Alterations in rat striatal glutamate synapses following a lesion of the cortico- and/or nigrostriatal pathway

Exp Neurol. 2000 Sep;165(1):191-206. doi: 10.1006/exnr.2000.7467.

Abstract

Ultrastructural changes within the ipsilateral dorsolateral striatum were investigated 1 month following a unilateral ablation of the rat frontal cortex (CTX), removing corticostriatal input, or injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), into the substantia nigra pars compacta, removing nigrostriatal input. In addition, a combined ipsilateral cortical and 6-OHDA lesion (CTX/6-OHDA) was carried out. We find that following a CTX, 6-OHDA, or CTX/6-OHDA lesion, there was a significant decrease in the density of striatal nerve terminal glutamate immunoreactivity compared to the control group. There was also a significant increase in all three lesion groups in the mean percentage of asymmetrical synapses associated with a perforated postsynaptic density. There was a large increase within the CTX/6-OHDA-lesioned group and a smaller but still significant increase in the CTX-lesioned group in the percentage of terminals or boutons with multiple synaptic contacts (i.e., multiple synaptic boutons, MSBs), compared to either the 6-OHDA or the control group. There was no change in any of these measurements within the contralateral striatum. There was a significant decrease in the number of apomorphine-induced contralateral rotations in the CTX/6-OHDA versus the 6-OHDA-lesioned group. Animals receiving just the single CTX or 6-OHDA lesion recovered in motor function compared to the control group as measured by the Rotorod test, while the CTX/6-ODA-lesioned group recovered to less than 50% of the control level. The data suggest that following a CTX and/or 6-OHDA lesion, there is an increase in striatal glutamatergic function. The large increase in the percentage of MSBs in the combined lesion group suggests that dopamine or other factors released by the dopamine terminals assist in regulating synapse formation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Diseases / metabolism
  • Brain Diseases / pathology*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology*
  • Glutamic Acid / metabolism*
  • Immunohistochemistry
  • Male
  • Microscopy, Electron
  • Motor Activity
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Presynaptic Terminals / ultrastructure
  • Rats
  • Rats, Inbred F344
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology*
  • Synapses / metabolism
  • Synapses / ultrastructure*

Substances

  • Glutamic Acid