Kris M. Horn

Activation of climbing fibers.

Cells in the inferior olive are the sole source of climbing fibers to the cerebellum. In this article, we review some of the discharge properties of olivary cells that are important for understanding its functional role in cerebellar processing. It is generally believed that climbing fiber input supplies the cerebellum with information related to movement errors in order to improve motor performance. As a whole, olivary properties are not consistent with this function. The properties are consistent with the hypothesis that the olive is important for associating arbitrary sensory stimuli with somatosensory events. Although such associations would not be useful for improving the accuracy of motor commands, they may be useful for organizing appropriate behaviors to cope with the predicted event.

Functional Relations of Cerebellar Modules of the Cat

The cerebellum consists of parasagittal zones that define fundamental modules of neural processing. Each zone receives input from a distinct subdivision of the inferior olive (IO)—activity in one olivary subdivision will affect activity in one cerebellar module. To define functions of the cerebellar modules, we inactivated specific olivary subdivisions in six male cats with a glutamate receptor blocker. Olivary inactivation eliminates Purkinje cell complex spikes, which results in a high rate of Purkinje cell simple spike discharge. The increased simple spike discharge inhibits output from connected regions of the cerebellar nuclei. After inactivation, behavior was evaluated during a reach-to-grasp task and during locomotion. Inactivation of each subdivision produced unique behavioral deficits. Performance of the reach-to-grasp task was affected by inactivation of the rostral dorsal accessory olive (rDAO) and the rostral medial accessory olive (rMAO) and, possibly, the principal olive. rDAO inactivation produced paw drag during locomotion and a deficit in grasping the handle during the reach-to-grasp task. rMAO inactivation caused the cats to reach under the handle and produced severe limb drag during locomotion. Inactivation of the dorsal medial cell column, cell group β, or caudal medial accessory olive produced little deficit in the reach-to-grasp task, but each produced a different deficit during locomotion. In all cases, the cats appeared to have intact sensation, good spatial awareness, and no change of affect. Normal cerebellar function requires low rates of IO discharge, and each cerebellar module has a specific and unique function in sensory–motor integration.

Pathways for control of face and neck musculature by the basal ganglia and cerebellum

The basal ganglia are believed to influence movement via thalamo-cortical projections. However, the basal ganglia may also affect brainstem areas involved in movement control such as the red nucleus. The red nucleus receives input from the cerebellum and projects to motor neurons and premotor neurons in the contralateral brainstem and spinal cord. Are there pathways that allow output from the basal ganglia to influence processing in the red nucleus? This study uses the bidirectional tracer, WGA-HRP, to demonstrate that regions of the cat red nucleus receive input from the basal ganglia as well as from the cerebellum. Output from the entopeduncular nucleus, the feline equivalent of the internal segment of the globus pallidus, provides a modest direct input to the red nucleus as well as a more substantial indirect input via projections to the zona incerta and the fields of Forel. Regions of the red nucleus with input from the basal ganglia also receive input from the cerebellar dentate nucleus and lateral regions of interpositus. The regions of the red nucleus receiving basal gangliar input project to the contralateral facial nucleus and upper segments of the cervical spinal cord. Therefore, the red nucleus provides a junction where output from the basal ganglia can interact with output of the cerebellum for movement control of the head and face. The pathway may provide a substrate for a variety of movement disorders that are seen with diseases of the basal ganglia such as cervical dystonia and Parkinsons facies.

Activated autologous macrophage implantation in a large-animal model of spinal cord injury.

OBJECT Axonal regeneration may be hindered following spinal cord injury (SCI) by a limited immune response and insufficient macrophage recruitment. This limitation has been partially surmounted in small-mammal models of SCI by implanting activated autologous macrophages (AAMs). The authors sought to replicate these results in a canine model of partial SCI. METHODS Six dogs underwent left T-13 spinal cord hemisection. The AAMs were implanted at both ends of the lesion in 4 dogs, and 2 other dogs received sham implantations of cell media. Cortical motor evoked potentials (MEPs) were used to assess electrophysiological recovery. Functional motor recovery was assessed with a modified Tarlov Scale. After 9 months, animals were injected with wheat germ agglutinin-horseradish peroxidase at L-2 and killed for histological assessment. RESULTS Three of the 4 dogs that received AAM implants and 1 of the 2 negative control dogs showed clear recovery of MEP response. Behavioral assessment showed no difference in motor function between the AAM-treated and control groups. Histological investigation with an axonal retrograde tracer showed neither local fiber crossing nor significant uptake in the contralateral red nucleus in both implanted and negative control groups. CONCLUSIONS In a large-animal model of partial SCI treated with implanted AAMs, the authors saw no morphological or histological evidence of axonal regeneration. Although they observed partial electrophysiological and functional motor recovery in all dogs, this recovery was not enhanced in animals treated with implanted AAMs. Furthermore, there was no morphological or histological evidence of axonal regeneration in animals with implants that accounted for the observed recovery. The explanation for this finding is probably multifactorial, but the authors believe that the AAM implantation does not produce axonal regeneration, and therefore is a technology that requires further investigation before it can be clinically relied on to ameliorate SCI.

Kainic acid-induced terminal degeneration in the dorsal lateral geniculate of tree shrew

The dorsal lateral geniculate nucleus of tree shrews is very susceptible to the neurotoxic effects of kainic acid. In addition to neuronal loss, there is a profound loss of retinal terminals that is manifested through a disruption of anterograde transport of WGA/HRP from the retina to the kainic acid-lesioned area of the geniculate nucleus. The actions of kainic acid upon both the presynaptic terminals and geniculate neurons may be mediated by a glutamatergic pathway and questions the hypothesis that kainic acid is solely neuron-specific in its toxic action.

Origin of butyrylcholinesterase in the lateral geniculate nucleus of tree shrew

We examined the distribution and possible origins of pseudocholinesterase activity within the lateral geniculate nucleus (LGN) of the tree shrew. Butyrylcholinesterase (BuChE) activity was spread diffusely throughout the LGN and not localized to neuronal perikaryon. Lesions of the LGN eliminated this BuChE activity while not affecting acetylcholinesterase (AChE) activity; however, removal of retinal input by unilateral ocular enucleations failed to affect the BuChE activity within the denervated layers of the LGN. This lack of effect suggests that, unlike the macaque monkey, retinal terminals within the LGN of tree shrew are not the source of BuChE. Thus, in the tree shrew LGN it appears that BuChE is not metabolically related to or dependent upon AChE nor does it originate from retinal sources, but rather BuChE appears to represent an enzyme that is endogenous to the LGN.