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Biomedical subjects

A R Crossman

Publications and source records attributed to A R Crossman.

At least 109 records · Page 6Linked to original sources

Experimental hemichorea/hemiballismus in the monkey. Studies on the intracerebral site of action in a drug-induced dyskinesia.

Antagonists of the neurotransmitter gamma aminobutyric acid (GABA) were injected at seventy intracerebral sites in the conscious monkey. Injections located in or near to the subthalamic nucleus provoked involuntary movements of the contralateral limbs. These movements had the characteristics of chorea and, when severe, resembled hemiballismus as seen following subthalamic nucleus lesions in man and monkey. Localized injections of GABA antagonists into the medial segment of the globus pallidus were without observable effect on motor activity. These observations are discussed with regard to the role of GABA in subthalamopallidal relations. Injection of GABA antagonists at some other sites provoked different forms of dyskinesia. Injections in or near the zona incerta adjacent to the subthalamic nucleus induced torticollis and circling behaviour either in isolation or in addition to contralateral limb dyskinesia. Injections at some sites located in the lateral segment of the globus pallidus or in the putamen induced choreoathetoid or myoclonic movements, respectively.

Animals↗

Microiontophoretic studies on the nature of the neurotransmitter in the subthalamo-entopeduncular pathway of the rat.

The aim of the present study was to determine the identity of the neurotransmitter released by the pathway from the subthalamic nucleus to the entopeduncular nucleus in the rat, using extracellular stimulating and recording techniques and microiontophoresis. In order to avoid stimulation of passing fibers at the level of the subthalamic nucleus, (collaterals to the entopeduncular nucleus of the caudato-nigral pathway, or direct projections to the entopeduncular nucleus from the substantia nigra or nucleus tegmenti pedunculopontinus), the experiments were performed in rats bearing chronic ipsilateral lesions in order to make these pathways degenerate. Under such conditions, subthalamic nucleus stimulation suppressed the spontaneous firing of all the entopeduncular nucleus cells studied (n = 40) for 15-25 ms (mean duration +/- S.E.M.:21.88 +/- 1.57 ms). Entopeduncular nucleus cells were identified by antidromic activation from the ventral anterior thalamic nucleus (40%) or lateral habenula nucleus (68%). Low doses of iontophoretically applied GABA (60 cells) or glycine (15 cells) were inhibitory upon entopeduncular cells, while acetylcholine or carbamylcholine were poorly excitatory (18 cells), or had no effect (28 cells). The subthalamic nucleus-evoked inhibition of entopeduncular neurons was reversed by microiontophoretically applied bicuculline or picrotoxin, at doses which blocked the GABA-induced response, but not that produced by glycine or acetylcholine. With similar experiments, strychnine and atropine were ineffective. This excludes a possible role of glycine or acetylcholine in the subthalamic-evoked inhibitory response of entopeduncular cells. The present study strongly suggest that GABA is a neurotransmitter in the inhibitory subthalamo-entopeduncular pathway.

Acetylcholine↗

A remotely operated pump for intracerebral micro-injection in the primate.

A method is described for making small (2-6 microliters) localized intracerebral drug injections in the conscious monkey. A base plate and guide cannula are initially secured to the skull under general anaesthesia. A mechanical pump containing the drug solution and fitted with an injection needle is located on the base plate assembly. In the conscious animal the pump is triggered magnetically to deliver a predetermined volume into the target brain region.

Animals↗

Anatomical and electrophysiological studies on the reciprocal projections between the subthalamic nucleus and nucleus tegmenti pedunculopontinus in the rat.

Reciprocal projections between the subthalamic nucleus of the diencephalon and the brain stem nucleus tegmenti pedunculopontinus have been demonstrated and studied anatomically and electrophysiologically in the rat. Injections of the fluorescent compound Fast Blue into pedunculopontinus and the surrounding peribrachial region of the mesencephalon gave rise to retrogradely-labelled neurone cell bodies in the ipsilateral subthalamic nucleus. A minimum of 1% of subthalamic nucleus neurones appeared to contribute to this projection. Electrical stimulation of the subthalamic nucleus in chronically decorticated rats resulted in inhibition of extracellularly recorded ipsilateral pedunculopontine cells which had themselves been identified (by antidromic activation) as projecting rostrally as far as the subthalamic nucleus or entopeduncular nucleus. Injection of the enzyme horseradish peroxidase into the subthalamic nucleus resulted in retrograde labelling of neurones in the ipsilateral nucleus tegmenti pedunculopontinus with additional contralateral labelling in some animals. Similar pedunculopontine labelling was not seen after injection of horseradish peroxidase into either the zona incerta or lateral hypothalamus. Stimulation of the subthalamic nucleus gave rise to antidromic activation of some neurones in nucleus tegmenti pedunculopontinus. The rate of conduction of the pedunculopontine-subthalamic projection was estimated to be approximately 1.7 m/s. Electrical stimulation of pedunculopontinus gave rise to orthodromic activation of some subthalamic nucleus neurones which had themselves been identified (by antidromic activation) as projecting to the globus pallidus or substantia nigra. The nucleus tegmenti pedunculopontinus is in a position to fulfill two roles--to control the activity of rostrally-located motor centres such as the globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra and, by reciprocal connections, to mediate in part the effects of these structures on the lower motor system. The observations presently described are a first step in the analysis of the potential role of the pedunculopontine nucleus in the modulation of activity in, and the mediation of activity from, the basal ganglia and related motor structures of the diencephalon and mesencephalon.

Animals↗

Nucleus tegmenti pedunculopontinus: efferent connections with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport of horseradish peroxidase.

The efferent connections of the brain stem nucleus tegmenti pedunculopontinus were studied in the rat using the techniques of anterograde and retrograde transport of the enzyme horseradish peroxidase, laying particular emphasis on that part of pedunculopontinus which receives direct descending projections from the basal ganglia and related nuclei. In a preliminary series of experiments horseradish peroxidase was injected into either the entopeduncular nucleus or the subthalamic nucleus and, following anterograde transport of enzyme, terminal labelling was identified in nucleus tegmenti pedunculopontinus, surrounding the brachium conjunctivum in the caudal mesencephalon. In a subsequent series of experiments, horseradish peroxidase was injected into that region of nucleus tegmenti pedunculopontinus which receives entopeduncular and subthalamic efferents and its efferent projections were studied by anterograde transport of the enzyme. The results indicate that nucleus tegmenti pedunculopontinus gives rise to widely distributed efferent projections which terminate rostrally in mesencephalic, diencephalic and telencephalic structures and caudally in the pontine tegmentum. In the mesencephalon, terminal labelling was found in the pars compacta of the ipsilateral substantia nigra and sometimes in the adjoining ventral tegmental area. Labelling was also found in the ipsilateral half of the periaqueductal grey. In the diencephalon terminal labelling occurred bilaterally in the subthalamic nucleus and ipsilaterally in the intralaminar nuclei of the thalamus. Further rostrally, terminal labelling was particularly evident in the ipsilateral pallidal complex, especially in the caudal two-thirds of the entopeduncular nucleus and the ventral half of the caudal third of the globus pallidus. Caudal to pedunculopontine injection sites dense labelling was observed in the reticular formation of the pontine tegmentum. In a final series of experiments, confirmation of apparent pedunculopontine efferent projections was sought using the retrograde transport of horseradish peroxidase. Enzyme was injected into sites possibly receiving pedunculopontine efferents and the peribrachial area of the brain stem was examined for retrograde cell labelling. In this way, pedunculopontine projections were confirmed to the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra, parafascicular nucleus and pontine reticular formation. Injections into the globus pallidus or subthalamic nucleus gave rise to retrograde cell labelling bilaterally in pedunculopontinus. In addition, retrograde transport studies alone demonstrated projections from pedunculopontinus to the cerebral cortex and to the spinal cord. It is concluded that the nucleus tegmenti pedunculopontinus has reciprocal relationships with parts of the basal ganglia and some functionally related nuclei (in particular, the pallidal complex, subthalamic nucleus and substantia nigra).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Autoradiographic demonstration of binding sites for [3H]desipramine in rat brain.

Many of the characteristics of [3H]desipramine ([3H]DMI) binding sites, previously established with brain homogenates, were confirmed in slide-mounted sections of rat forebrain. A 1:1 ratio of specific to non-specific binding was established. The proportion of specifically bound [3H]DMI was reduced in brain sections from rats pretreated with 6-hydroxydopamine but not with 5,6-dihydroxytryptamine. High resolution localization of [3H]DMI binding sites was achieved by exposing the sections to tritium-sensitive film.

Animals↗

Subthalamic projection to nucleus tegmenti pedunculopontinus in the rat.

A projection from the subthalamic nucleus to the nucleus tegmenti pedunculopontinus has been demonstrated in the rat using retrograde and anterograde transport of horseradish peroxidase. Small, well-localized injections of peroxidase in nucleus pedunculopontinus gave rise to retrogradely labelled cell bodies in the subthalamic nucleus. Injections of peroxidase restricted to the subthalamic nucleus gave terminal labelling in nucleus pedunculopontinus.

Animals↗

An in vivo method for testing putative GABA-like compounds.

A technique is described that enables compounds with GABA-ergic properties to be rapidly identified in vivo. Electrical stimulation of the neostriatum in the conscious rat evoked a contralateral head-turn. Evidence is presented that this easily timed motor response involves, at least in part, GABA-ergic mechanisms in the globus pallidus. GABA drugs were injected through a cannula into the ipsilateral globus pallidus and their effects on head-turning observed. Known GABA agonists including muscimol slowed the head-turn, whereas the GABA antagonist picrotoxin facilitated it. A number of drugs such as baclofen, diazepam, and pentobarbitone which have been attributed with GABA-like properties behaved like GABA agonists in the head-turn model following either intrapallidal or intraperitoneal injection. Other drugs, e.g. tranquillizers, with no known GABA-like properties, did not effect the head-turn time.

Animals↗