George W. Dauth

Glutamate or aspartate as a possible neurotransmitter of cerebral corticofugal fibers in the monkey

We measured high affinity glutamate uptake in subcortical projection sites of monkey (Macaca fascicularis) 8 weeks after unilateral ablation of Brodmanns areas 4 and 6. Uptake decreased ipsilateral to the lesion in ventrolateral nucleus of thalamus, caudate nucleus, and pons. Uptake also decreased contralateral to the lesion in cervical and lumbar spinal cord. These results suggest that L-glutamate (or possibly L-aspartate) is a neurotransmitter of corticofugal fibers in primate.

Chronic Cerebellar Stimulation in the Monkey: Preliminary Observations

In a single monkey, the surface of the cerebellum was stimulated electrically for 205 hours with electrodes and parameter values similar to those currently used in humans for treatment of epilepsy. Im pedance of stimulating and nonstimulating control electrodes remained unchanged throughout an observation period of six months. Potentials evoked by cerebellar stimulation could be recorded from the cranium, providing a noninvasive technique of determining the level of current delivered to cerebellum. Examination of the implantation site showed marked meningeal thickening surrounding the stimulating electrodes. Such thickening was not observed surrounding a control set. Light and electron microscopical examination revealed severe loss of Purkinje cells in tissue near the stimulating electrodes. There was also a moderate loss in other parts of cerebellar cortex down to a depth of about 1 mm from the exposed surface. Biochemical analysis revealed metabolic abnormalities consistent with the morphologic evidence of widespread tissue damage.

Development and Evaluation of a New Water-Soluble lodinated Myelographic Contrast Medium with Markedly Reduced Convulsive Effects1

A new water-soluble myelographic contrast agent with more hydrophilic properties than metrizamide was developed and tested in the primate (Macaca mulatto) and the cat. A new animal model that allows study of the convulsive effects of intrathecally administered contrast agents in the awake monkey was designed. With this sensitive model the new contrast agent was shown to have a remarkably reduced convulsive effect when compared with metrizamide and other media. Intrathecal hypertonic solutions in the cat depress the evoked cortico-spinal responses whereas the neurotoxic effects of the iodinated water-soluble contrast media increase them. The net effect is a combination of the two actions.

Alteration of Purkinje cell activity from transfolial stimulation of the cerebellum in the cat

The activity of single Purkinje cells and other single neural units was recorded extracellularly from the cerebellar cortex of anesthetized cats during surface cerebellar stimulation with parameters similar to those used in human beings with epilepsy. At a stimulation rate of 0.5 Hz, most Purkinje cells responded with a simple stimulus-locked suppression of activity, although some showed more complex sequences of suppression and activation. At a stimulus rate of 10 Hz, essentially all responsive Purkinje cells showed a suppression of activity. Most of the other units responded to stimulation in the same manner. These effects were observed immediately adjacent to the stimulating electrodes and as far away as 6.5 mm. Therefore, surface stimulation of the cerebellum with parameters equivalent to those used in epileptic patients suppresses rather than activates Purkinje cells. These findings do not support the hypothesis that Purkinje cell activation accounts for seizure suppression in epileptic patients.

Chronic cerebellar stimulation in the monkey Electron microscopic and biochemical observations

The effects of chronic electrical stimulation to the surface of cerebellum in the Macaca mulatta monkey were studied with morphologic and biochemical techniques. There was considerable damage and loss of Purkinje cells in all specimens examined, including an area without electrodes, but the greatest changes appeared in tissue beneath the cathode and anode. Despite the damage, normal appearing synapses persisted in the molecular layer of all specimens. Fibrous glial processes were more numerous beneath the cathode. There were abnormalities in gamma-amino butyric acid (GABA) and polyamine concentrations in virtually all specimens, consistent with the morphologic evidence of widespread tissue damage.

Spontaneous neuronal unit activity in the primate basal ganglia and the effects of precentral cerebral cortical ablations

The discharge properties of single neuronal units in the putamen, caudate nucleus, and globus pallidus were studied in awake primates. The effects of restricted deafferentation of the striatum were determined by recording single unit activity in animals with unilateral ablation of areas 4 and 6 of Brodmann. The most striking change was on the regularity of unit firing in the putamen. Units in the normal putamen exhibited a wide range of firing rates and variability. In many units discharge rate was very slow. After the lesion, putaminal units discharged in steady spike trains with highly regular patterns of interspike intervals having on average a 63% reduction in the coefficient of variation. Contrary to expectations, average firing rates actually increased slightly (22%) from a median value of 4.88 Hz in controls to 5.95 Hz in lesioned animals. Although the rates and variability observed in lesioned animals completely overlapped the range of the sample observed in controls, the distributions were shifted such that there were more units with regular discharge patterns and slightly faster firing rates. The caudate nucleus showed no significant change in firing rate or variability. In the globus pallidus, firing rate decreased significantly in the internal segment, and both segments showed an increase in discharge variability. The findings demonstrate that the cerebral cortex strongly influences the spontaneous discharge properties in the basal ganglia. The effects on the variability of spontaneous activity are greater than on the maintenance of tonic firing.

Effect of Isotonic Contrast Agents on Spinal Reflexes in the Cat

The effects of isotonic solutions of three contrast agents, administered intrathecally, were studied in cats. A pronounced increase in the electrically evoked cortico-spinal responses and segmental spinal polysynaptic reflexes was recorded after administration of methylglucamine diatrizoate. Injection of methylglucamine iothalamate resulted in an increase of the amplitudes of these reflexes, while metrizamide did not show any consistent effect. The data suggest that water-soluble media have direct effects upon spinal gray matter.

Computer-assisted estimates of lesion sizes and shrinkage in denervated areas from receptor autoradiograms using a digitizing tablet

Area measurements taken from receptor autoradiograms were employed to estimate the size of striatal kainate lesions and the amount of shrinkage in deafferented projection areas. There was no significant difference in the size of substantia nigra (SN) on the denervated side as compared to the intact side one week and one month after unilateral striatal lesions. Although there was no change in the size of globus pallidus (GP) on the lesioned side one week after the lesion, there was a 17% shrinkage one month after the lesion. At 3-4 months after the lesion, the amount of shrinkage was 19% in SN and 16% in GP.