Functional properties and synaptic integration of genetically labelled dopaminergic neurons in intrastriatal grafts.
Författare
Summary, in English
ntrastriatal grafts of fetal ventral mesencephalic tissue, rich in dopaminergic neurons, can reverse symptoms in Parkinson's disease. For development of effective cell replacement therapy, other sources of dopaminergic neurons, e.g. derived from stem cells, are needed. However, the electrophysiological properties grafted cells need to have in order to induce substantial functional recovery are poorly defined. It has not been possible to prospectively identify and record from dopaminergic neurons in fetal transplants. Here we used transgenic mice expressing green fluorescent protein under control of the rat tyrosine hydroxylase promoter for whole-cell patch-clamp recordings of endogenous and grafted dopaminergic neurons. We transplanted ventral mesencephalic tissue from E12.5 transgenic mice into striatum of neonatal rats with or without lesions of the nigrostriatal dopamine system. The transplanted cells exhibited intrinsic electrophysiological properties typical of substantia nigra dopaminergic neurons, i.e. broad action potentials, inward rectifying currents with characteristic 'sag', and spontaneous action potentials. The grafted dopaminergic neurons also received functional excitatory and inhibitory synaptic inputs from the host brain, as shown by the presence of both spontaneous and stimulation-evoked excitatory and inhibitory postsynaptic currents. Occurrence of spontaneous excitatory and inhibitory currents was lower, and of spontaneous action potentials was higher, in neurons placed in the dopamine-depleted striatum than of those in the intact striatum. Our findings define specific electrophysiological characteristics of transplanted fetal dopaminergic neurons, and we provide the first direct evidence of functional synaptic integration of these neurons into host neural circuitries.
Avdelning/ar
- Wallenberg Neuroscience Centre, Lund
- Medicinska fakulteten
- Brain Repair and Imaging in Neural Systems (BRAINS)
- Neurobiologi
Publiceringsår
2005
Språk
Engelska
Sidor
2793-2799
Publikation/Tidskrift/Serie
European Journal of Neuroscience
Volym
21
Issue
10
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Wiley-Blackwell
Ämne
- Neurosciences
Nyckelord
- rats
- Parkinson's disease
- electrophysiology
- dopaminergic neurons
- stem cells
- transplantation
Status
Published
Forskningsgrupp
- Brain Repair and Imaging in Neural Systems (BRAINS)
- Neurobiology
ISBN/ISSN/Övrigt
- ISSN: 1460-9568