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S C Landis

Publications and source records attributed to S C Landis.

103 records · Page 6Linked to original sources

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↗

Rat sympathetic neurons and cardiac myocytes developing in microcultures: correlation of the fine structure of endings with neurotransmitter function in single neurons.

Microcultures containing single sympathetic principal neurons and small numbers of dissociated heart myocytes were prepared from newborn rats. After the transmitter properties of the neuron were studied by electrophysiological experiments, the microculture was examined with the electron microscope. Single neurons of either putative cholinergic or putative adrenergic character made morphological synapses on themselves (autapses), although only cholinargic autapses were detected electrophysiologically. Numerous axonal varicosities were present adjacent to the myocytes but no synaptic specializations were evident. After permanganate fixation to localize endogenous norepinephrine, the endings of neurons which appeared to secrete catecholamines contained many small granular vesicles, while the endings of neurons which appeared to secrete acetylcholine contained none. The endings of neurons which apparently secreted both catecholamines and acetylcholine contained only occasional small granular vesicles.

Acetylcholine↗

Catecholamines in mutant mouse cerebellum: fluorescence microscopic and chemical studies.

Catecholamine-containing fibers have been examined in the cerebella of normal and hypocerebellar mutant mice using Falck-Hillarp and glyoxylic acid histofluorescence techniques. The amounts of norepinephrine and dopamine were also determined chemically in the same mutants. Green fluorescent fibers in cerebella of normal mice are similar in size and distribution to those described in the rat. Weanling and adult weaver, reeler and staggerer mice all manifest greatly increased specific catecholamine fluorescence per unit area in cerebellar cortex, but the patterns of fluorescent fibers are distinctive. In weaver, the fibers are of normal diameter, surround Purkinje cell bodies and appear to climb along major dendrites. In reeler, similar fibers form a plexus around cortical and non-cortical Purkinje cells; relatively normal fluorescent fiber patterns are present in well-organized cortical regions, while stouter disoriented fibers course through the shallow molecular layer in disorganized regions. Staggerer cerebellar cortex exhibits the greatest fluorescence with most terminals appearing as matted tangles adjacent cell bodies. Clearly defined fibers, however, can be distinguished in the molecular layer running perpendicular to the pia or for long distances in the coronal plane parallel to the pia. The major catecholamine determined chemically is norepinephrine. Reeler cerebella contain normal absolute levels and a doubled concentration of norepinephrine. In contrast, and despite the fluorescence findings, the total norepinephrine content of weaver and staggerer cerebella is significantly reduced and concentrations are not significantly different from normal.

Animals↗

Histochemical demonstration of mitochondrial dehydrogenases in developing normal and nervous mutant mouse Purkinje cells.

The mouse mutation nervous (nr), expressed as a recessive, causes a morphologic change in cerebellar Purkinje cell perikaryonal mitochondria during the 2nd postnatal week which is followed by the selective degeneration of most Purkinje cells. In the present study, mitochondrial dehydrogenase activities (succinic acid dehydrogenase, lactic acid dehydrogenase, malic acid dehydrogenase, reduced diphosphopyridine nucleotide diaphorase and succinic semialdehyde dehyrogenase) are found by light microscopy to be similar in the perikarya of normal and nervous Purkinje cells until after mitochondrial rounding has begun to occur, but then staining increases markedly in nervous. Although only a small fraction of mitochondrial functions were examined, those enzymes assayed were present and competent. In a sense, the only mitochondrial abnormalities demonstrated thus far in nervous Purkinje cells are their unusual shape and probable loss of motility.

Aging↗

The axostyle of Saccinobaculus. I. Structure of the organism and its microtubule bundle.

The axostyle of the flagellate Saccinobaculus is a motile ribbon composed of microtubules, cross-bridged to form interconnected rows. We find a centriole-related row of dark-staining tubules near the nucleus at the anterior end of the axostyle. Other tubule rows bind parallel to this primary row, acquire ordered relationships, and become the tubules of the axostyle proper. The number of tubule rows is constant in Saccinobaculus lata from the region near the nucleus to within a few micrometers of the posterior tip of the cell. In Saccinobaculus ambloaxostylus a few tubule rows are added to the axostyle posterior to the nucleus, giving this axostyle a leaf spring construction. The tubules of S. lata are held in rows by links with a 140 A periodicity along the tubule axis; bridges between rows of tubules are also seen but are not apparently periodic. Each tubule in S. ambloaxostylus shows an axial periodicity of 150 A due to pairs of arms, one of which is always part of the intrarow link. Interrow bridges in this species run either from tubule to tubule or from tubule to the free arm, but as in S. lata they do not display an obvious axial periodicity. An average unit cell is presented for the axostyle of each species, and the relation of the intertubule links to the microtubule substructure is discussed.

Animals↗

Ultrastructural changes in the mitochondria of cerebellar Purkinje cells of nervous mutant mice.

The maturation of cerebellar Purkinje cells of normal and nervous (nr/nr) mutant mice has been studied by light and electron microscopy. In the mutant, 90% of Purkinje cells selectively degenerate between postnatal days 23 and 50. Losses are greater in lateral than medial regions. Other cerebellar neurons appear normal. The first morphological abnormality recognized is the presence of rounded mitochondria in perikarya of some Purkinje cells of the mutant at 9 days after birth. By 15 days, all nr/nr Purkinje cells contain spherical mitochondria and begin to deviate from the normal maturational sequence. Elaboration of the extensive dendritic tree halts midway and newly formed axon collateral fibers degenerate. In the perikaryon, the basal polysomal accumulation and climbing fiber-somatic spine synapses are sometimes abnormally retained. Cisternae of the Golgi apparatus and rough endoplasmic reticulum cease to form aligned stacks, and decrease in number, while polysomes dissociate into free ribosomes. These changes are progressive, culminating in cell death. Although every nr/nr Purkinje cell demonstrates spherical mitochondria, some cells survive the critical period, retain a near-normal complement of organelles, and reacquire normal-appearing mitochondria. The disorder appears intrinsic to Purkinje cells since all major classes of synapses were identified before cell death.

Animals↗