The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, cognitive and mnemonic functions. One of their major roles is to integrate sensorimotor, associative and limbic information in the production of context-dependent behaviours. These roles are exemplified by the clinical manifestations of neurological disorders of the basal ganglia. Recent advances in many fields, including pharmacology, anatomy, physiology and pathophysiology have provided converging data that have led to unifying hypotheses concerning the functional organisation of the basal ganglia in health and disease. The major input to the basal ganglia is derived from the cerebral cortex. Virtually the whole of the cortical mantle projects in a topographic manner onto the striatum, this cortical information is 'processed' within the striatum and passed via the so-called direct and indirect pathways to the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata. The basal ganglia influence behaviour by the projections of these output nuclei to the thalamus and thence back to the cortex, or to subcortical 'premotor' regions. Recent studies have demonstrated that the organisation of these pathways is more complex than previously suggested. Thus the cortical input to the basal ganglia, in addition to innervating the spiny projection neurons, also innervates GABA interneurons, which in turn provide a feed-forward inhibition of the spiny output neurons. Individual neurons of the globus pallidus innervate basal ganglia output nuclei as well as the subthalamic nucleus and substantia nigra pars compacta. About one quarter of them also innervate the striatum and are in a position to control the output of the striatum powerfully as they preferentially contact GABA interneurons. Neurons of the pallidal complex also provide an anatomical substrate, within the basal ganglia, for the synaptic integration of functionally diverse information derived from the cortex. It is concluded that the essential concept of the direct and indirect pathways of information flow through the basal ganglia remains intact but that the role of the indirect pathway is more complex than previously suggested and that neurons of the globus pallidus are in a position to control the activity of virtually the whole of the basal ganglia.Key words : Striatum ; globus pallidus ; corticostriatal ; pallidostriatal ; GABA interneurons ; substantia nigra ; synaptic convergence. The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, associative, cognitive and mnemonic functions. The dorsal division of the basal ganglia consists of the striatum (or caudate-putamen), the globus pallidus (GP, external segment of the globus pallidus in primates), entopeduncular nucleus (EP, internal segment of globus pallidus in primates, GPi), the subthalamic nucleus (STN) and the substantia nigra Correspondence to Dr J. P. Bolam,

Cortical afferents to the basal ganglia, and in particular the corticostriatal projections, are critical in the expression of basal ganglia function in health and disease. The corticostriatal projections are topographically organized but also partially overlap and interdigitate. To determine whether projections from distinct cortical areas converge at the level of single interneurons in the striatum, double anterograde labeling from the primary motor (M1) and primary somatosensory (S1) cortices in the rat, was combined with immunolabeling for parvalbumin (PV), to identify one population of striatal GABAergic interneurons. Cortical afferents from M1 and S1 gave rise to distinct, but partially overlapping, arbors of varicose axons in the striatum. PV-positive neurons were often apposed by cortical terminals and, in many instances, apposed by terminals from both cortical areas. Frequently, individual cortical axons formed multiple varicosities apposed to the same PV-positive neuron. Electron microscopy confirmed that the cortical terminals formed asymmetric synapses with the dendrites and perikarya of PV-positive neurons as well as unlabelled dendritic spines. Correlated light and electron microscopy revealed that individual PV-positive neurons received synaptic input from axon terminals derived from both motor and somatosensory cortices. These results demonstrate that, within areas of overlap of functionally distinct projections, there is synaptic convergence at the single cell level. Sensorimotor integration in the basal ganglia is thus likely to be mediated, at least in part, by striatal GABAergic interneurons. Furthermore, our findings suggest that the pattern of innervation of GABAergic interneurons by cortical afferents is different from the cortical innervation of spiny projection neurons.

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Tyrosine Hydroxylase is the rate-limiting enzyme in the synthesis of dopamine, and as such, it is widely used as a marker of dopaminergic cells. Within the basal ganglia, the dopaminergic cells are located in the substantia nigra pars compacta, and project to the striatum. It is this pathway which degenerates during Parkinson's disease. The data presented here illustrate examples of tyrosine-hydroxylase immunoreactive cells in striatum following intrastriatal injection with the neurotoxin MPP+. We further show by electron microscopy that these cells are, in fact, neurons and that they possess ultrastructural features of interneurons.

A method of quantitatively determining the volume of fat emboli in a tissue using an image analysis system (I.B.A.S.) was developed. This procedure is an interactive, semi-automated tool allowing the quick and accurate gathering of large quantities of data from sections of different tissue samples stained by osmium tetroxide. The development of this procedure was aimed at producing a system which is reliable, reproducible and semi-automated thereby enabling epidemiological and serial studies to be made of a large number of histological sections from different tissues. The system was tested in a study of tissue sections from a series of fatalities from an aircraft crash in an attempt at correlating the incidence of fat emboli with the presence of multiple fractures and soft tissue injuries, the correlation to be made being between the quantitative presence of fat emboli and the extent and severity of injuries suffered.