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Optical dissection of cortical motor circuits

Final Report Summary - OPTOMOT (Optical dissection of cortical motor circuits)

Frontal cortex plays a key role in learning and orchestrating fine voluntary movements, which dominate many aspects of our daily lives. From tying our shoes to manipulating our iphones, we rely on these circuits without noticing. Despite decades of research, considerable controversy remains over the functional organization of this forebrain area and its role in goal directed action. The goal of this ERC funded project termed OPTOMOT, was to dissect cortical circuits in the mouse with innovative approaches. For this purpose we first developed an “optical Brain-Machine Interface” (oBMI). The oBMI allowed us to optically read out and decode the activity of any arbitrary set of neurons in real time and then to use this information to manipulate the activity of the identified neurons in hypothesis driven ways, thereby establishing causal links between neuronal activity and behavior. First, we were able to show that mice can rapidly learn to voluntarily control neuronal activity based on artificial, microstimulation based feedback. They are thus able to integrate information from this artificial channel as if it was natural sensory feedback. Furthermore this study revealed that the learned activity is highly specific to the trained neurons and does not affect the neighbors in the close vicinity. In a second set of studies we investigated the role of motor cortex in a novel forelimb related task for mice. We used optogenetic inactivation to determine at what moment these cortical circuits are necessary during goal directed action. This study revealed that motor cortex, as well as neighboring premotor areas are intimately involved with the planning and execution of forelimb movements. Finally, using a novel, multi directional reaching task for mice we were able to show that the neuronal activity in the motor cortex was strongly related to the directional information. This novel task promises to open new doors towards the study of motor control in rodents. In parallel, this research aim has also revealed several serendipitous, yet profound findings related to the perception of high frequency vibrations in the forelimbs and to cortical activity dynamics during different sleep states. In summary, the OPTOMOT project has been very successful and has resulted in 7 peer reviewed scientific publications over this 5 year period.