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Despite extensive behavioural work on the rat superior colliculus, its descending efferent pathways have not been fully characterised with modern anatomical tract-tracing techniques. To investigate these pathways, wheatgerm-agglutinin conjugated with horseradish peroxidase (1%) was injected at various locations within the superior colliculus of hooded rats. Label judged to be transported orthogradely was plotted on coronal sections modified from the atlas of Paxinos and Watson (1982). Two major descending pathways were identified. (i) The bulk of the fibres in the ipsilateral descending pathway leave the superior colliculus ventrolaterally, and course around the lateral margin of the midbrain reticular formation. Caudally, projecting fibres leave the main bundle to innervate the cuneiform nucleus, and parts of the pontomedullary reticular formation. Terminal fields associated with the major bundle of fibres are found in an area medial to the brachium of the inferior colliculus; the parabigeminal nucleus and adjacent tegmentum; the ventrolateral midbrain reticular formation; and the lateral pontine nuclei. (ii) The fibres of the main contralateral descending pathway leave the superior colliculus ventromedially, to cross midline in the dorsal tegmental decussation. They immediately turn caudally to join the predorsal bundle, in which they run the length of the brainstem to reach the cervical spinal cord. Major terminal fields occur in nucleus reticularis tegmenti pontis; the pedunculopontine/parabrachial area; paramedian pontomedullary reticular formation; and inferior olive. In addition there is lighter labelling in many areas of the pontomedullary reticular formation and in the cervical spinal cord. There was also a much sparser contralateral descending projection that crossed midline in the tectal commissure, and sent terminals to the contralateral cuneiform area and adjoining regions. These results suggest that the distribution of the descending efferent pathways from the superior colliculus in rats is similar to those described in other species. The fact that the two major pathways project to quite different terminal areas, together with previous findings that they have separate cells of origin within the tectum, suggests that they may also be functionally distinct.

Recent experimental data has made possible the description of the pathophysiological circuitry that mediates parkinsonism. This work has shown that dopamine-denervated striatal cells discharge abnormally and that this ultimately causes cells in the medial segment of the globus pallidus to become abnormally overactive. The main driving force behind the overactive cells in the medial pallidal segment appears to be excess activity in the afferent pathway to it from the subthalamic nucleus. This pathway is known to use an excitatory amino acid (EAA) as its transmitter. It was therefore hypothesized that local blockade of EAA transmission in the medial segment of the globus pallidus should reverse parkinsonism. This hypothesis was tested in rat and primate models of parkinsonism by the direct injection of the EAA antagonist, kynurenic acid, into the medial segment of the globus pallidus. The results demonstrate that this procedure can reverse parkinsonism in a dose-dependent manner, and suggest that manipulation of EAA transmission in the medial segment of the globus pallidus may have therapeutic potential for treating parkinsonism.

Experiments are described in which the gamma-aminobutyric acid (GABA) antagonist bicuculline was injected into the lentiform complex of conscious monkeys. Injections into either the lateral segment of the globus pallidus, or the medial part of the putamen, gave rise to chorea of the contralateral limbs and/or orofacial region. Control injections of vehicle alone were without effect. Injections of bicuculline into the lateral part of the putamen gave rise to contralateral myoclonus. The chorea produced by lateral pallidal or medial putaminal injections was virtually indistinguishable from the dyskinesia (chorea/ballism) which has been shown, in previous studies, to be induced by injection of GABA antagonists into the subthalamic nucleus. It is proposed that the primary site of action of the GABA antagonist in producing chorea, in the present studies, was the lateral segment of the globus pallidus. The mode of action is suggested to be interruption of GABAergic transmission from the striatum to the lateral pallidal segment. Since this also occurs in Huntington's disease, it is proposed that experimental chorea induced by this method in the monkey may be a useful model of the dyskinesia seen in Huntington's disease in man. Loss of influence of inhibitory striatopallidal fibres would lead to abnormally increased activity of lateral pallidal neurons. These in turn project to the subthalamic nucleus, upon which they have an inhibitory action. Dyskinesia is thus produced by physiological inhibition of the subthalamic nucleus, whose destruction, both in man and the monkey, is known to produce ballism. It is proposed that ballism and chorea share common neural mechanisms, both involving the loss of influence of the subthalamic nucleus on the medial segment of the globus pallidus.