Subthalamic nucleus lesion reverses motor abnormalities and striatal glutamatergic overactivity in experimental parkinsonism.
Subthalamic nucleus (STN) is a target of choice for the neurosurgical treatment of Parkinson's disease (PD). The therapeutic effect of STN lesion in PD is classically ascribed to the rescue of physiological activity in the output structures of the basal ganglia, and little is known about the possible involvement of the striatum. In the present study, therefore, we electrophysiologically recorded in vitro single striatal neurons of DA-depleted rats unilaterally lesioned by 6-hydroxydopamine, treated or not with therapeutic doses of levodopa (l-DOPA), or with a consecutive ipsilateral STN lesion. We show that the beneficial motor effects produced in parkinsonian rats by STN lesion or l-DOPA therapy were paralleled by the normalization of overactive frequency and amplitude of striatal glutamate-mediated spontaneous excitatory postsynaptic currents (sEPSCs). Since neither l-DOPA treatment nor STN lesion affected sEPSCs kinetic properties, the reversal of these abnormalities in striatal excitatory synaptic transmission can be attributable to the normalization of glutamate release.
Centonze
D
D
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. centonze@uniroma2.it
Gubellini
P
P
Rossi
S
S
Picconi
B
B
Pisani
A
A
Bernardi
G
G
Calabresi
P
P
Baunez
C
C
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000473:pathology / Q000502:physiology*; D003714:Denervation; D018698:Glutamic Acid / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D020531:Subthalamic Nucleus / Q000473:pathology / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000978:Antiparkinson Agents; D013565:Sympatholytics; D018698:Glutamic Acid; D007980:Levodopa; D016627:Oxidopamine