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In JoVE (2)
- Homarus americanus Stomatogastric nervsystemet Dissection
- Gross Dissection i magen av Hummer, Homarus americanus
Other Publications (6)
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Articles by Anne-Elise Tobin in JoVE
JoVE General
Homarus americanus Stomatogastric nervsystemet Dissection
Volen Center for Complex Systems, Brandeis
Vi beskriver den fina dissekering av stomatogastric nervsystemet från magen av den amerikanska hummern (
JoVE General
Gross Dissection i magen av Hummer, Homarus americanus
Volen Center for Complex Systems, Brandeis
Vi beskriver de grova dissektion i magen av den amerikanska hummern (
Other articles by Anne-Elise Tobin on PubMed
Myomodulin Increases Ih and Inhibits the NA/K Pump to Modulate Bursting in Leech Heart Interneurons
In the medicinal leech, a rhythmically active 14-interneuron network composes the central pattern generator for heartbeat. In two segmental ganglia, bilateral pairs of reciprocally inhibitory heart interneurons (oscillator interneurons) produce a rhythm of alternating bursts of action potentials that paces activity in the pattern-generating network. The neuropeptide myomodulin decreases the period of this bursting and increases the intraburst spike frequency when applied to isolated ganglia containing these oscillator interneurons. Myomodulin also decreases period, increases spike frequency, and increases the robustness of endogenous bursting in synaptically isolated (with bicuculline) oscillator interneurons. In voltage-clamp experiments using hyperpolarizing ramps, we identify an increase in membrane conductance elicited by myomodulin with the properties of a hyperpolarization-activated current. Voltage steps confirm that myomodulin indeed increases the maximum conductance of the hyperpolarization-activated current I(h). In similar experiments using Cs(+) to block I(h), we demonstrate that myomodulin also causes a steady offset in the ramp current that is not associated with an increase in conductance. This current offset is blocked by ouabain, indicating that myomodulin inhibits the Na/K pump. In current-clamp experiments, when I(h) is blocked with Cs(+), myomodulin decreases period and increases spike frequency of alternating bursting in synaptically connected oscillator interneurons, suggesting that inhibiting the Na/K pump modulates these burst characteristics. These observations indicate that myomodulin decreases period and increases spike frequency of endogenous bursting in synaptically isolated oscillator heart interneurons and alternating bursting of reciprocally inhibitory pairs of interneurons, at least in part, by increasing I(h) and by decreasing the Na/K pump.
Creation and Reduction of a Morphologically Detailed Model of a Leech Heart Interneuron
Conductance-based neuron models aid in understanding the role intrinsic and synaptic currents play in producing neuronal activity. Incorporating morphological detail into a model allows for additional analysis of nonhomogeneous distributions of active and synaptic conductances, as well as spatial segregation of electrical events. We developed a morphologically detailed "Full Model" of a leech heart interneuron that replicates reasonably well intracellular recordings from these interneurons. However, it constitutes hundreds of compartments, each increasing parameter space and simulation time. To reduce the number of compartments of the Full Model, while preserving conductance densities and distributions, its compartments were grouped into functional groups that each share identical conductance densities. Each functional group was sequentially reduced to one or two compartments, preserving surface area, conductance densities, and its contribution to input resistance. As a result, the input resistance and membrane time constant were preserved. The axial resistances of several compartments were rescaled to match the amplitude of synaptic currents and low-threshold calcium currents and the shape of action potentials to those in the Full Model. This reduced model, with intrinsic conductances, matched the activity of the Full Model for a variety of simulated current-clamp and voltage-clamp data. Because surface area and conductance distribution of the functional groups of the Full Model were maintained, parameter changes introduced into the reduced model can be directly translated to the Full Model. Thus our computationally efficient reduced morphology model can be used as a tool for exploring the parameter space of the Full Model and in network simulations.
Endogenous and Half-center Bursting in Morphologically Inspired Models of Leech Heart Interneurons
Based on a detailed morphology "Full Model" of a leech heart interneuron, we previously developed a computationally efficient, morphologically inspired "Reduced Model" to expedite tuning the model to produce endogenous bursting and alternating bursting when configured as a half-center oscillator (paired with reciprocally inhibitory synapses). To find conductance density distributions that produce endogenous bursting, we implemented a genetic algorithm automated parameter search. With multiple searches, we found eight parameter sets that produced endogenous bursting in the Reduced Model. When these parameter sets were applied to the Full Model, all produced endogenous bursting, although when the simulation time was extended from 80 to 300 s, only four parameter sets produced sustained bursting in the Reduced Models. All parameter sets produced alternating half-center bursting in the Reduced and Full Models throughout the entire 300 s. When conductance amplitudes were systematically varied for each of the four sustained burster sets, the effects on bursting activity differed, both for the same parameter set in the Reduced and Full Models and for different parameter sets with the same level of morphological detail. This implies that morphological detail can affect burst activity and that these parameter sets may represent different mechanisms for burst generation and/or regulation. We also tested the models with parameter variations that correspond to experimental manipulations. We conclude that, whereas similar output can be achieved with multiple different parameter sets, perturbations such as conductance variations can highlight differences. Additionally, this work demonstrates both the utility and limitations of using simplified models to represent more morphologically accurate models.
How Tightly Tuned Are Network Parameters? Insight from Computational and Experimental Studies in Small Rhythmic Motor Networks
We describe theoretical and experimental studies that demonstrate that a given pattern of neuronal activity can be produced by variable sets of underlying conductances. Experimental work demonstrates that individual identified neurons in different animals may show variations as large as 2-5 fold in the conductance densities of specific ion channels. Theoretical work shows that models with this range of variation in many of their maximal conductances can produce similar activity. Together, these observations suggest that neurons and networks may be less tightly tuned than previously thought. Consequently, we argue that instead of attempting to construct single canonical models of neuronal function, it might be more useful to construct and analyze large families of models that give similar behavior.
Correlations in Ion Channel MRNA in Rhythmically Active Neurons
To what extent do identified neurons from different animals vary in their expression of ion channel genes? In neurons of the same type, is ion channel expression highly variable and/or is there any relationship between ion channel expression that is conserved?
Coregulation of Ion Channel Conductances Preserves Output in a Computational Model of a Crustacean Cardiac Motor Neuron
Similar activity patterns at both neuron and network levels can arise from different combinations of membrane and synaptic conductance values. A strategy by which neurons may preserve their electrical output is via cell type-dependent balances of inward and outward currents. Measurements of mRNA transcripts that encode ion channel proteins within motor neurons in the crustacean cardiac ganglion recently revealed correlations between certain channel types. To determine whether balances of intrinsic currents potentially resulting from such correlations preserve certain electrical cell outputs, we developed a nominal biophysical model of the crustacean cardiac ganglion using biological data. Predictions from the nominal model showed that coregulation of ionic currents may preserve the key characteristics of motor neuron activity. We then developed a methodology of sampling a multidimensional parameter space to select an appropriate model set for meaningful comparison with variations in correlations seen in biological datasets.
