Longitudinal optogenetic mapping reveals enhanced motor control by the contralesional cortex after traumatic brain injury in mice

Traumatic brain injury (TBI) is a significant cause of human disability, and understanding its spontaneous recovery pattern after injury is critical for potential treatments. However, studies on the function of the contralesional cortex after TBI have mostly focused on acute-phase changes, and long-term dynamic changes in the control of the affected limb by the contralesional cortex are less understood. To unravel long-term adaptations in the contralesional cortex, we developed a mouse model of TBI and used longitudinal optogenetic motor mapping to observe the function of contralesional corticospinal neurons (CSNs) projecting to the unilateral seventh cervical (C7) segment of the spinal cord. We injected a retrograde adeno-associated virus (AAV) expressing channelrhodopsin-2 to optogenetically stimulate and map the functional connections of the motor-sensory cortex. We validated the effectiveness of transcranial optogenetic stimulation for functional mapping and observed a general increase in the control of the affected limb by the contralesional cortex over time. Using retrograde labeling techniques, we showed that TBI does not affect the distribution of C7-CSNs but alters their function, and the labeled CSNs are concentrated in the caudal and rostral forelimb areas. Our findings provide new insights into harnessing contralesional cortical plasticity to improve treatment for affected limbs. This study sheds light on the long-term adaptations in the contralesional cortex after TBI, paving the way for potential clinical applications of optogenetic stimulation to improve motor control and rehabilitation outcomes.