Functional analysis of fronto-striatal reconstruction by striatal grafts

Excitotoxic lesions of the neostriatum induce cognitive and motor deficits in experimental animals, and model both the neuropathology and symptoms of Huntington's disease. Striatal grafts implanted into the denervated striatum survive, differentiate into both striatal- and non-striatal like neurons, restore input and output connections of the damaged striatum, and alleviate both motor and cognitive impairments in experimental rats and monkeys. Several lines of evidence suggest that the functional recovery is mediated by the grafts providing a reconstruction of the cortico-striato-pallidal circuitries of the host forebrain, including functional mapping of circuitry by immediate early gene induction, push-pull perfusion, microdialysis, electrophysiology, the lack of efficacy of pharmacological treatments and the behavioural studies themselves. Detailed analysis of motor recovery in an operant lateralized choice reaction time test indicates that for optimal functional recovery the animals require specific retraining in the stimulus response associations lost by the lesions, which may have important implications for optimizing the functional efficacy of striatal grafts both in experimental models and clinical trials.