Project Summary: Memory Formation in Motor Cortex Memories both impart identity and provide competence in our daily activities. Our motor memories are crucial for interacting with the world around us: The loss of dexterity can be a particularly debilitating consequence of stroke. Despite their importance, we still know very little about how the brain forms and stores the memories of our motor abilities. This research project endeavors to understand the role of the primary motor cortex (M1) in the inception and retention of motor memories. Since it is the organized activity of populations of neurons that control our movements, we seek signatures of memories in how neural populations change their activity after a learning experience. We adopt a powerful tool for studying learning in the motor cortex – brain computer interfaces (BCIs). In a BCI, the user generates patterns of neural activity which drive the movement of an external device, such as a cursor on a computer screen. Decades of prior research have demonstrated the validity of BCIs as a tool to study learning in the motor system, and here we leverage that prior research to study motor memories. Our three Specific Aims address different aspects of motor memories: First, we examine the link between signatures of a memory in M1 population activity and improved behavioral performance following learning. Second, we examine how learning something new is influenced by the memory of a previous learning experience, and conversely, how new learning can impact the neural encoding of an existing motor memory. Third, we examine the consolidation of motor memories, to see what changes in the days after a learning experience. Our BCI paradigm offers powerful advantages for exploring these questions. This is because a BCI directly couples neural population activity to a behavior. This direct causal relationship makes it possible to see the appearance of a motor memory that is specific to and appropriate for the behavior that has been learned, and to track it over time. Also, because we use BCI systems in our basic-science studies, our findings have direct clinical relevance for the ongoing effort to improve BCIs so that they can restore dexterous and flexible motor control to individuals with paralysis.