Motor injuries, such as stroke and spinal-cord injury, represent a significant public health burden, but often lack both cures and effective methods of symptom management. This has produced an urgent need for development of therapies that promote strengthening of injured neuronal pathways for restoration of critical functions, such as movement or sensation. Mechanisms that may induce synaptic plasticity are promising in their potential to augment weakened or injured pathways in the brain. This project aims to explore two such promising paradigms, targeted delivery of neuromodulators and closed-loop electrical stimulation, for potentiating cortical connections in a behaving macaque monkey. In the first experiment, I will be delivering a plasticity-enhancing neuromodulator, brain-derived neurotrophic factor (BDNF), to neurons in the motor cortex that fire in association with a wrist target-tracking motor task. BDNF has been shown to promote plasticity through inducing long-term potentiation, neuronal growth, axonal regeneration and re-myelination, and dendrite branching. Electrodes implanted at these sites will allow us to deliver stimulation to synaptically activate neurons to fire and test the strength of cortical connections, both in the presence and absence of BDNF, while the monkey performs the task. In the second experiment, I will explore an electrical-conditioning protocol to produce bidirectional spike-timing dependent plasticity in the same monkey. This will be achieved through paired intracortical microstimulation of two sites in the motor cortex, separated by a delay to produce synaptic changes. In both experiments, I will assess the effect of our intervention by measuring changes in the size and area of stimulation-evoked responses. We hypothesize that our interventions will result in significant potentiation of cortical connections. These results will inform how BDNF and electrical conditioning can modulate synaptic plasticity and strengthen neuronal connections.