits

Development of brain function is instructed by both genetically-determined processes (nature) and environmental stimuli (nurture). The relative importance of nature and nurture is a major question in developmental neurobiology. In this dissertation, I investigated the role of visual experience in the development and plasticity of the visual pathway. Each neuron that receives visual input responds to a specific area of the visual field- their receptive field (RF). Developmental refinement reduces RF size and underlies visual acuity, which is important for survival. By rearing Syrian hamsters (Mesocricetus auratus) in constant darkness (dark rearing, DR) from birth, I investigated the role of visual experience in RF refinement and plasticity. Previous work in this lab has shown that developmental refinement of RFs occurs in the absence of visual experience in the superior colliculus (SC), but that RFs unrefine and thus enlarge in adulthood during chronic DR. Using an in vivo electrophysiological approach, I show that, contrary to a widely held view, visual experience is not necessary for refinement of RFs in primary visual cortex (V1). In both SC and V1, RFs refine by postnatal day (P) 60, but enlarge by P90 with chronic DR. One week of visual experience was sufficient to prevent RF enlargement in SC and V1. How normal sensory experience prevents plasticity in mature circuits is not well understood. Using an in vitro electrophysiological approach, I demonstrated that GABAergic inhibition is reduced in DR SC, which in turn affects short-term (but not long-term) synaptic plasticity. The level of GABABR-mediated short-term synaptic depression (STD) that occurs during high-frequency afferent stimulation, such as occurs during vision, is reduced by DR. Using a computational model of RF size, I propose that, in addition to the effect of reduced inhibition, reduced STD of excitation could contribute to enlarged RFs. This work provides insight into mechanisms of development and plasticity of the nervous system. How plasticity is restricted in mature circuits is of fundamental importance in neuroscience and could instruct therapies to prevent maladaptive plasticity in disease and to enhance recovery of function in adults

Binocular fusion and invariant category learning due to predictive remapping during scanning of a depthful scene with eye movements

How does the brain maintain stable fusion of 3D scenes when the eyes move? Every eye movement causes each retinal position to process a different set of scenic features, and thus the brain needs to binocularly fuse new combinations of features at each position after an eye movement. Despite these breaks in retinotopic fusion due to each movement, previously fused representations of a scene in depth often appear stable. The 3D ARTSCAN neural model proposes how the brain does this by unifying concepts about how multiple cortical areas in the What and Where cortical streams interact to coordinate processes of 3D boundary and surface perception, spatial attention, invariant object category learning, predictive remapping, eye movement control, and learned coordinate transformations. The model explains data from single neuron and psychophysical studies of covert visual attention shifts prior to eye movements. The model further clarifies how perceptual, attentional, and cognitive interactions among multiple brain regions (LGN, V1, V2, V3A, V4, MT, MST, PPC, LIP, ITp, ITa, SC) may accomplish predictive remapping as part of the process whereby view-invariant object categories are learned. These results build upon earlier neural models of 3D vision and figure-ground separation and the learning of invariant object categories as the eyes freely scan a scene. A key process concerns how an object's surface representation generates a form-fitting distribution of spatial attention, or attentional shroud, in parietal cortex that helps maintain the stability of multiple perceptual and cognitive processes. Predictive eye movement signals maintain the stability of the shroud, as well as of binocularly fused perceptual boundaries and surface representations.Published versio

A comparative study of cortical computations in the mammalian visual cortex

textA common feature of all mammals is the cerebral cortex, which is essential for higher-order functions and processing information to generate motor actions. While cortical circuits exhibit a striking uniformity in anatomical organization, it is unknown whether these circuits preform similar computations across mammalian species. In this dissertation I compare the emergence of two computations in the primary visual cortex (V1) of carnivores and rodents. A cortical computation is a transformation in neural representation, such that the spiking output of a cortical neuron exhibits a selectivity not present in the inputs from upstream neurons. Here I explore two computations: orientation selectivity, the preference of neurons for oriented edges in the visual world, and binocularity, the integration of signals from the two eyes. In the first section, I compare the emergence of orientation selectivity in the early visual pathway of mouse and cat. Recordings from thalamic relay cells and V1 neurons in both species reveal orientation selectivity in mouse V1 is not emergent, and could be inherited subcortically. In a second set of experiments, I measure orientation selectivity and the organization of V1 orientation preference in a grasshopper mouse with predatory behavior, compared to the scavenger lab mouse. Here I find the same functional properties. In the second section, I focus on the integration of ocular inputs in V1 of mouse and cat. I first compare disparity selectivity in cats, where convergence of ocular inputs has long been established, with mice, where ocular integration had not previously been investigated. Similar to cats, mouse V1 neurons were sensitive to binocular disparity, albeit to a lesser degree, and could be described by a linear feed-forward model. I next explore the disruption of binocular disparity tuning in both animals. In cats, strabismus induced during development causes increased monocularity in V1 and a loss of disparity selectivity. In mice, monocular deprivation causes increased ocular input, which also manifests as decreased disparity selectivity. Finally, I explore how excitatory and inhibitory neurons in mouse V1 integrate binocular signals. Paravalbumin-expressing inhibitory interneurons are more binocular but less disparity tuned than surrounding cortical neurons, providing a canonical mechanism explaining loss of disparity selectivity in both carnivores and rodents.Neuroscienc

Computations in the early visual system in the mouse

In this dissertation, I have explored the mechanisms underlying the selectivity of different visual features in the mouse. I have compared these mechanisms to the canonical mechanisms for extracting these features. In chapter 2, I have demonstrated existence of nonclassical receptive fields in which the orientation preference can depend on the spatial frequency, in the mouse visual cortex. I have compared the experimental data with a model based on random connectivity between cells which predicts existence of such receptive fields. In chapter 3, I have studied the input differences between V1 neurons with varying degrees of linearity in spatial summation. I have demonstrated evidence of connectivity which deviates from the standard hierarchical connectivity model. I show that nonlinear cells in the mouse V1 can receive thalamic input which can itself be nonlinear and also orientation selective. In chapter 4, I have studied the development of binocular disparity tuning and using monocular deprivation. I show that disparity selectivity in the mouse is reduced following contralateral eye deprivation during critical period. This effect is due to a disruption of existing disparity selectivity in the circuit following deprivation, as we observe no difference in degree of selectivity between adult animals and young mice before critical period. This disruption may be due to formation of new inputs which disrupt the matching between left and right eye existing inputs. We provide evidence for this by demonstrating a reduction in spatial acuity for the open eye inputs following deprivation. Across all of these studies, I demonstrate multiple instances in which the mouse pathways differ from the classical early visual pathways. But I also find evidence for a distinctive connectivity, similar to the classical models. My thesis highlights the diversity in circuit computations which leads to the processing outcomes that are shared across the mammalian speciesNeuroscienc

Mechanisms Underlying Maintenance of Adult Visual Receptive Fields

The establishment of neuronal connections requires a sequence of orchestrated events including neuronal migration, axon guidance, synapse formation and elimination, and circuit fine-tuning. Understanding the molecular signaling pathways that underlie these processes is fundamental to understanding how the nervous system is assembled and how it functions. In this dissertation, I investigated the molecular mechanisms mediating the effects of visual experience in the development and plasticity of the visual pathway. Each neuron receiving visual input responds to a specific area of the visual field- their receptive field (RF). During early development RFs refine in size, an important property of visual acuity. Utilizing the sensory deprivation model of dark rearing (DR) in Syrian hamsters (Mesocricerus auratus), I investigated the signaling mechanisms underlying RF refinement and plasticity. Our lab has previously reported that the developmental refinement of RFs happens independently of visual experience in both superior colliculus (SC) and visual cortex (V1), but fails to be maintained without sufficient visual experience during an early critical period (CP). Using a pharmacological approach, I show that BDNF/TrkB signaling is crucial for the maintenance of RF refinement in SC. DR hamsters treated with a TrkB agonist during the CP for RF refinement maintenance (P33-P40) have mature RFs in adulthood. Hamsters given visual experience, but treated with a TrkB antagonist during the CP have enlarged (unrefined) RFs in adulthood. I also show that refined RFs are essential for enhancing both looming escape behaviors, and spatial discrimination of sinusoidal gratings. How early visual experience prevents plasticity in adulthood (resulting in a loss of RF maintenance) is poorly understood, but reduced GABAergic inhibition is involved. Using a molecular approach I identified several possible mechanisms mediating a loss of inhibition in SC of DR adults. Ultimately it appears that reduced expression of the GABA neurotransmitter is primarily responsible for loss of RF maintenance, rather than any post synaptic modifications. This work provides insight into the mechanisms of development and plasticity in the nervous system and could instruct therapies to prevent maladaptive plasticity in disease and to enhance recovery of function in adults

Representations of Active Vision

This dissertation focuses on the interplay between visual processing and motor action during natural behaviors, which has previously been limited due to technological constraints in experimental paradigms. However, recent technological innovations have improved the data collection process, enabling a better understanding of visual processing under naturalistic conditions. This dissertation lays out the foundational experimental methods, data analysis, and theoretical modeling to study visual processing during natural behaviors. Chapter II of the dissertation establishes and characterizes how mice change their gaze during prey capture behavior using a miniaturized camera system to simultaneously record the eyes and head as the mice captured crickets. The study finds that there are two types of eye movements during prey capture. The majority of eye movements are compencatory, however there is a subset that shift the gaze of the mouse and are initiated due to head movements in a 'saccade and fixate' strategy. Chapter III, expands upon the previous methods and records neural activity, eye position, head orientation, and visual scene simultaneously while mice freely explore an arena. The data is used to create a model to correct the visual scene for gaze position, enabling the mapping of the first visual receptive fields in a free-moving animal. The study discovers neurons in the primary visual cortex that are tuned to eye position and head orientation, with most cells integrating positional and visual information through a multiplicative gain modulation mechanism. Chapter IV explores mechanisms for computing higher-order visual representations, like distance estimation, from predictions. The study creates a simulated environment where an agent records visual scene, depth maps, and positional information while navigating an arena. A deep convolutional recurrent neural network is trained on the visual scene and tasked with predicting future visual input. Post-training, the study is able to linearly decode the pixel-wise distance of the visual scene without explicit distance information. This work establishes that predictive processing is a viable mechanism for the visual system to learn to create higher-order visual representations without explicit training. This dissertation consists of previously published co-authored material