Plasticity of synapses in the rat neostriatum after unilateral lesion of the nigrostriatal dopaminergic pathway.
In the 6-hydroxydopamine model of Parkinson's disease in the rat, there is a significant reduction in the number of dendritic spines on the principal projection neurons in the neostriatum, presumably attributable to loss of the nigrostriatal dopamine input. These spines invariably receive input from terminals forming asymmetric synapses that originate mainly from the cortex. The object of the present study was to determine the fate of those terminals after the loss of dendritic spines. Unbiased estimates of synaptic density and absolute numbers of synapses in a defined volume of the neostriatum were made using the "disector" and Cavalieri techniques. Numerical synaptic density of asymmetric synaptic contacts was 17% lower in the neostriatum deprived of dopamine innervation and, in absolute terms, there were 3 billion (19%) fewer contacts. The numerical density of a subpopulation of asymmetric contacts on dendritic spines that have complex or perforated synaptic specializations and normally make up 9% of the asymmetric population was 44% higher on the experimental side. Asymmetric synapses were found to be enriched in glutamate using postembedding immunogold labeling. The present observations demonstrate that the loss of spines previously reported after 6-hydroxydopamine lesions is accompanied by a loss of asymmetric synapses rather than by the movement of synapses from spines to other postsynaptic targets. The study also demonstrates that there is an increase in complex synaptic interactions that have been implicated in synaptic plasticity in other regions of the CNS after experimental manipulations.
Ingham
C A
CA
University of Edinburgh Centre for Neuroscience and Department of Preclinical Veterinary Sciences, University of Edinburgh, Summerhall, Edinburgh, United Kingdom EH9 1QH.
Hood
S H
SH
Taggart
P
P
Arbuthnott
G W
GW
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004298:Dopamine / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009473:Neuronal Plasticity / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D016627:Oxidopamine; D004298:Dopamine