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Biomedical subjects

C Hammond

Publications and source records attributed to C Hammond.

At least 73 records · Page 4Linked to original sources

Nucleotide sequence of v-fps in the PRCII strain of avian sarcoma virus.

PRCII is an avian retrovirus whose oncogene (v-fps) induces fibrosarcomas in birds. The viral gene v-fps arose by transduction of an undetermined portion of a cellular gene known as c-fps. PRCII is weakly oncogenic when compared with Fujinami sarcoma virus, another transforming virus containing v-fps. As a first step in the elucidation of the molecular basis for the decreased virulence of PRCII, we have determined the entire nucleotide sequence of v-fps in the PRCII genome. The v-fps domain in PRCII encodes a polypeptide with a molecular weight of ca. 60,500 fused to a portion of the polyprotein encoded by the viral structural gene gag. The hybrid gag-fps polyprotein of PRCII would have a molecular weight of ca. 98,100, in accord with results of previous studies of the protein encoded by the PRCII genome. The leftward junctions between fps and gag in Fujinami sarcoma virus and PRCII are located at the same position in fps, but at different positions in gag. A sequence of 1,020 nucleotides, bounded by direct repeats of 6 nucleotides, is present in v-fps of Fujinami sarcoma virus but absent from PRCII. Our data should permit further explorations of the relationship between structure and function in the transforming protein encoded by v-fps.

Amino Acid Sequence↗

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↗

Intracellular labelling of rat subthalamic neurones with horseradish peroxidase: computer analysis of dendrites and characterization of axon arborization.

Neurones of the rat subthalamic nucleus were identified by their response to cortical stimulation and then intracellularly labelled with horseradish peroxidase. After fixation, the brains were cut serially in sagittal plane and processed by the cobalt chloride-diaminobenzidine procedure. The morphology of nine of the twenty stained neurones strictly located inside the subthalamic nucleus is described by means of quantitative parameters following light-microscopic examination and three-dimensional computer reconstruction. They were all identified as Golgi type I neurones. The somata were ovoidal in shape. A mean of four dendritic stems arose from the soma and gave rise to a mean of 27 tips. The dendrites were thin with long and pedunculated spines. The dendritic fields were ellipsoidal in shape (100 x 600 x 300 micrometer) and were parallel to the principal plane of the nucleus. The dimensions of the dendritic fields are very close to those of the nucleus, and some dendrites cross its limits. The axons gave off two branches, one going caudally and the other rostrally. The caudal-going branch of the axon of one neurone, followed into the substantia nigra, divided into several collaterals coursing dorsoventrally. The rostral-going branch was never followed up to its termination. An intranuclear axonal collateral was observed in only one case. The present data are compared with those obtained from the primate subthalamic neurons. In spite of slight differences in the pattern of dendritic branching, the neurones are similar in both species. However, major differences in the internal organization of the dendritic fields are observed. Dendrites mixing with other neuronal populations were never observed in the primate. Moreover, the relative sizes of the dendritic fields and of the nucleus are strikingly different. This gives to the primate subthalamic nucleus specific and more precisely organized afferent connections.

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↗

Branched output neurons of the rat subthalamic nucleus: electrophysiological study of the synaptic effects on identified cells in the two main target nuclei, the entopeduncular nucleus and the substantia nigra.

The synaptic responses of entopeduncular and nigral cells to subthalamic stimulation were studied with extracellular recording techniques in rats with and without chronic lesions. Entopeduncular output cells were identified by antidromic activation from the lateral habenula, ventral anterior thalamic nucleus and tegmenti pedunculopontine nucleus. Nigral cells projecting to superior colliculus were identified by antidromic discharge. Stimulation of the subthalamic nucleus produced a short latency suppression of spontaneous activity (10-60 ms duration) of 89% of the entopeduncular cells tested in chronically lesioned rats. Of these cells, 50% were identified as projecting to lateral habenula. On the other hand, subthalamic nucleus stimulation produced a short latency excitation of 73% of the nigral cells tested (4.16 +/- 0.07 ms). Forty-eight percent of these cells projected to superior colliculus. The subthalamic fibres which terminate in entopeduncular nucleus and substantia nigra, come from the same neuronal population since the majority, if not all, rat subthalamic neurones send branched projections to both these nuclei. Therefore, the two different types of responses recorded in these nuclei are elicited by the activation of a single neuronal population. This dual effect could be easily explained if one of the responses is mediated by local interneurones. If not, the same transmitter induces the two responses. The entopeduncular nucleus and substantia nigra which are the main target nuclei of the subthalamic nucleus, are also the only known outputs of the striatum. The subthalamic efferent cells could thus modulate the activity of the entire striatal descending output. It is noteworthy that this subthalamic control is different in entopeduncular nucleus than in substantia nigra.

Animals↗

Escape rhythms.

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Arrhythmias, Cardiac↗