Large-Scale Dynamics in the Mouse Neocortex underlying Sensory Discrimination and Short-Term Memory

Abstract

Sensorimotor integration (SMI) is a fundamental process that allows for an advantageous interaction with the environment, in which key external stimuli are transformed into apt action. In mammals, SMI requires quick and synchronized activity across sensory, association and motor brain areas of the neocortex. In some situations, the key stimulus and its corresponding action are separated by a delay. In such scenario, behaviour-relevant information must be held in short-term memory (STM) until a cue signals the adequate context to transform it into action. This thesis aims to uncover key determinants of brain activity that underlie SMI with a STM component. The first chapter offers a general introduction to the work presented in this thesis. To understand the principles of SMI, I will follow an evolutionary approach. I will explain how during SMI information flows across sensory and association areas. I will also introduce STM and the neocortical areas involved in delay activity. Next, I will emphasize the different sensing and behavioural strategies that animals use to extract action-guiding information from the world. Finally, I will propose different behavioural paradigms to study SMI and STM. Once this foundation is laid, I will introduce the methodological approach of this thesis, in particular genetically-encoded calcium indicators and wide-field imaging. I will end this chapter by stating the specific aims of this thesis. The second chapter is a published manuscript in which I contributed during the first two years of my doctoral thesis work. We studied large-scale dynamics in mice trained to solve a tactile discrimination task with a STM component. We found that mice follow an active and/or passive strategy to solve this task, defined by the presence or absence of whole body movements during tactile stimulation. The movement strategy influenced ongoing brain activity, with higher and more widespread activity in active versus passive trials. Surprisingly, this influence continued into the STM period even in the absence of movements. Active trials elicited activity during the delay period in frontomedial secondary motor cortex. In contrast, passive trials were linked with activity in posterior lateral association areas (PLA). We found these areas to be necessary for task completion in a strategy-dependent manner