Combining Vision with Action one Synapse from the Eye

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One synapse away from the eye lies a fundamental brain structure, the superior colliculus, responsible for integrating sensory input, allocating attention to spatial locations, and generating orienting movements of the head and body to those locations. The inputs from the eye go to the superficial portion of the superior colliculus (sSC), which is thought to contain a mostly visual representation of the external world. Recent observations in our laboratory, however, suggest that sSC does much more than pure vision: its visual responses are strongly shaped by non-sensory signals. The proposed project will reveal how this key brain region combines visual signals with non-sensory signals reflecting brain and behavioral state, decision processes and motor actions. Further, it will help reveal the sources of non-sensory signals, and provide a simple model of the functional effects of this combination of visual and non-sensory signals, and of the underlying neural circuits. To achieve these goals, we will leverage novel neural imaging and behavioral techniques that we have developed in our laboratory. We will use two-photon imaging to record activity of hundreds of genetically identified neurons within the sSC of awake mice. The same technique will reveal the activity of the inputs to those neurons originating in the eye or in the cerebral cortex. These imaging measurements will be made while mice are passively viewing a stimulus or actively performing a visual task. Our first objective focuses on how sSC is affected by brain and behavioral state such as arousal and locomotion. We will image responses in sSC to a range of visual stimuli and relate them to the level of arousal, as reflected by pupil diameter, and to locomotion. Preliminary data indicate that these factors have an enormous effect on the responses of some cells and a negligible one on others. We will distinguish cell classes to map these effects onto the circuits of sSC. Our second objective focuses on how sSC is affected in interactive conditions where visual stimuli are used for specific decisions and actions. We will image different cell classes in the sSC while the animal performs a visual task requiring a goal-directed movement. We will relate responses to stimulus, performance, and action using simple correlation measures and a predictive model of neural responses. The data will characterize how the sSC combines visual signals with signals related to decision and action.Our third objective focuses on the sources and circuits that provide the sSC with non-sensory signals. The main visual inputs to sSC originate from the eye and from the cerebral cortex. To assess their role in providing visual and non-sensory signals, we will image the activity of their axon terminals in sSC and the activity of cortical neurons projecting to the sSC. We will then inactivate the cortex to reveal its effect on sSC. The results will characterize the signals that sSC inherits from the eye and from the cortex, and will indicate if the latter is necessary to explain the combination of visual and non-sensory signals seen in sSC. Results from all objectives will allow us to build simple functional and circuit models for the combination of visual and non-sensory signals in the sSC.These experiments have the potential to change the way we think about how the brain integrates sensory and non-sensory inputs, showing how neurons getting direct input from the eye combine visual signals with signals related to brain and behavioural state, decisions, and actions.Expanding our understanding of the function and circuitry of the superior colliculus will eventually enable us to simulate and replicate how this brain area transforms sensory input into commands that allocate attention and generate actions. It may also help to understand attentional deficits in disease and develop cures and therapies.