Behavioural disorders induced by external globus pallidus dysfunction in primates: I. Behavioural study.
The current model of basal ganglia organization postulates the existence of a functional partitioning into sensorimotor, associative and limbic territories, implicated in motor, cognitive and emotional aspects of behaviour, respectively. This organization was proposed initially on the basis of the cortico-striatal projections and was extended to the various structures of the basal ganglia. While there is a considerable body of experimental evidence in support of an involvement of the basal ganglia sensorimotor territory in basic control of movements, evidence for the functional relevance of the non-motor territories has had to be based on a growing number of clinical observations due to the paucity of relevant animal studies. Previous studies in monkeys have, however, shown that a reversible and focal dysfunction induced by microinjections of bicuculline in the sensorimotor territory of the external globus pallidus (GPe) can generate abnormal movements. We therefore hypothesized that the same approach applied to the associative and limbic territories of the GPe would induce behavioural disorders rather than abnormal movements. To address this hypothesis, we performed microinjections of bicuculline, using the same concentration in each of the sensorimotor, associative and limbic territories of the GPe, as defined by striato-pallidal projections. Spontaneous behaviour and performance of a simple food-retrieving task during the effects of these microinjections were compared with data obtained in control conditions in the same monkeys. We found that bicuculline microinjections induced stereotypy when performed in the limbic part of the GPe, and attention deficit and/or hyperactivity when performed in the associative part. No movement disorders were observed during these behavioural disturbances. As previously described, abnormal movements were observed when bicuculline was injected into the sensorimotor territory of the GPe. The relationship between the localization of microinjection sites and the type of behavioural effect was similar for the three monkeys. Control microinjections of bicuculline into surrounding structures (striatum and internal globus pallidus) and saline injections into the GPe failed to induce any observable effect. These results support the hypotheses of functional diversity and territorial specificity in the GPe, in agreement with the parallel circuits organizational model of the basal ganglia. Furthermore, the behavioural effects shared similar features with symptoms observed in Tourette's syndrome, attention deficit/hyperactivity and compulsive disorders. Thus, our study provides experimental evidence for the involvement of the associative and limbic parts of the basal ganglia in these pathologies. These results may provide the basis for a primate model of these disorders.
Neurologie et Thérapeutique expérimentale, INSERM U289, Hôpital de la Salpêtrière, Paris, France.
David
D
Grabli
Kevin
K
McCairn
Etienne C
EC
Hirsch
Yves
Y
Agid
Jean
J
Féger
Chantal
C
François
Léon
L
Tremblay
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline; D001927:Brain Diseases / Q000139:chemically induced* / Q000503:physiopathology; D002522:Chlorocebus aethiops; D003292:Convulsants; D003342:Corpus Striatum / Q000187:drug effects; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D008845:Microinjections; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology; D009483:Neuropsychological Tests; D013239:Stereotyped Behavior / Q000187:drug effects
D003292:Convulsants; D001640:Bicuculline