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Integration in descending motor pathways controlling the forelimb in the cat. 11. Inhibitory pathways from higher motor centres and forelimb afferents to C3-C4 propriospinal neurones.

Intracellular recording was made in the C3-C4 segments from cell bodies of a previously described system of propriospinal neurones (PNs), which receive convergent monosynaptic excitation from different higher motor centres and mediate disynaptic excitation and inhibition from them to forelimb motoneurones. Inhibitory effects in these PNs have now been investigated with electrical stimulation of higher motor centres and forelimb nerves. Short-latency IPSPs were evoked by volleys in the cortico-, rubro- and tectospinal tracts and from the reticular formation. Latency measurements showed that those IPSPs which required temporal summation were disynaptically mediated. After transection of the corticospinal tract in C2, only small and infrequent disynaptic IPSPs were evoked from the pyramid. It is postulated that disynaptic pyramidal IPSPs only to a small extent are evoked by monosynaptic excitation of reticulospinal inhibitory neurones known to project directly to the PNs, and that they are mainly mediated by inhibitory interneurones in the C3-C4 segments. Tests with spatial facilitation revealed monosynaptic excitatory convergence from tecto-, rubro- and probably also from reticulospinal fibres on inhibitory interneurones monosynaptically excited from corticospinal fibres (interneuronal system I). Disynaptic IPSPs were also evoked in the great majority of the PNs by volleys in forelimb muscle and skin nerves. A short train of volleys was usually required to evoke these IPSPs from group I muscle afferents. In the case of cutaneous nerves and mixed nerves single volleys were often effective, and the lack of temporal facilitation of IPSPs produced by a train of volleys showed strong linkage from these nerves. The results obtained after transection of the dorsal column at different levels show that the relay is almost entirely rostral to the forelimb segments. Test with spatial facilitation revealed that interneurones monosynaptically activated from forelimb afferents receive convergent excitation from corticospinal but not or only weakly so from tecto- or rubrospinal fibres. There was also convergence from group I muscle afferents and low threshold cutaneous afferents on common interneurones. It is postulated that the disynaptic IPSPs from forelimb afferents are mediated by inhibitory interneurones (interneuronal system II) other than those receiving convergent descending excitation. Volleys in corticospinal fibres, in addition to the disynaptic IPSPs, evoke late IPSPs in the PNs. Similar late IPSPs were evoked from the ipsilateral forelimb by stimulation of the FRA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Glycogen synthesis via the indirect gluconeogenic pathway in the periportal and via the direct glucose utilizing pathway in the perivenous zone of perfused rat liver.

The isolated liver from 24 h fasted rats was perfused in a non-recirculating manner in the ortho- and retrograde direction with erythrocyte-containing (20% v/v) media to provide adequate oxygenation of the liver. Glucose and/or gluconeogenic precursors were added as substrates. Glycogen formation was determined biochemically and demonstrated histochemically. With glucose as the sole exogenous substrate glycogen was deposited in the perivenous area, with gluconeogenic precursors it was formed in the periportal zone during ortho- and retrograde flow. When glucose and gluconeogenic compounds were offered together, glycogen was deposited in both zones. The results corroborate the model of metabolic zonation predicting that periportal glycogen is synthesized indirectly from gluconeogenic precursors while perivenous glycogen is formed directly from glucose.

Animals↗

Anatomy of the giant fibre pathway in Drosophila. I. Three thoracic components of the pathway.

Activity in the flight muscles and jump muscles in Drosophila can be stimulated by excitation of a pair of giant fibres that enter the thoracic ganglion from the brain. Contrary to previous descriptions, these giant fibres are not themselves motor axons. Each giant fibre contacts both a large motor axon and an interneuron. The motor axon innervates the ipsilateral tergotrochanteral (jump) muscle. The interneuron synapses in turn with the motor neurons that innervate the contralateral dorsal longitudinal flight muscle. The output synapses of this interneuron occur directly onto the motor axons within a peripheral nerve. The unusual peripheral location for these interneuron synapses suggests that the interneuron may function to speed up activation of the motor axons by bypassing integration within the motor neurons' dendritic trees. The synapses are typical dipteran chemical synapses, with occasional reciprocal contacts from the motor axons back onto the interneuron. The interneuron-motor axon synapses may be especially useful for morphological studies of identified synaptic contacts because their peripheral location makes them extremely easy to locate and identify.

Animals↗

A cytoskeleton-dependent pathway for induction of IL-2 production and a cytoskeleton-independent pathway for IL-2-mediated signal transduction.

We have used the synthetic microtubule inhibitor Tubulozole C in order to study the role of the microtubule system in human lymphocyte activation. Microtubule disruption prior to activation with phytohemagglutinin (PHA) resulted in a drastic reduction of IL-2 production. Similarly, using OKT3 or PHA as stimulators, a substantial decrease in proliferation was observed. Although IL-2 receptor analysis performed on the stimulated and antitubular-treated lymphocytes showed a 2-fold decrease in high-affinity and a 100-fold decrease in low-affinity IL-2 receptor expression, a proliferative response to externally added rIL-2 was noticed. This occurred provided the triggering agent was excluded or added in suboptimal concentrations. These results indicate that intact microtubules are necessary for PHA/OKT3-induced proliferation and IL-2 production, but not for IL-2-induced proliferation.

Antibodies, Monoclonal↗

cFos labeling in rat superior colliculus: activation by normal retinal pathways and pathways from intracranial retinal transplants.

Previous studies in this laboratory have shown that intracranial retinal transplants can establish both anatomical and functional connections with the host brain. Embryonic rat retinae transplanted intracranially into neonatal host brains are capable of evoking appropriate physiological and behavioral responses when illuminated. The present study employs the specific expression of the cFos protein to identify brain regions in which immediate-early gene activation can be recognized in response to flash stimuli delivered to retinal transplants and to normal intact retinae. Stimulation of the intact eye induced significant cFos expression in various visual centers, including the stratum griseum superficiale of the superior colliculus and the pretectal area, but not in the dLGN, suprachiasmatic nucleus, or retina. Animals with functional transplants expressed cFos throughout the depth of the stratum griseum superficiale and stratum opticum of the superior colliculus, thus apparently activating an additional population of superior collicular cells. Like the eye-stimulated animals, animals with functional transplants failed to elicit significant cFos expression in the dLGN or transplanted retina. This study indicates that intracranial retinal transplants are capable of forming functional connections with the host superior colliculus which not only mediate transient changes in electrical activity but also may affect gene expression through the induction of the c-fos gene.

Animals↗

Tissue factor pathway vs. collagen pathway for in vivo platelet activation.

The roles that the various platelet collagen receptors play in initial platelet adhesion and thrombus growth remain controversial. Here we summarize some of the pertinent data and discuss some recent studies of the initiation and propagation of platelet accumulation into thrombi and the initiation and propagation of thrombin generation. Mice lacking platelet surface glycoprotein VI (GPVI) form normal thrombi in the laser injury model but have a diminished thrombotic response to severe FeCl3 injury. We hypothesize that the paths to thrombus formation in these two models are different with interaction of GPVI and collagen predominant early after severe FeCl3-induced injury but platelet activation by thrombin predominant after laser-induced injury. Understanding of the response to insult in thrombosis models deepens our understanding of the process and provides a firm foundation for evaluation of anti-thrombotic therapy in these models.

Animals↗