The Journal of Neuroscience, June 1, 1998, 18(11):4133-4144
Regulation of the Nigrostriatal Pathway by Metabotropic Glutamate
Receptors during Development
Dietmar
Plenz and
Stephen T.
Kitai
University of Tennessee, College of Medicine, Department of Anatomy
and Neurobiology, Memphis, Tennessee 38163
Dopamine neurons in the substantia nigra heavily innervate the
striatum, making it the nucleus with the highest levels of dopamine in
the adult brain. The present study analyzes the time course and the
density of striatal innervation by nigral dopamine neurons and
characterizes the role of the neurotransmitter glutamate during the
development of the nigrostriatal pathway. For this purpose, organotypic
cultures containing the cortex, the striatum, and the substantia nigra
(triple cultures) were prepared from rat brains at postnatal day (PND)
0-2 and were cultured for up to 60 d in vitro
(DIV). Dopamine fibers and neurons were labeled using tyrosine
hydroxylase (TH) immunohistochemistry. Striatal TH-ir fiber density was
quantitatively analyzed using confocal laser scanning microscopy
(CLSM). In long-term triple cultures (44 ± 3 DIV), the striatal
dopamine fiber density was high and was weakly correlated with the
number of nigral dopamine neurons. The high striatal dopamine fiber
density mainly resulted from an enhanced ingrowth and ramification of
dopamine fibers from nigral neurons during 8-17 DIV. The metabotropic
glutamate receptor (mGluR) antagonist
L(+)-2-amino-3-phosphonopropionic acid (L-AP-3) selectively inhibited this dopaminergic innervation of the
striatum, whereas ionotropic GluR antagonists had no effect. The
L-AP-3-mediated inhibition was prevented by the mGluR
agonist
1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). The inhibition of the
striatal dopaminergic innervation by L-AP-3 was
further confirmed by anterograde tracing of the nigrostriatal
projection with Phaseolus vulgaris leucoagglutinin. These results indicate that glutamate, by acting on group I mGluRs, plays an important "trophic" role for the development of the
nigrostriatal dopamine pathway.
Key words:
development; substantia nigra; striatum; nigrostriatal
projection; cortex; metabotropic glutamate receptor; dopamine; neurotrophic factor; organotypic culture
Copyright © 1998 Society for Neuroscience 0270-6474/98/18114133-12$05.00/0
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