JANUS · Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses

In an ever-changing natural world, animals must constantly adapt their behavior by extracting relevant information from the environment in a context-dependent manner. This is a complex task because the relevance of sensory stimuli rapidly changes according to the animal’s internal states, evidence, attention and goals. In the brain, neuromodulatory systems are thought to encode environmental and internal signals, such as novelty, reward, effort and risk, providing critical input to ensure appropriate action selection. However, classically, neuroscientists have opted to study sensorimotor transformations as a reflex arc, largely ignoring complex modulatory contributions due to their experimental inaccessibility. In this proposal, I will explore the neuromodulatory strategies used by the brain to tailor sensorimotor computations according to the immediate needs of the animal.A key node for sensorimotor transformation and spatial attention is the Superior Colliculus (SC). The SC is also a neuromodulatory hub, where retinal streams converge with highly diverse and functionally mysterious neuromodulatory inputs. Here, I will take advantage of the SC’s role as a gatekeeper in sensory processing and behavioral control to unravel the multiplexed logic and function of neuromodulation. To do so, I will first quantitatively describe SC’s visual and non-visual dynamics on a moment-by-moment basis and define their interactions. Next, I will determine the properties, orchestration and influence of SC’s neuromodulatory inputs on sensory processing, goal-directed behaviors and spatial attention. Finally, I will describe the role of neuromodulation mechanistically by developing a novel functional connectomics approach and mapping circuit motif changes. Given the implication of neuromodulation in brain disorders, this work will shed light on the tight orchestration of neuromodulation that ensures appropriate or abnormal selection of actions, according to the animal’s immediate needs