Synergistic influences of the striatum and the globus pallidus on posturaland locomotor control

We have investigated the role of the globus pallidus in locomotor and postu ral control in a previously established animal model of striatal dysfunctio n. Striatal efferent activity was suppressed by intracerebral infusions of antisense oligodeoxynucleotides targeted to the messenger RNA of the proto- oncogene, c-fos. This suppression produced robust circling behavior and an atypical expression of c-fas in the ipsilateral globus pallidus following p sychostimulant challenge. Simultaneous infusions of antisense oligodeoxynuc leotides into both the caudate-putamen and the ipsilateral globus pallidus produced an approximate threefold increase in the intensity of rotation eli cited by D-amphetamine. Excitotoxic lesioning of the globus pallidus produc ed marked postural asymmetry and circling behavior upon stimulation. The in tensity of this rotational behavior was similar to that produced by dual in fusions of antisense oligodeoxynucleotides into the caudate-putamen and the globus pallidus, and was not further potentiated by suppression of striata l c-fos expression. These results demonstrate the importance of the globus pallidus in postural and motor control, and suggest that activation of this nucleus through a r eduction in striatopallidal inhibition may function to balance the output a ctivity of the basal ganglia. (C) 1999 IBRO. Published by Elsevier Science Ltd.