title: Effects of subthalamic nucleus lesions and stimulation upon corticostriatal afferents in the 6-hydroxydopamine-lesioned rat.
abstract: Abnormalities of striatal glutamate neurotransmission may play a role in the pathophysiology of Parkinson's disease and may respond to neurosurgical interventions, specifically stimulation or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate. Corticostriatal terminals can be distinguished within the striatum at the electron microscopic level as their synaptic vesicles contain the vesicular glutamate transporter, VGLUT1. The majority of terminals which are immunolabeled for glutamate but are not VGLUT1 positive are likely to be thalamostriatal afferents. We compared the effects of short term, high frequency, STN stimulation and lesioning in 6-hydroxydopamine (6OHDA)-lesioned rats upon striatal terminals immunolabeled for both presynaptic glutamate and VGLUT1. 6OHDA lesions resulted in a small but significant increase in the proportions of VGLUT1-labeled terminals making synapses on dendritic shafts rather than spines. STN stimulation for one hour, but not STN lesions, increased the proportion of synapses upon spines. The density of presynaptic glutamate immuno-gold labeling was unchanged in both VGLUT1-labeled and -unlabeled terminals in 6OHDA-lesioned rats compared to controls. Rats with 6OHDA lesions+STN stimulation showed a decrease in nerve terminal glutamate immuno-gold labeling in both VGLUT1-labeled and -unlabeled terminals. STN lesions resulted in a significant decrease in the density of presynaptic immuno-gold-labeled glutamate only in VGLUT1-labeled terminals. STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission.
authors.affiliation: Department of Neurology, James J Peters Veterans Affairs Medical Center, Bronx, New York, United States of America. ruth.walker@mssm.edu
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Walker
authors.forename: Cindy
authors.initials: C
authors.lastname: Moore
authors.forename: Georgia
authors.initials: G
authors.lastname: Davies
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Dirling
authors.forename: Rick J
authors.initials: RJ
authors.lastname: Koch
authors.forename: Charles K
authors.initials: CK
authors.lastname: Meshul
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D016627:Oxidopamine; D010300:Parkinson Disease / Q000503:physiopathology*; D051381:Rats; D020531:Subthalamic Nucleus / Q000473:pathology*; D009435:Synaptic Transmission / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D050598:Vesicular Glutamate Transport Protein 1; D016627:Oxidopamine