John E. Hoover

The Organization of Cerebellar and Basal Ganglia Outputs to Primary Motor Cortex as Revealed by Retrograde Transneuronal Transport of Herpes Simplex Virus Type 1

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.

Input to the primate frontal eye field from the substantia nigra, superior colliculus, and dentate nucleus demonstrated by transneuronal transport.

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.

Sensorimotor corticocortical projections from rat barrel cortex have an anisotropic organization that facilitates integration of inputs from whiskers in the same row

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. J. Comp. Neurol. 466:525–544, 2003.

Overlapping corticostriatal projections from the rodent vibrissal representations in primary and secondary somatosensory cortex.

To determine whether the neostriatum receives overlapping projections from two somatosensory cortical areas, the anterograde tracers biotinylated dextran amine (BDA) and fluoro‐ruby (FR) were injected into the whisker representations of primary (SI) and secondary (SII) somatosensory cortex. Reconstructions of labeled terminals and their beaded varicosities in the neostriatum and thalamus were analyzed quantitatively to compare the extent of overlapping projections to both subcortical structures. Corticostriatal projections from focal sites in both somatosensory areas exhibited substantial amounts of divergence within the dorsolateral neostriatum. Most of the labeled terminals were concentrated in densely packed arborizations that occupied lamellar‐shaped regions along the dorsolateral edge of the neostriatum. Tracer injections in both cortical areas also produced dense anterograde and retrograde labeling in the thalamus, especially in the ventrobasal complex (VB) and in the medial part of the posterior (POm) nucleus. Because these thalamic regions are topographically organized and have reciprocal connections with corresponding representations in both SI and SII, the amount of labeled overlap in the thalamus was used to indicate the degree of somatotopic correspondence at the SI and SII injection sites. We found that the proportion of overlapping projections to the neostriatum was moderately correlated with the amount of overlap observed in the thalamus. This result strongly indicates that specific sites in the dorsolateral neostriatum receive convergent projections from corresponding somatotopic representations in SI and SII, but also suggests that some of the corticostriatal divergence may reflect neostriatal integration of somatosensory information from noncorresponding representations in SI and SII. J. Comp. Neurol. 426:51–67, 2000.

Quantitative comparisons of corticothalamic topography within the ventrobasal complex and the posterior nucleus of the rodent thalamus.

To compare the topographic precision of corticothalamic projections to the ventrobasal (VB) complex and the medial part of the posterior (POm) complex, different anterograde tracers were placed in neighboring parts of the primary (SI) and secondary (SII) somatosensory cortical areas. The location of labeled corticothalamic terminals and their beaded varicosities were plotted, and the digital reconstructions were analyzed quantitatively to determine the extent of overlapping projections from the cortical injection sites. Among animals that received all tracer injections in SI cortex, tracer overlap in the thalamus varied according to the proximity of the cortical injection sites. Regardless of which combination of somatic representations were injected in SI, within each animal the amount of tracer overlap in POm was similar to that observed in VB, and a matched-sample statistical analysis failed to reveal significant differences in the proportion of the labeled regions that contained overlapping projections from the injected cortical sites. Among those animals in which the tracers were injected into the whisker representations of SI and SII, the amount of tracer overlap in the thalamus was not affected by the proximity of the cortical injection sites. Instead, tracer overlap appeared to be related to the degree of somatotopic correspondence. Furthermore, within each of these animals, the amount of tracer overlap in POm was similar to that found in the VB complex. These results indicate that POm has a well-defined topographic organization that is comparable to the degree of topography observed in the VB complex.

The organization of acromiodeltoid and spinodeltoid motor nuclei in rat spinal cord

The retrograde intraaxonal transport of fluorescent dyes (10% Bisbenzimide or 2% Nuclear Yellow) was used to identify the motoneuron populations that control two prime movers of the rat shoulder joint, the acromiodeltoid (Ad) and spinodeltoid (Sd) muscles. The Ad and Sd motor nuclei were both comprised of an average 30-40 motoneurons distributed between spinal segments C5 and C7, in lateral regions of Rexeds lamina IX. Although there was considerable overlap among them, the center of the Ad motor nucleus was consistently located more rostral and medial than that for the Sd motor nucleus.

Retention of a backward classically conditioned reflex response in spinal cat

SummaryRetention of a backward classically conitioned reflex response was investigated in the spinal cat preparation. Facilitation of the flexion reflex was induced by the pairing of superficial peroneal nerve stimulation (30 Hz, 0.5 s), the US (unconditioned stimulus), with saphenous nerve stimulation (10 Hz, 1.5 s), the CS (conditioned stimulus). Both the US and CS were supramaximal for activation of Aδ cutaneous afferent fibers. Experimental animals received 30 paired trials (US preceded CS by 0.25 s) with an intertrial interval (ITI) of three min. Control animals received the same stimuli but in an explicitly unpaired manner. Following acquisition, all animals received 30 additional CS-alone trials at five min intervals. This paradigm, which incorporated ITIs longer than those which had been used previously in backward conditioning studies, induced a long-lasting potentiation of the flexion reflex which appeared to be specific to spinal reflex pathways activated by Aα cutaneous fibers. The relevancy of these results to a more specific understanding of backward and forward classical conditioning in the spinal cat is discussed.