Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced injury of dopaminergic nigrostriatal system on movement components of the instrumental reflex and motor thalamic neurons' reactions in the cat.

Peculiarities of excitation and inhibition in ventral lateral and ventral anterior thalamic neurons were studied in cats with movement disorders (bradykinesia and muscle rigidity) induced by injury of nigrostriatal dopaminergic neurons with neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (5 mg/kg daily, intramuscularly for five days). As was shown in chronic experiments, mean discharge frequency of neurons related to initiation of upper limb movements increased. Excitation of these neurons coincided with movement initiation, flexion and extension becoming more prominent and prolonged as compared with normal animals. In parallel to those changes, bradykinesia developed. In acute experiments performed under ketalar anaesthesia and myorelaxine immobilization it was found that neurotoxin caused a decrease of the inhibition duration and effectiveness in relay and non-relay thalamic motor nuclei neurons. The inhibition deficiency was accompanied by a shortening of latencies of orthodromic responses evoked by red nucleus stimulation. Two days after the last neurotoxin injection, light microscope examination revealed that about 48% of neurons located in the pars compacta of substantia nigra were destroyed. Electron microscopic analysis showed hydropic changes in perykaria and dendrites in most neurons of the substantia nigra pars compacta that are typical of the light type of degeneration. Pathomorphological processes in the synaptic apparatus were also found. The content of dopamine in the caudate nucleus fell to 30% as compared with intact animals. The suggestion is made that the deficiency of inhibition developed in motor thalamic neurons in response to nigrostriatal system destruction results from attenuation of dopamine-modulated direct GABAergic nigrothalamic influences and/or might be connected with increased inhibition of inhibitory interneurons of the same thalamic nuclei conditioned by pallidum disinhibition.

Unitary responses of the caudate nucleus to direct stimulation.

Unitary responses of the caudate nucleus to stimulation of various parts of it were investigated by extracellular recording. Latent periods of response discharges varied from 3.5 to 40 msec. Most neurons were excited by stimulation of the most rostral part of the head of the caudate nucleus. Irrespective of the site of stimulation, in most cases responses consisted of initial excitation in the form of one or, less frequently, two discharges followed by a period of depression of spontaneous activity. Recovery of activity took place gradually, without postinhibitory facilitation. No afterdischarges or periodic repetitions of spikes were observed after the initial response. Repetitive stimulation of the caudate nucleus showed that the neurons of this nucleus reproduce frequencies of stimulation badly above 30/sec, and under these circumstances in many cases they continued to discharge on average at a frequency of 5--15/sec. The results are examined from the standpoint of participation of the caudate nucleus in the formation of spindle activity.