Seminars

Despite her still poor visual acuity and minimal visual experience, a 2-3 month old baby will reliably respond to facial expressions, smiling back at her caretaker or older sibling. But what if that same baby had been deprived of her early visual experience? Will she be able to appropriately respond to seemingly mundane interactions, such as a peer’s facial expression, if she begins seeing at the age of 10? My work is part of Project Prakash, a dual humanitarian/scientific mission to identify and treat curably blind children in India and then study how their brain learns to make sense of the visual world when their visual journey begins late in life. In my talk, I will give a brief overview of Project Prakash, and present findings from one of my primary lines of research: plasticity of face perception with late sight onset. Specifically, I will discuss a mixed methods effort to probe and explain the differential windows of plasticity that we find across different aspects of distributed face recognition, from distinguishing a face from a nonface early in the developmental trajectory, to recognizing facial expressions, identifying individuals, and even identifying one’s own caretaker. I will draw connections between our empirical findings and our recent theoretical work hypothesizing that children with late sight onset may suffer persistent face identification difficulties because of the unusual acuity progression they experience relative to typically developing infants. Finally, time permitting, I will point to potential implications of our findings in supporting newly-sighted children as they transition back into society and school, given that their needs and possibilities significantly change upon the introduction of vision into their lives.

In most animal species including humans, commissural axons connect neurons on the left and right side of the nervous system. In humans, abnormal axon midline crossing during development causes a whole range of neurological disorders ranging from congenital mirror movements, horizontal gaze palsy, scoliosis or binocular vision deficits. The mechanisms which guide axons across the CNS midline were thought to be evolutionary conserved but our recent results suggesting that they differ across vertebrates. I will discuss the evolution of visual projection laterality during vertebrate evolution. In most vertebrates, camera-style eyes contain retinal ganglion cell (RGC) neurons projecting to visual centers on both sides of the brain. However, in fish, RGCs are thought to only innervate the contralateral side. Using 3D imaging and tissue clearing we found that bilateral visual projections exist in non-teleost fishes. We also found that the developmental program specifying visual system laterality differs between fishes and mammals. We are currently using various strategies to discover genes controlling the development of visual projections. I will also present ongoing work using 3D imaging techniques to study the development of the visual system in human embryo.

I will begin by describing recent research taking a new, model-based approach to perceptual development. This approach uncovers fundamental changes in information processing underlying the protracted development of perception, action, and decision-making in childhood. For example, integration of multiple sensory estimates via reliability-weighted averaging – widely used by adults to improve perception – is often not seen until surprisingly late into childhood, as assessed by both behaviour and neural representations. This approach forms the basis for a newer question: the scope for the nervous system to deploy useful computations (e.g. reliability-weighted averaging) to optimise perception and action using newly-learned sensory signals provided by technology. Our initial model system is augmenting visual depth perception with devices translating distance into auditory or vibro-tactile signals. This problem has immediate applications to people with partial vision loss, but the broader question concerns our scope to use technology to tune in to any signal not available to our native biological receptors. I will describe initial progress on this problem, and our approach to operationalising what it might mean to adopt a new signal comparably to a native sense. This will include testing for its integration (weighted averaging) alongside the native senses, assessing the level at which this integration happens in the brain, and measuring the degree of ‘automaticity’ with which new signals are used, compared with native perception.

Using a combination of in vivo imaging of neuronal circuit functional and structural dynamics, we have investigated the mechanisms by which patterned neural activity and sensory experience alter connectivity in the developing brain. We have identified, in addition to the long-hypothesized Hebbian structural plasticity mechanisms, a kind of plasticity induced by the absence of correlated firing that we dubbed “Stentian plasticity”. In the talk I will discuss the phenomenology and some mechanistic insights regarding Stentian mechanisms in brain development. Further, I will show how glia may have a key role in circuit remodeling during development. These studies have led us to an appreciation of the importance of neuron-glia interactions in early development and the ability of patterned activity to guide circuit wiring.

Claude Desplan is a Silver Professor of Biology and Neuroscience at NYU. He was born in Algeria and was trained at Ecole Normale Supérieure St. Cloud, France. He received his DSc at INSERM in Paris in 1983 and joined Pat O’Farrell at UCSF as a postdoc. There he demonstrated that the homeodomain, a conserved signature of many developmental genes, is a DNA binding motif. Currently, Dr. Desplan works at NYU where he investigates the generation of neural diversity using the Drosophila visual system.

The human visual system enables us to recognize objects (e.g., this is a cup) and act upon them (e.g., grasp the cup) with astonishing ease and accuracy. For decades, it was widely accepted that these different functions rely on two separated cortical pathways. The ventral occipitotemporal pathway subserves object recognition, while the dorsal occipitoparietal pathway promotes visually guided actions. In my talk, I will discuss recent evidence from a series of neuropsychological, developmental and neuroimaging studies that were aimed to explore the nature of object representations in the dorsal pathway. The results from these studies highlight the plausible role of the dorsal pathway in object perception and reveal an interplay between shape representations derived by the two pathways. Together, these findings challenge the binary distinction between the two pathways and are consistent with the view that object recognition is not the sole product of ventral pathway computations, but instead relies on a distributed network of regions.

The long-term goal of my research is to study the mammalian retina as a model for the central nervous system (CNS) -- to understand how it functions in physiological conditions, how it is formed, how it breaks down in pathological conditions, and how it can be repaired. I have focused on two research themes: 1) Photoreceptor structure, synapse, circuits, and development, 2) Hibernation and metabolic adaptations in the retina and beyond. As the first neuron of the visual system, photoreceptors are vital for photoreception and transmission of visual signals. I am particularly interested in cone photoreceptors, as they mediate our daylight vision with high resolution color information. Diseases affecting cone photoreceptors compromise visual functions in the central macular area of the human retina and are thus most detrimental to our vision. However, because cones are much less abundant compared to rods in most mammals, they are less well studied. We have used the ground squirrel (GS) as a model system to study cone vision, taking advantage of their unique cone-dominant retina. In particular, we have focused on short-wavelength sensitive cones (S-cones), which are not only essential for color vision, but are also an important origin of signals for biological rhythm, mood and cognitive functions, and the growth of the eye during development. We are studying critical cone synaptic structures – synaptic ribbons, the synaptic connections of S-cones, and the development of S-cones with regard to their specific connections. These works will provide knowledge of normal retinal development and function, which can also be extended to the rest of CNS; for example, the mechanisms of synaptic targeting during development. In addition, such knowledge will benefit the development of optimal therapeutic strategies for regeneration and repair in cases of retinal degenerative disease. Many neurodegenerative diseases, including retinal diseases, are rooted in metabolic stress in neurons and/or glial cells. Using the same GS model, we aim to learn from this hibernating mammal, which possesses an amazing capability to adapt to the extreme metabolic conditions during hibernation. By exploring the mechanisms of such adaptation, we hope to discover novel therapeutic tactics for neurodegenerative diseases.

We will start our talk with a short video of our research, illustrating methods (some old and new) and findings that have provided our current understanding of how visual capabilities develop in infancy and early childhood. However, our research poses some outstanding questions. We will briefly discuss three issues, which are linked by a common focus on the development of visual attentional processing: (1) How do recurrent cortical loops contribute to development? Cortical selectivity (e.g., to orientation, motion, and binocular disparity) develops in the early months of life. However, these systems are not purely feedforward but depend on parallel pathways, with recurrent feedback loops playing a critical role. The development of diverse networks, particularly for motion processing, may explain changes in dynamic responses and resolve developmental data obtained with different methodologies. One possible role for these loops is in top-down attentional control of visual processing. (2) Why do hyperopic infants become strabismic (cross-eyes)? Binocular interaction is a particularly sensitive area of development. Standard clinical accounts suppose that long-sighted (hyperopic) refractive errors require accommodative effort, putting stress on the accommodation-convergence link that leads to its breakdown and strabismus. Our large-scale population screening studies of 9-month infants question this: hyperopic infants are at higher risk of strabismus and impaired vision (amblyopia and impaired attention) but these hyperopic infants often under- rather than over-accommodate. This poor accommodation may reflect poor early attention processing, possibly a ‘soft sign’ of subtle cerebral dysfunction. (3) What do many neurodevelopmental disorders have in common? Despite similar cognitive demands, global motion perception is much more impaired than global static form across diverse neurodevelopmental disorders including Down and Williams Syndromes, Fragile-X, Autism, children with premature birth and infants with perinatal brain injury. These deficits in motion processing are associated with deficits in other dorsal stream functions such as visuo-motor co-ordination and attentional control, a cluster we have called ‘dorsal stream vulnerability’. However, our neuroimaging measures related to motion coherence in typically developing children suggest that the critical areas for individual differences in global motion sensitivity are not early motion-processing areas such as V5/MT, but downstream parietal and frontal areas for decision processes on motion signals. Although these brain networks may also underlie attentional and visuo-motor deficits , we still do not know when and how these deficits differ across different disorders and between individual children. Answering these questions provide necessary steps, not only increasing our scientific understanding of human visual brain development, but also in designing appropriate interventions to help each child achieve their full potential.