TIME-DEPENDENT CHANGES IN STRIATAL GLUTAMATE SYNAPSES FOLLOWING A 6-HYDROXYDOPAMINE LESION

The goal of this study was to investigate changes in glutamatergic syn apses in the striatum of rats at two different time-points following a unilateral injection of 6-hydroxydopamine into the medial forebrain b undle. One month following this lesion of the nigrostriatal pathway, t here was an increase (70%) in the mean percentage of asymmetrical syna pses within the dorsolateral striatum containing a discontinuous, or p erforated, postsynaptic density, possibly suggesting an increase in gl utamatergic activity. This was correlated, in the same brain region, w ith a decrease (44%) in the density of glutamate immunoreactivity with in 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-f old) in the basal extracellular level of striatal glutamate, as measur ed by in vivo microdialysis. The density of GABA immunolabeling within symmetrical nerve terminals was increased (25%) at this one month tim e-period. Dopamine levels within the lesioned striatum were >99% deple ted. However, at three months, while an increase in the mean percentag e of striatal perforated synapses was maintained, a significant increa se (50%) in the density of striatal nerve terminal glutamate immunolab eling within all asymmetrical synapses and those associated with a per forated postsynaptic density was observed. This was correlated with a small, but significant, decrease (32%) in the basal extracellular leve l of striatal glutamate. The density of GABA immunolabeling within ner ve terminals associated with a symmetrical contact remained elevated a t this three month time-period, while striatal dopamine levels remaine d depleted. While the density of nerve terminal GABA immunolabeling re mained elevated at both the one and three month time-periods, there ap peared to be a differential effect on glutamatergic synapses. The in v ivo microdialysis data suggest that glutamate synapses were more activ e 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 s triatum following a 6-hydroxydopamine lesion that appear to be indepen dent of the level of striatal dopamine or GABA. We propose that change s in the activity of the thalamo-cortico-striatal pathway may help to explain the differential time-course change in striatal glutamatergic synaptic activity. (C) 1998 IBRO. Published by Elsevier Science Ltd.