Optical sensory and motor mapping of mouse dorsal cortex

Throughout species, including mice and humans, we all have to make decisions to fulfill our fundamentals needs: eat, drink, explore, communicate, reproduce... To make those decisions, we have to collect informations from the surrounding world and to process them with our nervous system. The neocortex is the most distinctive feature of the brain as it is the substrate of high cognitive functions. One commonly used model to study the brain is the mouse. Mice can be genetically modified to express fluorescent reporters, or optogenetic actuators in their neurons. The questions I ask in this thesis are where and when specific sensory information is processed in the mouse cortex, and where and when these signals are integrated to generate to a motor command. First, I developed a protocol to get reliable sensory maps from wide-field optical intrinsic signal imaging. Mice undergo a surgical procedure to get a relatively transparent view of the left dorsal cortex. Then I sequentially repetitively stimulated different parts of the body of anesthetized mice to map the cortical sensory representation of each stimulated organ. I also successfully imaged optogenetically evoked responses by combining optogenetic experiment with wide-field optical intrinsic signal imaging. Second, I found the coordinates of the tongue/jaw primary sensory cortex tjS1 and of the tongue/jaw primary motor cortex tjM1. While I was mechanically stimulating tongue and jaw in anesthetized Thy1-GCaMP6f mice, I imaged the calcium signals evoked in the left cortical hemisphere with a wide-field fluorescence macroscope. Third, I recorded cortical activity of behaving mice performing a 2-whisker discrimination task with the wide-field calcium imaging technique. There was a large difference between hit and miss trials. The amplitude of the responses in S1, S2, M1 and M2 were decreasing over the days of training. The earliest difference between hit and miss response occurred in S1 and S2 after 100 ms. Then the signals converged toward M2 where the amplitude of the response was amplified to lead to a lick command. Finally, I optogenetically stimulated the cortex of awake mice and I measured the evoked whisker movements to obtain whisker motor maps. I found that almost the entire cortex can evoke whisker movement. The earliest evoked movement occurred when S1 was stimulated, the contralateral whisker had a prolonged retraction. Then the ipsilateral whisker started large rhythmic protractions. When M1 was stimulated, it triggered the most protracted whisker movement of rhythmic protractions. The largest oscillating protraction was observed when the parietal association area (PtA) was stimulated. These data suggest that neuronal information needed to perform even simple tasks requires distributed cortical areas to process sensory inputs, like passive whisker deflection or optogenetic stimulation, and in return generate motor outputs, like licking or whisking. Future experiments must investigate the complex neuronal circuits connecting specific cell- types in various cortical regions using wide-field calcium imaging and combine it with optogenetic manipulations of this network at specific times and brain regions.