Understanding perceptual decision-making is a fundamental question in neuroscience. Anatomical studies demonstrate a hierarchy of cortical areas, with visual information (for example) flowing from primary visual to higher visual to association to motor regions. Complexity of interactions between these areas precludes the idea of a one-to-one assignment of function, especially for higher cortical areas. In the visual pathway, neural correlates of the sensory, memory and motor components of a perceptual decision, such as in a delayed response task, can be identified in a range of cortical areas. Addressing perceptual decision-making in a mechanistic way requires deciphering signatures of multiple cognitive components across multiple brain regions. We intend in this project to explore the signatures of and relationships between incoming sensory percepts, retention of sensory information in short-term memory, and choice of appropriate motor action in mice. This project requires new imaging techniques we have developed, which allow us to examine activity in multiple brain regions during performance of a learned task. These complex data sets require us to employ new statistical methods to analyze cell-type-specific and region-specific population activity patterns. Population responses are composed of the activity of many contributing neuron-neuron interactions. To carry this analysis through to the level of individual connections, we use retrograde tracers such as rabies virus to label connected pairs of cells, and subsequently image these connections intact. We plan to manipulate the activity of neurons across these inter-areal connections using optogenetic tools. These technologies give us a lever with which to manipulate different stages of the task, in order to isolate the regions and cell types involved in task completion and also the time course of their involvement.
[BRAIN Initiative project In collaboration with Emery Brown, Ian Wickersham and Kwanghun Chung]