Functional Analysis of Fronto–Striatal Reconstruction by Striatal Grafts

  1. Derek J. Chadwick Organizer and
  2. Jamie A. Goode
  1. Stephen B. Dunnett

Published Online: 7 OCT 2008

DOI: 10.1002/0470870834.ch3

Neural Transplantation in Neurodegenerative Disease: Current Status and New Directions: Novartis Foundation Symposium 231

Neural Transplantation in Neurodegenerative Disease: Current Status and New Directions: Novartis Foundation Symposium 231

How to Cite

Dunnett, S. B. (2008) Functional Analysis of Fronto–Striatal Reconstruction by Striatal Grafts, in Neural Transplantation in Neurodegenerative Disease: Current Status and New Directions: Novartis Foundation Symposium 231 (eds D. J. Chadwick and J. A. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470870834.ch3

Author Information

  1. Centre for Brain Repair and Department of Experimental Psychology, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK

  1. Cardiff School of Biosciences, Cardiff University, Museum Avenue, PO Box 911, Cardiff CF10 3US, UK

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 23 OCT 2000

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780471492467

Online ISBN: 9780470870839

SEARCH

Summary

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.