Participation of nucleus entopeduncularis in motor instrumental reflex and entopeduncular influences on motor thalamic nuclei in normal and MPTP-treated cats

Abstract

Activity of entopeduncular neurons was studied in chronic experiments on cats during performance of instrumental movement: pedal pressing and holding. One-hundred and twenty-four neurons were extracellularly investigated in intact animals and 81 neurons in cats treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (5 mg/kg daily, intramuscularly for five days). The mean discharge frequency of nucleus entopeduncularis neurons recorded 48–72 h after the last MPTP injection increased from12.9 ± 1.5 to22.1 ± 1.4impulses/s, but dropped to preinjection values within the next ten days. In intact animals and in MPTP-treated cats 23 and 17%, respectively, of neurons changed their activity before or during the movement performance. Along with nucleus entopeduncularis neurons that changed their activity simultaneously with instrumental movement performance, 16% of nucleus entopeduncularis nerve cells in intact cats and 12% in MPTP-treated cats responded 50–800 ms before the myogramme of working forepaw biceps was started. Excitatory responses associated with movement performance in MPTP-exposed cats were more pronounced, indicating enhancement of nucleus entopeduncularis neuronal activity in animals with injured nigrostriatal system. Since nucleus entopeduncularis neurons are inhibitory cells, the increase in their activity had to be accompanied by reinforcement of inhibitory influence on neurons in motor thalamic nuclei. In order to test this hypothesis, two groups of acute experiments were performed on ketamine-anaesthetized and myorelaxine-immobilized cats. Neuronal responses in ventral anterior and ventral lateral thalamic nuclei to nucleus entopeduncularis stimulation were investigated in normal and MPTP-treated animals in doses that were identical to those administered in chronic experiments. In intact cats, 28% of neurons responded to nucleus entopeduncularis stimulation with the latency shorter than 7 ms. In half of the inhibited neurons after the first phase of inhibition lasting18 ± 2ms, the second inhibitory phase was recorded. The duration of the latter was24 ± 4ms. Although in MPTP-treated cats the number of neurons inhibited by nucleus entopeduncularis stimulation was practically the same as in normal ones (24.5%), the first phase tended to be shorter, and a statistically significant increase of the second inhibitory phase duration (up to50 ± 11ms) was found. It was suggested that changes in the inhibitory processes in motor thalamic neurons receiving afferents from nucleus entopeduncularis could be explained by GABA B-mediated hyperpolarization of the neuronal membrane, evoked by increasing pallidothalamic inhibitory influences.