Organization, Function and Development of Mammalian Visual System

II. Mouse Superior Colliculus:

The superior colliculus (SC), or optic tectum in lower vertebrates, 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 70% 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, 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 thus holds great promise for understanding visual transformation and its underlying circuit mechanisms.

I. Critical Period Plasticity:

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. One of the best studied examples of critical period plasticity is ocular dominance plasticity in the visual cortex, where cortical neurons lose their responsiveness to the deprived eye following monocular deprivation during a critical period in early postnatal development. Although decades of studies of ocular dominance plasticity and its critical period have provided important insights into experience-dependent neural development and human amblyopia (“lazy eye”), a fundamental question was still unanswered: what purpose does the critical period serve during normal development when inputs from the two eyes are intact?

A few years ago, we directly addressed this question in the mouse visual cortex. We reasoned that cortical neurons, which are the first stage that receives inputs from both eyes, must integrate the two streams of information carried by eye-specific inputs to achieve coherent binocular perception. Therefore, it is possible that normal visual experience during the critical period drives the binocular matching of orientation tuning, the most salient feature of cortical response properties. We carried out a series of physiological experiments and in fact proved this hypothesis (Wang B-S, Sarnaik and Cang, 2010). We found that individual cortical neurons prefer quite different orientations through the two eyes at the onset of the critical period, and this mismatch decreases and reaches adult levels by the end of the critical period (Fig. 1). Importantly, monocular 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.

Together, in this original study, we revealed a physiological role for critical period plasticity during normal development. As most studies were focused on changes induced by visual deprivation, our study represents a major paradigm shift and opens new venues of research on visual system development.

In the past few years, we have performed a series of studies to establish the mouse SC as a model for understanding visual system function and development. These include (1) using intrinsic optical imaging and computational approaches to examine the development of functional maps in the SC (Cang et al., 2008; Grimbert and Cang, 2012); (2) using microstimulation to reveal eye movement maps in the mouse SC (Wang et al., 2015); (3) using single-unit recording to characterize visual receptive field properties in the SC of wild type (Wang et al., 2010) and of various transgenic mice that have defects in development and/or retinal functions (Wang et al., 2009; Liu et al., 2014; Sarnaik et al., 2014);  (4) using optogenetics to determine the effect of cortical inputs on collicular responses in awake mice (Zhao et al., 2014); and (5) using 2-photon imaging to reveal a highly specialized lamina in the most superficial SC for movement direction (Inayat, Barchini, et al., 2015, Fig. 2). Together, these discoveries have provided important foundations for our ongoing studies to investigate the circuit and developmental mechanisms of visual transformation and sensorimotor integration in mice.