Organization, Function and Development of Mammalian Visual System
The overall goal of our research is to study the neural basis of vision: how neurons in the brain respond to visual stimuli and lead to visually-guided behaviors; what neural circuits give rise to such function properties; and how these circuits are established during development. We use mice and tree shrews as models, and take an integrative approach that combines in vivo physiology, two-photon calcium imaging, genetics, genomics, behavioral, and computational techniques. Below are some of our ongoing studies. Contact us at (cang at virginia.edu) if you are interested in joining us.
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Critical Period Plasticity and Binocular Vision
Unlike hard-wired electronic circuits, neural circuits in the brain can already perform certain functions before they are fully assembled. The activity patterns that the developing neural circuits experience while performing such functions in turn shape the circuit connections in an experience-dependent manner. These experience-dependent processes give the brain the ability to adapt to various external environments and to individual differences, allowing, for example, Chinese children growing up in the U.S. to speak English as native speakers. Neural circuits are most sensitive to sensory manipulation – that is, the brain is most “plastic” – during specific time windows in early life, and this plasticity then declines with age. These time windows are often referred to as “critical periods”, because they are not only windows of opportunity, but also of vulnerability, as failing to receive appropriate experience during these periods leads to abnormal circuit formation that is difficult to repair later in life.
In studying critical period, we discovered that the heightened plasticity in the visual system drives the matching of cortical orientation preference between the two eyes during normal development (Wang et al., 2010). Importantly, visual deprivation during this time window blocks binocular matching, and the impaired matching cannot spontaneously recover with subsequent experience, thus closely mimicking the condition of amblyopia in children. Over the years, we have revealed the precise time course of binocular matching (Wang et al., 2013), studied its receptive field basis (Sarnaik et al., 2014), dissected the contributions of thalamocortical and intracortical circuits (Gu and Cang, 2016), and followed its recovery using chronic imaging (Levine et al., 2017). In addition, we have studied the cellular mechanism of binocular integration in mouse V1 (Zhao et al., 2013b), and also revealed the functional significance of critical period timing in establishing normal binocularity (Krishnan et al., 2015; Wang et al., 2013). These experiments have revealed new directions of research for investigating the circuit mechanisms underlying binocular matching, particularly regarding cortical and thalamic contributions. We are currently pursing these directions in both mice and tree shrews.
The superior colliculus (SC), or optic tectum, is a midbrain structure involved in multimodal sensorimotor integration, spatial attention, and orientating movements. It is an evolutionarily conserved structure that receives direct retinal input in all known taxa of vertebrates and it was the most sophisticated visual center until the neocortex emerged in mammals. Even in mice, a mammalian species that has become a useful model in vision research in recent years, more than 85% of RGCs project to the SC. With the advances in mouse genetics, it is now possible to identify subtypes of neurons within a given brain structure, to trace synaptic connectivity, and to manipulate gene expression and neuronal activity in a spatially and temporally controlled manner. These advances, together with the recent development of 2-photon Ca2+ imaging and large-scale electrophysiology recording , have enabled rapid progress in functional studies of the mouse visual system. Given its clear importance in visually-guided behaviors and the available genetic tools, the mouse SC holds great promise for understanding visual transformation and its underlying circuit mechanisms.
In the past ~10 years, we have performed a series of studies to help establish the mouse SC as a model in vision research. We made a number of novel discoveries in these studies, such as (1) diverse response properties in the mouse SGS, including direction and orientation selectivity (Wang et al., 2010); (2) a depth-specific organization of direction selectivity in the SGS (Inayat et al., 2015) (3) a retinal origin of SC direction selectivity (Shi et al., 2017); (4) eye movement maps in deep layers of the SC (Wang et al., 2015); (5) a gain control of SC responses by visual cortical input (Zhao et al., 2014); and (6) bidirectional encoding of motion contrast in the SC (Barchini et al., 2018). We are currently focusing on understanding cell-type-specific visual processing in the SC and its modulation by external and internal states.
We have recently started using tree shrews in our research. Despite the name, tree shrews are not “true” shrews. They are in fact small euarchontoglire mammals that are closely related to primates. Tree shrews have a long history in vision research, thanks to their highly developed visual system and dependence on vision. The tree shrew visual system shares various features with primates. Furthermore, tree shrews have a short reproductive cycle, ~45 days in gestation and ~4 months from birth to sexual maturity, making them an excellent choice for developmental studies. We are currently performing functional studies of both visual cortex and superior colliculus in the tree shrew, as well as behavioral studies such as perceptual decision-making in this species.
