Development and circuit Architecture of the Early Visual System
How does the circuitry of the early visual system support vision? Decades of effort, including work from our group, has revealed a part of the story. It begins in the retina, whose unique circuits process incoming images in parallel --each encodes a unique feature such as edges or motion and sends this report to the brain along the optic nerve. But what happens next is less clear, when downstream circuits synthesize this retinal feature report with internal states (ie:arousal, vigilance) to form channels of visual information that guide behavior.
We investigate this issue in the lateral geniculate nucleus of the thalamus (LGN). Although LGN is the only direct link between retina and cortex, its circuits receive most of their synaptic input from the brain. Could LGN be an important site at which visual and internal states combine ? Could LGN circuits represent an early site at which visual channels arise? How do LGN circuits assemble?
We investigate these issues by leveraging our extensive retinal circuit expertise which lets us mark, monitor, and manipulate incoming retinal inputs to LGN. We combine this expertise with cutting edge two-photon imaging methods and transsynaptic-tracing tools to see how LGN transforms and delivers these signals to the visual cortex and see how this transformation changes across development and when we genetically perturb different internal inputs to LGN.
Attention and Modulation of Visual processing
Every moment, an invisible mental spotlight roams the visual scene to enhance detection of stimuli most relevant for the task at hand. This spotlight is a fundamental cognitive ability called attention, and despite decades of study, its circuit-level mechanisms remain elusive.
Where does the attention signal arise within the brain? How does this signal interact with the circuits of the visual pathway? How does this interaction enhance the brain's representation of salient visual locations or features? To investigate these issues, we have developed a novel behavioral task that allows us to resolve where and what a mouse attends with high spatial and temporal precision. By combining this task with mesoscale and two-photon imaging of activity within large population of neurons across the visual pathway and cortical hierarchy, we aim to define where attention arises and what its neural substrates are. By combining these methods with new tools to perturb neural activity in vivo we will define the circuitry that implements attentional selection and enhancement.
Circuit Dysfunction and Disease
Sight is a vital to our health and quality of life. According to the WHO, over 2.2 billion people have a vision impairment, ranging from disorders of lens/cornea, through degenerative loss of neurons from the retina, or damage/death of neurons located deeper in the visual pathway. Beyond traditional vision loss, visual processing dysfunction affects an even larger population and is an early and key diagnostic feature of autism spectrum disorder (ASD). Visual processing deficits appear early in ASD and their severity predicts the appearance of later social, verbal, and cognitive deficits.
We are actively translating basic understanding gained from our research to address these issues. Specifically, we are pursuing collaborative projects related to vision loss in the retina and independent projects related to attentional deficits in mouse models of ASD. By building upon our long-standing expertise in neural development and new insights into higher visual circuit function, we aim to define new disease-causing mechanisms and therapeutic strategies to address these serious illnesses.