Simple models including energy and spike constraints reproduce complex activity patterns and metabolic disruptions

In this work, we introduce new phenomenological neuronal models (eLIF and mAdExp) that account for energy supply and demand in the cell as well as the inactivation of spike generation how these interact with subthreshold and spiking dynamics. Including these constraints, the new models reproduce a broad range of biologically-relevant behaviors that are identified to be crucial in many neurological disorders, but were not captured by commonly used phenomenological models. Because of their low dimensionality eLIF and mAdExp open the possibility of future large-scale simulations for more realistic studies of brain circuits involved in neuronal disorders. The new models enable both more accurate modeling and the possibility to study energy-associated disorders over the whole time-course of disease progression instead of only comparing the initially healthy status with the final diseased state. These models, therefore, provide new theoretical and computational methods to assess the opportunities of early diagnostics and the potential of energy-centered approaches to improve therapies.     

Removal of sodium inactivation and block of sodium channels by chloramine-T in crayfish and squid giant axons.

Modification of sodium channels by chloramine-T was examined in voltage clamped internally perfused crayfish and squid giant axons using the double sucrose gap and axial wire technique, respectively. Freshly prepared chloramine-T solution exerted two major actions on sodium channels: (a) an irreversible removal of the fast Na inactivation, and (b) a reversible block of the Na current. Both effects were observed when chloramine-T was applied internally or externally (5-10 mM) to axons. The first effect was studied in crayfish axons. We found that the removal of the fast Na inactivation did not depend on the states of the channel since the channel could be modified by chloramine-T at holding potential (from -80 to -100 mV) or at depolarized potential of -30 mV. After removal of fast Na inactivation, the slow inactivation mechanism was still present, and more channels could undergo slow inactivation. This result indicates that in crayfish axons the transition through the fast inactivated state is not a prerequisite for the slow inactivation to occur. During chloramine-T treatment, a distinct blocking phase occurred, which recovered upon washing out the drug. This second effect of chloramine-T was studied in detail in squid axons. After 24 h, chloramine-T solution lost its ability to remove fast inactivation but retained its blocking action. After removal of the fast Na inactivation, both fresh and aged chloramine-T solutions blocked the Na currents with a similar potency and in a voltage-dependent manner, being more pronounced at lower depolarizing potentials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Several nodulins of soybean share structural domains but differ in their subcellular locations.

Four soybean cDNA nodule-specific clones encoding nodulin-23, -26b, -27 and -44 were observed to cross-hybridize under low stringency conditions. Nucleotide sequence analysis revealed that the cDNAs contain three distinct domains: two domains with 70 to 95% homology separated by a third domain unique to each cDNA. Despite a number of nucleotide insertions and deletions, the protein sequences are conserved in the two domains which correlate with the homologous nucleotide domains. The amino terminal domain of each nodulin contains putative signal sequences for membrane translocation, although only two (nodulin-23 and -44) meet all the criteria for a functional signal. Immuno-precipitation of hybrid-release translation products of the four cDNAs revealed that nodulin-23 is associated with the peribacteroid membrane while nodulin-27 is in the cytoplasmic fraction of the nodule. These four nodulins are members of a diverse family with conserved structural features and the genes encoding them appear to have recently evolved from a common ancestor.     

Nodulin-26, a peribacteroid membrane nodulin is expressed independently of the development of the peribacteroid compartment.

The peribacteroid membrane (pbm) of root nodules is derived from the plant cell plasma membrane but contains in addition several nodule-specific host proteins (nodulins). Antibodies raised against purified pbm of soybean were used to immunoprecipitate polysomes to isolate an RNA fraction that served as a template for the synthesis of a cDNA probe for screening a nodule-specific cDNA library. Clone p1B1 was found to encode a 26.5 kDa polypeptide (nodulin-26) which is immunoprecipitable specifically with the anti-pbm serum. Nodulin-26 has features of a transmembrane protein and its structure differs from that of nodulin-24 which appears to be a surface protein of pbm. The expression of these two pbm nodulins was examined in nodules induced by Bradyrhizobium japonicum Tn5 mutants that arrest nodule development at different stages of pbm biosynthesis. Nodules that do not show release of bacteria from the infection thread express nodulin-24 at a very low level. In contrast, the expression of nodulin-26 occurs fully in nodules that form infection threads only and is not affected by the release of bacteria from the threads.     

Ectomycorrhizal colonization on black spruce and jack pine seedlings outplanted in reforestation sites

Six-week-old, mycorrhiza-free, bareroot jack pine and black spruce seedlings were outplanted in ten reforestation sites, situated between 45–48° latitude N and 69–74° longitude W, within the province of Quebec, representing diverse operational forestry disturbances and ecological conditions. Two months after outplanting, root systems of black spruce seedlings had fewer mycorrhizae than those of jack pine seedlings. Ectomycorrhizal colonization on black spruce seedlings did not vary significantly with the reforestation site. Percent mycorrhizal colonization for these seedlings was positively correlated with seedling dry weight while with the jack pine seedlings, mycorrhizal colonization varied significantly with the outplanting site and there was no correlation between mycorrhizal formation and seedling dry weight. Multiple linear regressions showed pH to be a determinant soil factor for mycorrhizal colonization for the two species. Drainage was the other influential factor affecting colonization of black spruce while organic matter accumulation was more important for jack pine. Inoculation with selected ectomycorrhizal fungi could be more important for black spruce than for jack pine seedlings.     

In vitro study of newborn rat brain maturation: implication for sudden infant death syndrome.

We have used slice preparation from newborn rats to study the development of the nucleus tractus solitarius neuronal network and brain intracellular phosphorus metabolites. As shown previously on adults, the newborn preparation retains local excitatory and inhibitory synaptic connections and enables study of intrinsic electrical properties in the nucleus tractus solitarius. Electrophysiological investigation of inhibitory synaptic transmission demonstrated a maturational step at days 4-6 after birth. Nuclear magnetic resonance spectroscopy of brain slices revealed a metabolic maturation between postnatal days 11 and 17. Results emphasize the differential maturation steps during the postnatal development of rat central nervous system. Possibly, Sudden Infant Death Syndrome may result from the abnormal timing in the occurrence of these steps.     

Divergent pharmacological responses to two calmodulin inhibitors, chlorpromazine and W-7, in rat pancreatic acinar cells

The possible role of calmodulin in exocytotic secretion is supported by the presence of this calcium-binding protein in secretory cells, and by the antisecretory effects in intact secretory cells of substances which can antagonize calmodulin-stimulated enzymes in broken cell preparations. In this study, two in vitro calmodulin antagonists, W-7 and chlorpromazine, were found to produce both similar and different pharmacological effects on the secretory process in rat exocrine pancreas. Both substances blocked amylase secretion in response to carbachol or cholecystokinin octapeptide, but only chlorpromazine inhibited the ability of carbachol to stimulate 45Ca efflux from isotope-preloaded cells. Only W-7 could inhibit the secretory response to vasoactive intestinal peptide (VIP); but both W-7 and chlorpromazine were equipotent partial antagonists of VIP-stimulated cyclic AMP synthesis. Chlorpromazine increased the secretory response to melittin but W-7 did not. The divergence in biological responsiveness to W-7 and chlorpromazine makes it difficult to extrapolate the in vitro effects of these agents to similar actions in intact cell systems.