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Biomedical subjects

G R Siggins

Publications and source records attributed to G R Siggins.

At least 91 records · Page 5Linked to original sources
PubMed1979

Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurons.

The atypical excitation by opiates and opioid peptides of hippocampal pyramidal cells can be antagonized by iontophoresis of naloxone, the gamma-aminobutyric acid antagonists bicuculline, or magnesium ion. The recurrent inhibition of these cells evoked by transcallosal stimulation of the contralateral hippocampus is blocked by enkephalin but only shortened by acetylcholine. The results suggest that the opioids excite pyramidal neurons indirectly by inhibition of neighboring inhibitory interneurons (probably containing gamma-aminobutyric acid). This mechanism may be pertinent to the electrographic signs of addictive drugs.

Animals↗
PubMed1979

Neurotransmitters and neuromodulators and their mediation by cyclic nucleotides.

An effort has been made here to devise criteria allowing discrimination between neurotransmitters, modulators and mediators. However, after consideration of several technical pitfalls in studies of these criteria, and examination of the properties of two examples of neuroactive agents (norepinephrine and endorphins) often referred to as "modulators", it is still difficult to classify these agents in all cases. Thus, in most central targets where NE-fibers are known to terminate, the synaptic actions of NE appear to have properties of both a neuromodulator and a neurotransmitter. Although much more research needs to be pursued, the opioid peptides may be neuromodulators for some neurons (spinal cord neurons) and neurotransmitters for others (myenteric plexus and spinal cord neurons). It may be that classification of such peptide agonists will need to be done on a cell-by-cell basis, with the endogenous peptides subserving a multi-faceted role in central and peripheral neuronal communication. As more and more endogenous ligands and transmitter-like substances are extracted from brain, it begins to appear that the language of neuronal communication is much richer than originally imagined from responses of spinal neurons to the fast-acting classical neurotransmitters. Indeed, it may evolve that the "deviant" forms of communication or transmission are more the rule than the exception. In the final analysis, each neurotransmitter may possess its own "fingerprint" of holistic actions attesting to the unique individuality of neuron types and their neurotransmitters. Such individualities might be expected to accomplish more sophisticated integrative operations, and hence behaviors, than could simple rapid "yes" or "no" messages.

Acetylcholine↗
PubMed1979

Chronic treatment with lithium or desipramine alters discharge frequency and norepinephrine responsiveness of cerebellar Purkinje cells.

Cerebellar Purkinje cells were studied by electrophysiological techniques in rats treated chronically with either desipramine (DMI) or lithium chloride given intragastrically. A striking decrement occurred in discharge frequencies of simple spikes and climbing fiber bursts in both groups of animals, similar to the depression produced by iontophoresis of these agents. Chronic treatment with DMI markedly decreased responsiveness to iontophoretically applied norepinephrine (NE), whereas long-term LiCl therapy slightly enhanced response to NE; responses to gamma-aminobutyric acid were unchanged by these treatments. The inhibitory responses to locus ceruleus stimulation were unaffected by chronic LiCl treatment. The effects of these chronic treatments on responsiveness to NE are opposite to the effects these same drugs produce when administered by acute iontophoresis to single cells: DMI then potentiates and LiCl antagonizes noradrenergic responses. These results provide electrophysiological evidence for reciprocal adaptive changes in NE sensitivity, supporting results of biochemical studies.

Animals↗
PubMed1979

Iontophoresis of Li+ antagonizes noradrenergic synaptic inhibition of rat cerebellar Purkinje cells.

Li salts provide effective therapy for manic-depressive psychosis, but the site and mechanism of this effect are not known. We have tested the ability of Li, applied by microiontophoresis, to modify the responsiveness of rat cerebellar Purkinje neurons to iontophoretic applications of norepinephrine and gamma-aminobutyrate and to the inhibition produced by stimulation of the noradrenergic ceruleo-cerebellar pathway. As previously reported for rat hippocampal neurons, acute exposure to Li produces selective, reversible antagonism of the effects of norepinephrine and the noradrenergic pathway but does not affect inhibitory actions of gamma-aminobutyrate. Collectively, these selective antagonisms of noradrenergic sympatic inhibitions in the cerebellum and hippocampus may indicate a general effect of Li suitable for extended observations in rats exposed to Li for the chronic periods needed to achieve therapeutic effects in man.

Animals↗
PubMed1977

Axonal transport of organelles visualized by light microscopy: cinemicrographic and computer analysis.

Rapid movements of intra-axonal organelles in acutely isolated single myelinated fibers from bullfrog sciatic nerve were visualized by dark-field microscopy. The movements were recorded by cinemicrography, and analyzed by computer-based methods. The movements are saltatory and bidirectional, but each particle moves mainly in a single direction. For more than 90% of the particles, the predominant movement direction is retrograde, i.e. toward the cell body. Quantitative measurements on a variety of parameters of the organelle movements are presented. Different particles in the same axon show a broad range of mean speeds. The average mean speed of movement in the retrograde direction at 28 degrees C was 1.08 micrometer/sec (S.D. - 0.41), equivalent to an axonal transport rate of 93 mm/day. Disperse distributions were also found for other parameters such as the instantaneous velocities of individual particles. Quantal velocities, periodic movement patterns, and specific 'channels' were not detected. When the data from a population of particles is treated statistically, the average mean speed, the distribution of velocities, and other statistical parameters are found to be similar in different axons studied at the same temperature. Direct microscopical observation of axonal organelle movement is a technique which provides information about axonal transport which is different from and complementary to that obtained from enzyme accumulation of radioactive tracer methods.

Animals↗
PubMed1977

Neuronal actions of endorphins and enkephalins among brain regions: a comparative microiontophoretic study.

The brain peptides alpha- and beta-endorphin, leucine- and methionine-enkephalin, as well as the opiate normorphine, have been evaluated by microiontophoresis for their effects on neuronal activity in several regions of the rat brain. In cerebral cortex, brainstem, caudate nucleus, and thalamus, most responsive cells were inhibited by the peptides and by normorphine, while in hippocampus all responsive cells were excited. Both inhibitory and excitatory responses were blocked by the narcotic antagonist naloxone. Occurrence of responsive cells encountered in a particular region was loosely correlated with density of stereospecific opiate binding sites as reported by others. These results are consistent with the hypothesis that the endorphins and enkephalins may represent a new class of central neurotransmitters; among other functions, these peptides may play a role in the regulation of behavior and the expression of psychopharmacological agents such as the opiate alkaloids.

Animals↗
PubMed1976

Electrophysiology of Purkinje neurons in the weaver mouse: iontophoresis of neurotransmitters and cyclic nucleotides, and stimulation of the nucleus locus coeruleus.

We compared the Purkinje cells of adult normal and weaver mutant (wv/wv) mice by iontophoretic and electrophysiological tests. Although weaver Purkinje cells fire spontaneously at a rate (38 Hz) similar to normal mouse neurons (40 Hz), several abnormalities of firing were seen: high frequency bursts of single (simple) spikes occurred in 5-10-sec episodes in 38% of weaver cells, compared to 8% in normal mice; spontaneous complex spikes (climbing fiber-like burst responses) occurred in several different forms in a given Purkinje cell. As in normal mice and rats, the spontaneous single spike activity is readily depressed by electrical stimulation of the locus coeruleus, the presumed source of a dense noradrenergic plexus in the weaver cerebellar cortex. In a preliminary experiment the adrenergic blocking agent, fluphenazine, antagonized the responses to locus coeruleus stimulation. Iontophoresis of norepinephrine (NE), GABA and serotonin (5-HT) also uniformly depressed Purkinje cell single spike activity in all normal and weaver mice; cyclic AMP depressed 55% of normal and 70% of weaver Purkinje cells. Glutamate was always excitatory. The only qualitative difference was seen with acetylcholine, which was mostly inhibitory in normal mouse, but increased the firing rate in 42% of weaver Purkinje neurons. Cyclic GMP was predominantly excitatory in both types. Thus, despite the absence of parallel fibers, weaver Purkinje neurons grossly resemble normal Purkinje cells electrophysiologically as well as morphologically. Since several sites of indirect presynaptic actions are eliminated in weaver, our results further substantiate the direct post-synaptic inhibitory nature of GABA, 5-HT and NE, and the noradrenergic pathway from locus coeruleus to Purkinje cells. Similarly, consistent inhibitory responses to cyclic AMP in the weaver support the previously hypothesized role of cyclic AMP in the post-synaptic inhibitory response to NE.

Acetylcholine↗
PubMed1975

Analogs of cyclic adenosine monophosphate: correlation of inhibition of Purkinje Neurons with Protein Kinase Activation.

Cyclic adenosine monophosphate (cyclic AMP) and 11 derivatives were applied to rat cerebellar Purkinje cells by iontophoresis. Cyclic AMP inhibited 63 percent of the cells, while the 8-parachlorophenylthio- and 8-benzylthio- analogs of cyclin AMP inhibited the spontaneous firing of 92 and 89 percent of cells, respectively. The ability of the 11 analogs to inhibit neuronal firing correlated ( r= + .78) with their reported potency in activating cyclic AMP-dependent protein kinase. These results extend previous studies, pointing to the mediation by cyclic AMP of the noradrenergic inhibition of Purkinje neurons, and provide new physiological evidence that protein phosphorylation is a major step in the action of cyclic AMP.

Action Potentials↗
PubMed1975

Characteristics of the release of adenosine 3':5'-monophosphate from micropipets by microiontophoresis.

The transfer number for radio-labelled cyclic AMP released from microiontophoretic pipets into brain pieces was determined for a large number of samples by radioassay. Release of cyclic AMP was linearly related to both iontophoretic current intensity and time as predicted by Faraday's Law. The results revealed that cyclic AMP has a rather low transfer number. In addition, an unusually large amount of variation of release, both within and among pipets was found under a variety of times and currents. The cause of the variation is not known but could be due to the unusual structure of the cyclic AMP molecule and the fact that it must be iontophoresed as a negative ion. These characteristics of cyclic AMP release may contribute to the difficulty in obtaining positive responses from appropriate neuronal target cells in vivo.

Animals↗