Search PubMed⌕ Search

Biomedical subjects

T A Christensen

Publications and source records attributed to T A Christensen.

29 records · Page 2Linked to original sources
PubMed1992

Inhibition of growth factor binding, Ca2+ signaling and cell growth by polysulfonated azo dyes related to the antitumor agent suramin.

The ability of the polysulfonated antitumor drug suramin and six related polysulfonated azo dyes to inhibit the cell growth, platelet-derived growth factor (PDGF)-receptor binding, and intracellular Ca2+ signaling of Swiss 3T3 fibroblasts was studied. Some of the azo dyes were more potent inhibitors of PDGF binding than was suramin. The concentration giving 50% inhibition (IC50) of PDGF binding was 0.5 microM for the most potent azo dye as compared with 10 microM for suramin. The azo dyes were generally more potent inhibitors of nonmitochondrial Ca2+ uptake and of inositol(1,4,5)trisphosphate-mediated Ca2+ release in permeabilized Swiss 3T3 cells than was suramin, and they were more potent inhibitors of PDGF-induced Ca2+ signaling in intact Swiss 3T3 cells. The azo dyes were only as effective as or less effective than suramin in inhibiting the growth of Swiss 3T3 cells, with IC50 values of between 74 and 361 microM being noted for the dyes as compared with 70 microM for suramin. The difference between the growth-inhibitory activity of the azo dyes and that of suramin could not be explained by metabolism of the compounds, which was not detectable in either Swiss 3T3 cells or human liver slice preparations. The results suggest that suramin and some of the azo dyes have actions on cell growth in addition to inhibition of growth factor binding and of Ca2+ signaling.

3T3 Cells↗
PubMed1992

The roles of local interneurons in the processing of olfactory information in the antennal lobes of the moth Manduca sexta.

The antennal lobe (AL) of the sphinx month Manduca sexta is characterized by a typically glomerular neuropil and two principal classes to neurons local interneurons and projection neurons. The somata of these neurons reside in defined neural cell-body groups in the AL, and the neurons exhibit characteristic patterns of innervation of the glomeruli. Evidence gathered to date indicates that individual antennal olfactory receptor-cell axons project to single glomeruli in the ipsilateral AL and make excitatory, apparently cholinergic synapses with neurites of AL neurons (usually local neurons) innervating the target glomeruli. Much has been learned about the physiology of the projection neurons, but only recently have the physiological properties and functions of the local interneurons been examined systematically through the use of intracellular recording and staining methods. Immunocytochemical studies have shown that most of the local interneurons contain GABA as well as one or more putative neuropeptides. Physiological, pharmacological, and biochemical experiments support the view that GABAergic local interneurons are responsible for inhibitory synaptic inputs to projection neurons that predominate in shaping the activity of projection neurons conveying synaptically processed olfactory information to higher-order centers in the protocerebrum.

Animals↗
PubMed1991

Functionally distinct subdivisions of the macroglomerular complex in the antennal lobe of the male sphinx moth Manduca sexta.

Each antennal lobe in the brain of a male moth has a distinctive neuropil structure, the macroglomerular complex (MGC), which is specialized for primary processing of information about the conspecific female sex-pheromone blend. Olfactory interneurons with dendritic arborizations in the MGC were examined by means of tandem intracellular recording and staining with Lucifer Yellow. Neurons that responded selectively to stimulation of the antenna with the major pheromone component, (E,Z)-10,12-hexadecadienal, had arborizations that were restricted to a toroidal subdivision (the "toroid") of the MGC. Similarly, neurons that responded selectively to antennal stimulation with (E,Z)-11,13-pentadecadienal, a more stable mimic of a second essential but chemically unstable pheromone component, (E,E,Z)-10,12,14-hexadecatrienal, had arborizations confined to a globular subdivision (the "cumulus") of the MGC situated more proximally to the antennal nerve input. One neuron that responded to both of these stimuli clearly had arborizations in both subdivisions of the MGC. These anatomically distinct subdivisions of the MGC thus appear also to be functionally separate regions of pheromone-processing neuropil.

Animals↗
PubMed1991

Innervation and neural regulation of the sex pheromone gland in female Heliothis moths.

Female Heliothis moths normally produce their species-specific male attractant (sex pheromone blend) during scotophase, and this production is stimulated by pheromone biosynthesis activating neuropeptide (PBAN), presumably carried in the hemolymph. Several lines of evidence indicate that the central nervous system plays another critical role in this regulation. Pheromone biosynthesis was induced during photophase by electrical stimulation of the ventral nerve cord or the peripheral nerves projecting from the terminal abdominal ganglion to the pheromone gland in the tip of the abdomen. Electron microscopy further revealed that axonal branches innervate the gland tissue. Nerve branches associated with pheromone gland cells are enwrapped in glia and contain dense-core vesicles, suggesting that the innervation of the gland might be neurosecretory. Finally, the biogenic monoamine octopamine was nearly as effective as purified Heliothis zea PBAN in stimulating pheromone biosynthesis when injected into intact females during mid-photophase. Furthermore, both octopamine and PBAN stimulated significant increases in the pheromone content of the glands in isolated abdomens lacking a ventral nerve cord but only when abdomens were treated at the onset of scotophase. These data suggest that the regulation of sex pheromone production in Heliothis is more complex than previously thought. Activation of the gland appears to be governed by both neural and hormonal mechanisms, and these control mechanisms depend on photoperiodic cues.

Animals↗
PubMed1987

GABA-mediated synaptic inhibition of projection neurons in the antennal lobes of the sphinx moth, Manduca sexta.

Responses of neurons in the antennal lobe (AL) of the moth Manduca sexta to stimulation of the ipsilateral antenna by odors consist of excitatory and inhibitory synaptic potentials. Stimulation of primary afferent fibers by electrical shock of the antennal nerve causes a characteristic IPSP-EPSP synaptic response in AL projection neurons. The IPSP in projection neurons reverses below the resting potential, is sensitive to changes in external and internal chloride concentration, and thus is apparently mediated by an increase in chloride conductance. The IPSP is reversibly blocked by 100 microM picrotoxin or bicuculline. Many AL neurons respond to application of GABA with a strong hyperpolarization and an inhibition of spontaneous spiking activity. GABA responses are associated with an increase in neuronal input conductance and a reversal potential below the resting potential. Application of GABA blocks inhibitory synaptic inputs and reduces or blocks excitatory inputs. EPSPs can be protected from depression by application of GABA. Muscimol, a GABA analog that mimics GABA responses at GABAA receptors but not at GABAB receptors in the vertebrate CNS, inhibits many AL neurons in the moth.

Animals↗
PubMed1987

Male-specific, sex pheromone-selective projection neurons in the antennal lobes of the moth Manduca sexta.

A subset of olfactory projection neurons in the brain of male Manduca sexta is described, and their role in sex pheromone information processing is examined. These neurons have extensive arborizations in the macroglomerular complex (MGC), a distinctive and sexually dimorphic area of neuropil in the antennal lobe (AL), to which the axons of two known classes of antennal pheromone receptors project. Each projection neuron sends an axon from the AL into the protocerebrum. Forty-one projection neurons were characterized according to their responses to electrical stimulation of the antennal nerve as well as olfactory stimulation of antennal receptors. All neurons exhibited strong selectivity for female sex pheromones. Other behaviorally relevant odors, such as plant volatiles, had no obvious effect on the activity of these neurons. Two broad physiological categories were found: cells that were excited by stimulation of the ipsilateral antenna with pheromones (29 out of 41), and cells that received a mixed input (inhibition and excitation) from pheromone pathways (12 out of 41). Of the cells in the first category, 13 out of 29 were equally excited in response to stimulation of the antenna with either the principal natural pheromone (bombykal) or a mimic of a second unidentified pheromone ('C-15') and were similarly excited by the natural pheromone blend. The remaining 16 out of 29 cells responded selectively, and in some cases, in a dose-dependent manner, to stimulation of the antenna with bombykal or C-15, but not both. Some of these neurons had dendritic arborizations restricted to only a portion of the MGC neuropil, whereas most had arborizations throughout the MGC. Of the cells in the second category, 9 out of 12 were excited by bombykal, inhibited by C-15, and showed a mixed response to the natural pheromone blend. For the other 3 out of 12 cells, the response polarity was reversed for the two chemically-identified odors. Two additional neurons, which were not tested with olfactory stimuli, were tonically inhibited in response to electrical stimulation of the ipsilateral antennal nerve. These observations suggest that some of the male-specific projection neurons may signal general pheromone-triggered arousal, whereas a smaller number can actively integrate inputs from the two know receptor classes (Bal- and C-15-selective) and may operate as 'mixture detectors' at this level of the olfactory subsystem that processes information about sex pheromones.

Animals↗
PubMed1986

Immunocytochemistry of GABA in the antennal lobes of the sphinx moth Manduca sexta.

We have prepared and characterized specific rabbit antisera against gamma-aminobutyric acid (GABA) coupled covalently to bovine serum albumin and keyhole-limpet hemocyanin. Using these antisera in immunocytochemical staining procedures, we have probed the antennal lobes and their afferent and efferent fiber tracts in the sphinx moth Manduca sexta for GABA-like immunoreactivity in order to map putatively GABAergic central neurons in the central antennal-sensory pathway. About 30% of the neuronal somata in the large lateral group of cell bodies in the antennal lobe are GABA-immunoreactive; cells in the medial and anterior groups of antennal-lobe cells did not exhibit GABA-like immunoreactivity. GABA-immunoreactive neurites had arborizations in all of the glomeruli in the antennal lobe. Double-labeling experiments involving tandem intracellular staining with Lucifer Yellow and immunocytochemical staining for GABA-like immunoreactivity demonstrated that at least some of the GABA-immunoreactive cells in the antennal lobe are amacrine local interneurons. Several fiber tracts that carry axons of antennal-lobe projection neurons exhibited GABA-immunoreactive fibers. Among the possibly GABA-containing projection neurons are several cells, with somata in the lateral group of the antennal lobe, that send their axons directly to the lateral protocerebrum.

Animals↗
PubMed1983

Presence of octopamine in firefly photomotor neurons.

Various tissues involved in producing luminescence in larval fireflies (Photuris versicolor) were examined for the presence of octopamine. These tissues included the terminal abdominal ganglion (A8) which innervates the paired lantern organs, the cell bodies of the photomotor neurons and the isolated larval lanterns. A previous study has identified the 4 motoneurons arising from A8 which bilaterally innervate the paired larval lanterns through symmetrical axons existing both sides of the ganglion. Individual photomotor neuron somata were isolated, pooled and found to contain about 0.03 pmol/soma giving an effective concentration of 2.8 mM octopamine. Significant amounts of octopamine were also found within the peripheral effector tissue. The presence of octopamine throughout the luminescence-producing pathway further supports the hypothesis that octopamine serves a neurotransmitter function in firefly bioluminescence. In this system, it appears that octopamine serves a more direct role as a neurotransmitter that that postulated for its modulatory and hormonal functions in other arthropod systems. Furthermore, the bioluminescent response of the larval firefly lantern provides a useful dynamic system to study the physiology, pharmacology and biochemistry of octopaminergic transmission.

Animals↗
PubMedDate not supplied

Morphometric modeling of olfactory circuits in the insect antennal lobe: I. Simulations of spiking local interneurons.

Inhibitory local interneurons (LNs) play a critical role in shaping the output of olfactory glomeruli in both the olfactory bulb of vertebrates and the antennal lobe of insects and other invertebrates. In order to examine how the complex geometry of LNs may affect signaling in the antennal lobe, we constructed detailed multi-compartmental models of single LNs from the sphinx moth, Manduca sexta, using morphometric data from confocal-microscopic images. Simulations clearly revealed a directionality in LNs that impeded the propagation of injected currents from the sub-micron-diameter glomerular dendrites toward the much larger-diameter integrating segment (IS) in the coarse neuropil. Furthermore, the addition of randomly-firing synapses distributed across the LN dendrites (simulating the noisy baseline activity of afferent input recorded from LNs in the odor-free state) led to a significant depolarization of the LN. Thus the background activity typically recorded from LNs in vivo could influence synaptic integration and spike transformation in LNs through voltage-dependent mechanisms. Other model manipulations showed that active currents inserted into the IS can help synchronize the activation of inhibitory synapses in glomeruli across the antennal lobe. These data, therefore, support experimental findings suggesting that spiking inhibitory LNs can operate as multifunctional units under different ambient odor conditions. At low odor intensities, (i.e. subthreshold for IS spiking), they participate in local, mostly intra-glomerular processing. When activated by elevated odor concentrations, however, the same neurons will fire overshooting action potentials, resulting in the spread of inhibition more globally across the antennal lobe. Modulation of the passive and active properties of LNs may, therefore, be a deciding factor in defining the multi-glomerular representations of odors in the brain.

Animals↗