Effects of nigral application of muscimol on release of [3H]γ-aminobutyrate and on multi-unit activity in various cat thalamic nuclei

The release of [³H]γ-aminobutyrate (GABA) neosynthesized from [³H]glutamine was estimated in one substantia nigra and in the ipsilateral thalamus of halothane-anesthetized cats by perfusing a [³H]glutamine-enriched physiological medium through a push-pull cannula implanted in the two structures under investigation. After two hours of superfusion, muscimol (10^?6 M) was delivered through the nigral push-pull cannula for 50–60 min and local- and distal-evoked changes of [³H]GABA release were analyzed. In some experiments, changes of global neuronal activity induced by muscimol application were recorded in different thalamic nuclei, using a bipolar electrode. In a few of the above experiments, biochemical and electrophysiological determinations were simultaneously performed in the substantia nigra and the thalamus. The nigral application of muscimol (10^?6 M) induced locally an activation of the substantia nigra reticulata cells, as well as an increase in release of [³H]GABA.Distally, in the thalamus, two types of biochemical and electrophysiological responses were observed according to the localization of the tip of the push-pull cannula or the electrode. (1) An increased release of [³H]GABA and a depression of the global multi-unit cellular activity were obtained in the ventralis medialis-ventralis lateralis, the centralis lateralis and the paracentralis nuclei. These effects could reflect an activation of the GABAergic nigrothalamic neurons projecting to these different thalamic nuclei. (2) In contrast, in the medialis dorsalis paralamellar zone adjacent to the intralaminar nuclei of the thalamus, a decrease of [³H]GABA release and an activation of the multi-unit activity were obtained. These latter results may suggest either a polysynaptic response or the non-GABAergic nature of the nigrothalamic neurons afferent to the medialis dorsalis paralamellar zone.     

Projections of the zona incerta in the cat, with stimulation controls.

In eight cats single electrolytic lesions were placed in the zona incerta, and resultant fiber degeneration studies were made. In seven additional cats, stimulating electrodes were chronically implanted bilaterally into the zona incerta, H₂ (lenticular fasciculus), or H (prerubral) fields of Forel. The animals were placed in a two-compartment shuttle box, and a routinely established procedure of subthalamic stimulation was instituted. When the sensory (nociceptive) or motor manifestations and reactions were established, small lesions were made through both poles of the electrodes. The brains were studied by silver techniques for degenerating axons and terminals. Findings in the latter group of animals with physiologic substrates, compared to those in the first group, indicated that the zona incerta contains at least two major physiologic-anatomic components with differential fiber projections. The first component is a medial zona incerta proper or caudalis, paleospinothalamic, nociceptive-conducting system which causes typical escape responses. Its unequivocal projections are to the nucleus of the H₁ field, posterior and dorsal hypothalamus, part of the intralaminar system, ventromedial and ventralis anterior nuclei, nucleus reuniens, reticular nucleus, pulvinar, posterior nucleus, central gray, red nucleus, and the central tegmental tract. The second constitutent concerns pyramidal-extrapyramidal motor type responses that arise with avoidance reactions from other portions of the zona incerta. In these cases there is heavy projection to the caudate, entopenduncular, globus pallidus, and putamen nuclei. In contrast, degeneration from the nociceptive part of the zona incerta or H₂ and H fields to these nuclei is minimal.     

Escape from and avoidance of nociception elicited by intracranial stimulation of the cat subthalamus

An investigation was undertaken to find out whether cats would learn by a non-aversive auditory cue to avoid a pain-producing intracranial stimulation (ICS) of the subthalamic region. The purpose was to determine whether such ICS produces genuine pain or simply generalized evasive actions. Bipolar stimulating electrodes were implanted bilaterally [into the brain, aimed at] in the H2 (lenticular fasciculus)-H (prerubral) fields of Forel or adjacent part of the zona incerta. The animals were trained initially to escape noxious ICS and, subsequently, to avoid that same noxious ICS when presented with an auditory cue which preceded the ICS by 10 s. After training, lesions were produced through the same electrodes; controls were without lesions. After recovery, both groups were taken through the same escape and avoidance sequence. In eight animals the prelesion avoidance patterns were not significantly altered and remained intact throughout the postlesion testing period. The effective electrode placements extended through the subthalamus to the ventral part of the rostral mesencephalic tegmentum. Fiber projections, with or without terminals, were found in the zona incerta, H1 field, lateral, posterior and dorsal hypothalamus, intralaminar, ventral, and midline thalamic nuclei, and rostral mesencephalic central gray. Certain effective stimulating or ablative neurosurgical procedures for relief of pain in humans are largely consistent with these findings.