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Co-variation of ionic conductances supports phase maintenance in stomatogastric neurons.

ABSTRACT: Neuronal networks produce reliable functional output throughout the lifespan of an animal despite ceaseless molecular turnover and a constantly changing environment. Central pattern generators, such as those of the crustacean stomatogastric ganglion (STG), are able to robustly maintain their functionality over a wide range of burst periods. Previous experimental work involving extracellular recordings of the pyloric pattern of the STG has demonstrated that as the burst period varies, the inter-neuronal delays are altered proportionally, resulting in burst phases that are roughly invariant. The question whether spike delays within bursts are also proportional to pyloric period has not been explored in detail. The mechanism by which the pyloric neurons accomplish phase maintenance is currently not obvious. Previous studies suggest that the co-regulation of certain ion channel properties may play a role in governing neuronal activity. Here, we observed in long-term recordings of the pyloric rhythm that spike delays can vary proportionally with burst period, so that spike phase is maintained. We then used a conductance-based model neuron to determine whether co-varying ionic membrane conductances results in neural output that emulates the experimentally observed phenomenon of spike phase maintenance. Next, we utilized a model neuron database to determine whether conductance correlations exist in model neuron populations with highly maintained spike phases. We found that co-varying certain conductances, including the sodium and transient calcium conductance pair, causes the model neuron to maintain a specific spike phase pattern. Results indicate a possible relationship between conductance co-regulation and phase maintenance in STG neurons.

SUBMITTER: Soofi W

PROVIDER: S-EPMC3394871 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Co-variation of ionic conductances supports phase maintenance in stomatogastric neurons.

Soofi Wafa W Archila Santiago S Prinz Astrid A AA

Journal of computational neuroscience 20111203 1

Neuronal networks produce reliable functional output throughout the lifespan of an animal despite ceaseless molecular turnover and a constantly changing environment. Central pattern generators, such as those of the crustacean stomatogastric ganglion (STG), are able to robustly maintain their functionality over a wide range of burst periods. Previous experimental work involving extracellular recordings of the pyloric pattern of the STG has demonstrated that as the burst period varies, the inter-n ...[more]

PMID: 22134522

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Project description:Polyelectrolytes of opposite charge in aqueous solution can undergo a liquid-liquid phase separation known as complex coacervation. Complex coacervation of ampholytic proteins with oppositely charged polyelectrolytes is of increasing interest as it results in a protein rich phase that has potential applications in protein therapeutics, protein purification, and biocatalysis. However, many globular proteins do not phase separate when mixed with an oppositely charged polyelectrolyte, and those that do phase separate do so over narrow concentration, pH, and ionic strength ranges. The protein design factors that govern complex coacervation under varying conditions are still relatively unexplored. Recent work indicates that proteins with an intrinsically disordered region, a higher net charge, or a patch of charged residues are more likely to undergo a phase transition. Based on these design parameters, polyionic coacervation tags were designed and assessed for their ability to promote protein complex coacervation with oppositely charged polyelectrolytes. The phase behavior of a panel of engineered proteins was evaluated with the strong polycation poly(4-vinyl N-methyl pyridinium iodide). Proteins containing the ionic tags formed liquid coacervate droplets, while isotropically charged protein variants formed solid precipitates. The ionic tags also promoted phase separation at higher salt concentrations than an isotropic distribution of charge on the protein surface. The salt dependence of the protein complex coacervation could be predicted independently for tagged or isotropic variants by the ratio of negative-to-positive residues on the proteins and universally by calculating the distance between like charges. The addition of just a six residue polyionic tag generated a globular protein capable of liquid-liquid phase separation at physiological pH and ionic strength. This model system has provided the initial demonstration that short, ionic polypeptide sequences (6-18 amino acids) can drive the liquid-liquid phase separation of globular proteins.

Dataset Information

Co-variation of ionic conductances supports phase maintenance in stomatogastric neurons.

Publications

Co-variation of ionic conductances supports phase maintenance in stomatogastric neurons.

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