The neural circuits that link the basal ganglia with the cerebral cortex are critically involved in the generation and control of voluntary movement. Retrograde transneuronal transport of herpes simplex virus type 1 was used to examine the organization of connections in the cebus monkey between an output nucleus of the basal ganglia, the internal segment of the globus pallidus (GPi), and three cortical areas: the primary motor cortex, the supplementary motor ara, and the ventral premotor area. Spatially separate regions of the GPi were labeled after virus injections into each cortical area. The GPi projects to multiple cortical motor areas, and this pallidal output is organized into discrete channels. This information provides a new anatomical framework for examining the function of the basal ganglia in skeletomotor control.

We used retrograde transneuronal transport of herpes simplex virus type 1 to map the origin of cerebellar and basal ganglia "projections" to leg, arm, and face areas of the primary motor cortex (M1). Four to five days after virus injections into M1, we observed many densely labeled neurons in localized regions of the output nuclei of the cerebellum and basal ganglia. The largest numbers of these neurons were found in portions of the dentate nucleus and the internal segment of the globus pallidus (GPi). Smaller numbers of labeled neurons were found in portions of the interpositus nucleus and the substantia nigra pars reticulata. The distribution of neuronal labeling varied with the cortical injection site. For example, within the dentate, neurons labeled from leg M1 were located rostrally, those from face M1 caudally, and those from arm M1 at intermediate levels. In each instance, labeled neurons were confined to approximately the dorsal third of the nucleus. Within GPi, neurons labeled from leg M1 were located in dorsal and medial regions, those from face M1 in ventral and lateral regions, and those from arm M1 in intermediate regions. These results demonstrate that M1 is the target of somatotopically organized outputs from both the cerebellum and basal ganglia. Surprisingly, the projections to M1 originate from only 30% of the volume of the dentate and<15% of GPi. Thus, the majority of the outputs from the cerebellum and basal ganglia are directed to cortical areas other than M1.

The purpose of these experiments was to study the subcortical input to the frontal eye field (FEF) and to determine which subcortical structures might project to the FEF via pathways that contain only a single intervening synapse. We used retrograde transneuronal transport of herpes simplex virus type 1 (HSV-1) to label second-order neurons that send information to the FEF of cebus monkeys. The saccade region of the FEF was identified physiologically using intracortical stimulation and then injected with a strain of HSV-1 known to be transported transneuronally in the retrograde direction. Retrograde transport of virus labeled neurons was observed in all the thalamic sites known to innervate the FEF. In addition, we found neurons labeled by transneuronal transport in three subcortical sites: the pars reticulata of the substantia nigra, the optic and intermediate gray layers of the superior colliculus, and a posterior portion of the dentate nucleus of the cerebellum. Each of these sites has been shown in prior studies to project to thalamic regions that innervate the FEF. Moreover, the neurons labeled through transneuronal transport were located in a subregion of each subcortical site that is known to be involved in oculomotor control. These observations demonstrate that signals from the substantia nigra, superior colliculus and dentate nucleus can have a significant influence on the output of the FEF.

We used a dual anterograde-tracing paradigm to characterize the organization of corticocortical projections from primary somatosensory (SI) barrel cortex. In one group of rats, biotinylated dextran amine (BDA) and Fluoro-Ruby (FR) were injected into separate barrel columns that occupied the same row of barrel cortex; in the other group, the tracers were deposited into barrel columns residing in different rows. The labeled corticocortical terminals in the primary motor (MI) and secondary somatosensory (SII) cortices were plotted, and digital reconstructions of these plots were quantitatively analyzed. In all cases, labeled projections from focal tracer deposits in SI barrel cortex terminated in elongated, row-like strips of cortex that corresponded to the whisker representations of the MI or SII cortical areas. When both tracers were injected into separate parts of the same SI barrel row, FR- and BDA-labeled terminals tended to merge into a single strip of labeled MI or SII cortex. By comparison, when the tracers were placed in different SI barrel rows, both MI and SII contained at least two row-like FR- and BDA-labeled strips that formed mirror image representations of the SI injection sites. Quantitative analysis of these labeling patterns revealed three major findings. First, labeled overlap in SII was significantly greater for projections from the same barrel row than for projections from different barrel rows. Second, in the infragranular layers of MI but not in the supragranular layers, labeled overlap was significantly higher for projections from the same SI barrel row. Finally, in all layers of SII and in the infragranular layers of MI, the amount of labeled overlap was proportional to the proximity of the tracer injection sites. These results indicate that SI projections to MI and SII have an anisotropic organization that facilitates the integration of sensory information received from neighboring barrels that represent whiskers in the same row.

We characterized the organization of corticostriatal projections from rodent primary somatosensory cortex (SI), testing the hypothesis that projections from SI areas representing subcomponents of the forelimb exhibit greater neostriatal overlap than projections from areas representing separate body parts. The anterograde tracers Fluoro-Ruby (FR), Alexa Fluor (AF), and biotinylated dextran amine (BDA) were injected into physiologically identified regions of rat SI. Injection locations were confirmed by examining the SI barrel fields and limb representations in tangential sections processed for cytochrome oxidase (CO). Experimental animals were divided into two groups: one group received multiple tracer injections in neighboring SI regions that represent separate body parts (whiskers, forepaw, and hindpaw); the other group received injections in SI areas that represent different components of the forelimb (forepaw, antebrachium, and brachium). The distribution of labeled terminals and their varicosities in the neostriatum and in the thalamus were plotted and quantitatively analyzed. For most animals, tracer overlap in the thalamus was either minimal or completely absent. In the neostriatum, projections from the whisker, forelimb, and hindlimb representations terminated in regions that rarely overlap with each other, while those originating from different parts of the forelimb representation were more likely to terminate in overlapping parts of the neostriatum. To the extent that neostriatal activation depends on corticostriatal convergence, the corticostriatal projections in the sensorimotor channel appeared to be organized so that neostriatal neurons may signal when multiple components of the same body part are activated simultaneously.