Role of experience, training, and plasticity in the functional efficacy of striatal transplants

Cell-based treatments of neurodegenerative diseases have been tested clinically with partial success. In the context of Huntington's disease (HD), experimental studies show that the grafted embryonic striatal cells survive, integrate within the host brain, and reverse some functional deficits. Importantly, once transplanted, the grafted striatal neurons retain a significant level of cellular, morphological, and functional plasticity which allows the experimental modification of their character through the manipulation of environmental cues or learning protocols. Using embryonic striatal grafts in the rodent model of HD as the principal example, this chapter summarizes seminal experiments that demonstrate that environmental factors, training, and activity can tap into mechanisms that influence the development of the grafted cells and can change the profile of graft-mediated behavioral recovery. Although currently there is limited understanding of the biological rationale behind the recovery, we put forward experimental data indicating that striatal grafts can express experience-dependent physiological plasticity at the synaptic as well as at the systemic functional level.