Comparisons of nerve fiber growth from three major catecholamine-producing cell systems: adrenal medulla, superior cervical ganglion, and locus coeruleus.
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Biomedical subjects
Publications and source records attributed to L Olson.
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The effect of opiate peptide administration on the electrical activity of intraocular hippocampal transplants was studied. Similar to observations in situ, the administration of beta-endorphin or methionine enkephalin produces a concentration-dependent increase in the firing rate of identified pyramidal neurons within hippocampal formation transplants. In addition, these peptides elicit a profound increase in 'EEG' amplitude, which ultimately develops into epileptiform activity. The ability of naloxone to either reverse or prevent the peptide-induced changes in both single unit and EEG activity supports the hypothesis that the excitatory response of the hippocampus to opioid peptides is mediated via an opiate receptor. The results of this study also suggest that the excitatory response to the opiate peptides in hippocampus is the result of alterations in intrinsic neuronal circuitry and is not dependent upon extra-hippocampal afferents.
In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.
Quinacrine, a fluorescent antimalarial acridine derivative, selectively binds to a population of nerve cell bodies and nerve fibers in Auerbach's plexus and elsewhere in the gut. This quinacrine-binding, as measured by fluorescence intensity, is reduced if the nervous elements are depolarized by high K+ (80--150 MM) or veratridine (5 x 10(-5) M) during quinacrine incubation. A reduction of quinacrine-content in nerve terminals is also seen when depolarization (veratridine) takes place for 2 min after quinacrine-incubation, indicating a release of already bound quinacrine. If terminals are depolarized (high K+ or veratridine) before quinacrine incubation, a reduction of quinacrine content is also seen. The depolarization-induced reduction of quinacrine-binding is blocked by Ca2+-removal and, in the case of veratridine by tetrodotoxin. Our findings suggest that quinacrine binds to a compound that is released by nervous activity. Binding mechanism remains to be elucidated. The possibility that quinacrine visualized purine-rich structures is discussed.
Sequential intraocular grafting of defined areas from fetal rat brain to adult host rats was used to explore the possibility that such double grafts would become interconnected. Norepinephrine- containing neurons of the locus coeruleus were grafted together with either parietal cerebral cortex, hippocampus, or the caudate nucleus. Dopamine-containing neurons of the substantia nigra were transplanted together with either parietal cerebral cortex or the caudate nucleus. The brainstem grafts showed good survival and development in oculo, using both histochemical and electrophysiological criteria. Locus coeruleus neurons were found to innervate cerebral cortex, hippocampus, and the caudate nucleus. Substantia nigra neurons invaded cerebral cortex abundantly, with a terminal distribution typical of cortical DA terminals in situ. The innervation of the caudate nucleus from substantia nigra transplants was variable, but areas of dense confluent terminals were observed. We conclude that sequential brain grafting in oculo permits generation of isolated yet defined catecholaminergic projections, which are suitable for electrophysiological, pharmacological, and histochemical studies.
Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.
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Hemodynamic, pulmonary, and renal variables were measured in 24 patients scheduled for major abdominal aortic operations. Control values were obtained before preoperative medications were given. All patients received 5% dextrose in Lactated Ringer's solution intraoperatively. Postoperatively, group 1 patients received 5% dextrose in water plus albumin, group 2 received 5% dextrose in 0.45 sodium chloride solution, and group 3 received 5% dextrose in lactated Ringer's solution. There were significant increases in Qs/Qt and AaDO2, 48 hours after operation in group 3. Oxygen consumption and cardiac output increased in all groups 24 hours after operation. Twenty-four hours later, these two variables returned to control values in group 1 but continued to rise in the other two groups. Significant diuresis occurred in group 1, 48 hours postoperatively, whereas the other two groups continued to retain water. Use of albumin and 5% dextrose in water in the postoperative period seemed to produce less deviations from control values of most measured variables, than the other two groups.
The present study examines whether the developing noradrenergic neurons of locus coeruleus depend on endogenous nerve growth factor (NGF) for nerve fiber production and if exogenous NGF stimulates fiber growth in this nucleus, using a collagen gel tissue culture technique. Lucus coeruleus from perinatal rat brain was used in three culture experiments: (1) lucus coeruleus, parietal cerebral cortex, and the superior cervical ganglion, prepared from newborn rats and cultured in different sectors of the same dishes; (2) locus coeruleus and parietal cerebral cortex from 17-day-old rat fetuses cultured in the same manner, and (3) locus coeruleus from 17-day-old rat fetuses co-cultured with spinal, sympathetic and ciliary ganglia from 8-day chick embryos. Experiments 1 and 2 were run with and without addition of NGF and anti-NGF, experiment 3 with and without anti-NGF. Total fiber production in all cultured tissues was evaluated daily by dark field and phase contrast microscopy during 4 days. Adrenergic nerve fiber production was then studied in the same locus coeruleus and superior cervical ganglia from the rats by Falck-Hillarp fluorescence histochemistry. Locus coeruleus and cortex cerebri from fetal rats produced dense fiber halos in culture. Locus coeruleus from newborn rats produced considerably less fibers, newborn cortex only few fibers. Superior cervical ganglia from the same newborn animals produced no or almost no fibers. Addition of NGF was not able to stimulate fiber growth in locus coeruleus nor in cortex cerebri as observed both in the living cultures and by fluorescence microscopy. Likewise, addition of anti-NGF did not affect fiber production in the CNS areas. The negative results with NGF on newborn locus coeruleus and cortex cerebri were in sharp contrast to the strong, highly significant fiber growth response demonstrated by the superior cervical ganglion from the same animals cultured in the same dishes. The third experiment tested whether locus coeruleus in tissue culture contained or produced nerve growth factor or any one of the three chick embryo ganglia. No response whatsoever in these three ganglia was observed. It is concluded that the developing locus coeruleus area does not contain or produce NGF, does not depend on NGF for fiber production, and is not stimulated by exogenous NGF.
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The anococcygeus muscle exhibits non-cholinergic, non-adrenergic, inhibitory neurotransmission. In the present paper we describe the presence of quinacrine-binding beaded nerve fibres in the mouse anococcygeus muscle. A large number of fibres were running parallel to the smooth muscle bundles. A second distribution of fibres formed an irregular plexus. No quinacrine-binding nerve cell bodies were found within the muscle. When the anococcygeus muscle was cut close to its insertion in the rectum, the proximal part lost most of its quinacrine-binding nerves 2-7 days after transsection. The results demonstrate a correlation between presumed non-cholinergic non-adrenergic neurotransmission and quinacrine-binding nervous elements.
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Fetal rat hippocampus, cerebellum, and heart were homologously transplanted to the anterior chamber of the eye of adult female recipients. After the grafts were allowed to mature in oculo, ingrowing adrenergic and cholinergic fibers from the iris were activated by changing the illumination of the retina. Electrophysiological recordings from all three types of transplants showed changes similar to those reported for effects of adrenergic and and cholinergic inputs in situ. Pharmacological studies with the transplants indicated that these electrophysiological changes were caused by activation of local muscarinic cholinergic and beta-adrenergic synapses. These data suggest that the intraocular graft is able to induce functional adrenergic and cholinergic inputs from the ground plexus of the iris and support the hypothesis that target organ influences play an important role in synaptogenesis.
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Locus coeruleus from fetal donors was homologously grafted to the anterior eye chambers of adult rats whose eyes were sympathetically denervated. After intraocular maturation, outgrowth of noradrenaline-containing fibres from the locus coeruleus neurons on the host iris was studied by Falck--Hillarp fluorescence histochemistry. In control animals locus coeruleus grafts produce a halo of noradrenaline-containing nerve fibres around the graft, covering approximately one third of the surface of the host iris. Sensory denervation of host eyes carrying maturated locus coeruleus grafts was produced by intracranial lesions of the trigeminal nerve. Such lesions induced a rapid growth response in the grafted locus coeruleus neurons, leading within three weeks to complete innervation of the host iris. It was concluded that removal of non-sympathetic, non-parasympathetic nerve fibres on the host iris elicits a strong fibre-growth response in the grafted locus coeruleus.
Biochemical studies showing that lead (Pb++) inhibits cerebellar adenylate cyclase (IC50 = 2 micrometer) prompted us to test the effects of this cation on the depression of spontaneous discharge of Purkinje (P) cells produced by iontophoresis of norepinephrine (NE). Previous studies have suggested that the effects of NE on P cell discharge may be mediated by activation of a NE-sensitive adenylate cyclase. Iontophoresis of Pb++ in situ, and in cerebellar transplants in oculo, reliably antagonized NE responses in over 80% of the P cells studied in both preparations. Blockade was readily seen at iontophoretic currents of 5 to 10 nA. Superfusion of PB++ (5--10 micrometer) into the anterior eye chamber also antagonized NE responses in P neurons of the transplant. Spontaneous discharge rate was either unaffected or slightly elevated at Pb++ levels that almost completely blocked NE. Barium, a heavy metal which does not inhibit adenylate cyclase in vitro, did not block NE effects. Stimulation of parallel fibers or iontophoresis of acetylcholine excited P cells. No antagonism was seen, however, between Pb++ and these acetylcholine or parallel fiber excitations. These results raise the possibility that blockade of brain catecholamine receptors may partially underlie the central nervous system toxicity seen with lead administration.
Almost all catecholamine (CA)-containing nerve terminals in the ventral column, intermediate grey and ventral half of the dorsal column disappeared after bilateral stereotaxic lesions of nucleus locus coeruleus, as revealed by fluorescence histochemistry. Some of the CA nerve terminals in the dorsal half of the column seemed to be unaffected by the lesions, as well as the CA terminals innervating the thoracic sympathetic lateral column and the band of nerve terminals crossing the midline and innervating the central grey. This coeruleo-spinal pathway in the rat is located in the anterior funiculus and the ventral parts of the lateral funiculus. A schematic map of the different CA projections to the spinal cord is presented. It was concluded that locus coeruleus innervates almost all parts of the central nervous system.
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