Re-evaluation of the functional anatomy of the basal ganglia in normal and Parkinsonian states.
In the late 1980s, a functional and anatomical model of basal ganglia organization was proposed in order to explain the clinical syndrome of Parkinson's disease. According to this model, the pathological overactivity observed in the subthalamic nucleus and the output station of the basal ganglia plays a crucial role in the pathophysiology of the motor signs of Parkinson's disease. The hyperactivity of subthalamic neurons in Parkinsonism is viewed as a direct consequence of a pathological hypoactivity of the external segment of the pallidum. This article reviews recent data from different experimental approaches that challenge the established model of basal ganglia organization by reinterpreting the functional interaction between the external segment of the pallidum and the subthalamic nucleus in both the normal and pathological state. Indeed, recent neurobiochemical studies have rather unexpectedly shown that the GABAergic and metabolic activities of the external pallidum are not decreased in human and non-human primates with Parkinsonism. This absence of any decrease in activity might be explained by the functionally antagonistic influences of the striatal and subthalamic afferences within the external pallidum, as suggested by several anatomical studies. In addition, there are clues from electrophysiological studies to suggest that the hyperactivity found in the subthalamic neurons in Parkinsonism may not depend solely on the level of activity in the external pallidum. In such a framework, the hyperactivity of the subthalamic neurons would have to be explained, at least in part, by other sources of excitation or disinhibition. However, any explanation for the origin of the subthalamic overactivity in Parkinsonism remains speculative.
Levy
R
R
INSERM U. 289, Hôpital de la Salpêtrière, Paris, France.
Hazrati
L N
LN
Herrero
M T
MT
Vila
M
M
Hassani
O K
OK
Mouroux
M
M
Ruberg
M
M
Asensi
H
H
Agid
Y
Y
Féger
J
J
Obeso
J A
JA
Parent
A
A
Hirsch
E C
EC
D000818:Animals; D001479:Basal Ganglia / Q000033:anatomy & histology* / Q000166:cytology / Q000473:pathology* / Q000503:physiopathology; D005917:Globus Pallidus / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology