Embryonic striatal grafts restore bi-directional synaptic plasticity in a rodent model of Huntington's disease.
Embryonic striatal grafts integrate with the host striatal circuitry, forming anatomically appropriate connections capable of influencing host behaviour. In addition, striatal grafts can influence host behaviour via a variety of non-specific, trophic and pharmacological mechanisms; however, direct evidence that recovery is dependent on circuit reconstruction is lacking. Recent studies suggest that striatal grafts alleviate simple motor deficits, and also that learning of complex motor skills and habits can also be restored. However, although the data suggest that such 're-learning' requires integration of the graft into the host striatal circuitry, little evidence exists to demonstrate that such integration includes functional synaptic connections. Here we demonstrate that embryonic striatal grafts form functional connections with the host striatal circuitry, capable of restoring stable synaptic transmission, within an excitotoxic lesion model of Huntington's disease. Furthermore, such 'functional integration' of the striatal graft enables the expression of host-graft bi-directional synaptic plasticity, similar to the normal cortico-striatal circuit. These results indicate that striatal grafts express synaptic correlates of learning, and thereby provide direct evidence of functional neuronal circuit repair, an essential component of 'functional integration'.
Graduate School of Medicine, University of Wollongong, NSW, Australia. davidmj@uow.edu.au
David
D
Mazzocchi-Jones
Máté
M
Döbrössy
Stephen B
SB
Dunnett
D000818:Animals; D001703:Biophysics; D016009:Chi-Square Distribution; D003342:Corpus Striatum / Q000502:physiology* / Q000637:transplantation; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006816:Huntington Disease / Q000601:surgery*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D016378:Tissue Transplantation / Q000379:methods*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine