Thalamic neuronal activity in dopamine-depleted primates: evidence for a loss of functional segregation within basal ganglia circuits.
Different analyses of neuronal activity in primate models of Parkinson's disease (PD) have resulted in two different views on the effects of dopamine depletion. The first is based on the higher firing rate and bursty firing pattern, and assumes that dopamine depletion results in a hyperactivity of basal ganglia (BG) output structures. The second is based on the less-specific responses to passive joint manipulation and the excessive correlations between neuronal discharges, and assumes that dopamine depletion results in a loss of functional segregation in cortico-BG circuits. The aim of the present study was to test out the predictions of these two different views on thalamic neuronal activity. Three male vervet monkeys (Cercopithecus aethiops) were progressively intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal activities were characterized using standard analyses (firing rates and patterns, receptive fields, and cross-correlations) and compared between the normal, asymptomatic (before the stabilization of motor symptoms), and parkinsonian (with persistent akinesia and rigidity) stages of MPTP intoxication. The pallidonigral thalamus (receiving projections from the BG) was characterized in both the asymptomatic and parkinsonian states by (1) an unchanged firing rate and pattern and (2) a proliferation of nonspecific neurons and correlated pairs. In contrast, the cerebellar thalamus (receiving projections from the cerebellum), was characterized by no change (asymptomatic state) or minor changes (symptomatic state). Thus the major dysfunction after dopamine depletion appeared to be the loss of functional segregation within cortico-BG circuits, which could also be at the heart of parkinsonian pathophysiology.
Pessiglione
Mathias
M
Laboratoire de Neurologie et Thérapeutique Expérimentale, Institut National de la Santé et de la Recherche Médicale Unité 679, Hôpital de la Salpêtrière, 75651 Paris, France.
Guehl
Dominique
D
Rolland
Anne-Sophie
AS
François
Chantal
C
Hirsch
Etienne C
EC
Féger
Jean
J
Tremblay
Léon
L
D000200:Action Potentials; D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology*; D015415:Biomarkers; D002522:Chlorocebus aethiops; D004298:Dopamine / Q000172:deficiency*; D004567:Electrodes, Implanted; D004576:Electromyography; D020267:MPTP Poisoning / Q000503:physiopathology*; D008297:Male; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D013788:Thalamus / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine