Time-dependent changes in striatal glutamate synapses following a 6-hydroxydopamine lesion.
The goal of this study was to investigate changes in glutamatergic synapses in the striatum of rats at two different time-points following a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. One month following this lesion of the nigrostriatal pathway, there was an increase (70%) in the mean percentage of asymmetrical synapses within the dorsolateral striatum containing a discontinuous, or perforated, postsynaptic density, possibly suggesting an increase in glutamatergic activity. This was correlated, in the same brain region, with a decrease (44%) in the density of glutamate immunoreactivity within nerve terminals associated with all asymmetrical synapses and also with those terminals associated with a perforated postsynaptic density. These morphological changes were consistent with an increase (>two-fold) in the basal extracellular level of striatal glutamate, as measured by in vivo microdialysis. The density of GABA immunolabeling within symmetrical nerve terminals was increased (25%) at this one month time-period. Dopamine levels within the lesioned striatum were >99% depleted. However, at three months, while an increase in the mean percentage of striatal perforated synapses was maintained, a significant increase (50%) in the density of striatal nerve terminal glutamate immunolabeling within all asymmetrical synapses and those associated with a perforated postsynaptic density was observed. This was correlated with a small, but significant, decrease (32%) in the basal extracellular level of striatal glutamate. The density of GABA immunolabeling within nerve terminals associated with a symmetrical contact remained elevated at this three month time-period, while striatal dopamine levels remained depleted. While the density of nerve terminal GABA immunolabeling remained elevated at both the one and three month time-periods, there appeared to be a differential effect on glutamatergic synapses. The in vivo microdialysis data suggest that glutamate synapses were more active at a basal level at one month and become less active compared to the control group at the three month time-period. These data suggest that there are compensatory changes in glutamatergic synapses within the striatum following a 6-hydroxydopamine lesion that appear to be independent of the level of striatal dopamine or GABA. We propose that changes in the activity of the thalamo-cortico-striatal pathway may help to explain the differential time-course change in striatal glutamatergic synaptic activity.
Meshul
C K
CK
V.A. Medical Center, Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland 97201, USA.
Emre
N
N
Nakamura
C M
CM
Allen
C
C
Donohue
M K
MK
Buckman
J F
JF
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D007839:Functional Laterality; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity; D011188:Potassium / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors
D018698:Glutamic Acid; D016627:Oxidopamine; D011188:Potassium