Biology subjects

Marder, E.

Publications and source records attributed to Marder, E..

7 recordsLinked to original sources

bioRxiv2018

Visualization of the relative contributions of conductances in neuronal models with similar behavior and different conductance densities

Conductance-based models of neural activity produce large amounts of data that can be hard to visualize and interpret. Here we introduce two novel visualization methods to display the dynamics of the ionic currents, and to investigate how the contribution of each current changes in response to perturbation. We explored the solutions of a single compartment, conductance-based model of neural activity with seven voltage-gated ionic currents and a leak channel. We employed landscape optimization to find sets of maximal conductances that produce similar target activity and displayed the dynamics of the currents. We examined in detail six examples of a bursting model neuron that differ as much as 3-fold in the conductance densities of each of the 8 currents in the model. The maximal conductance of each current does not simply predict the importance of the current for neuronal dynamics. We then compared the effects of systematically reducing the conductances of each current for neuronal dynamics, and demonstrate that models that appear similar under starting conditions behave dramatically differently to the decreases in conductance densities. These examples provide heuristic insight into why individuals with similar behavior can nonetheless respond widely differently to perturbations.

neuroscience↗

bioRxiv2018

Xolotl: An Intuitive and Approachable Neuron and Network Simulator for Research and Teaching

Conductance-based models of neurons are used extensively in computational neuroscience. Working with these models can be challenging due to their high dimensionality and large number of parameters. Here, we present a neuron and network simulator built on a novel automatic type system that binds object-oriented code written in C++ to objects in MATLAB. Our approach builds on the tradition of uniting the speed of languages like C++ with the ease-of-use and feature-set of scientific programming languages like MATLAB. Xolotl allows for the creation and manipulation of hierarchical models with components that are named and searchable, permitting intuitive high-level programmatic control over all parts of the model. The simulators architecture allows for the interactive manipulation of any parameter in any model, and for visualizing the effects of changing that parameter immediately. Xolotl is fully featured with hundreds of ion channel models from the electrophysiological literature, and can be extended to include arbitrary conductances, synapses, and mechanisms. Several core features like bookmarking of parameters and automatic hashing of source code facilitate reproducible and auditable research. Its ease of use and rich visualization capabilities make it an attractive option in teaching environments. Finally, xolotl is written in a modular fashion, includes detailed tutorials and worked examples, and is freely available at https://github.com/sg-s/xolotl, enabling seamless integration into the workflows of other researchers.

neuroscience↗

bioRxiv2018

Two central pattern generators from the crab, Cancer borealis, respond robustly and differentially to extreme extracellular pH

Animals and their neuronal circuits must maintain function despite significant environmental fluctuations. The crab, Cancer borealis, experiences daily changes in ocean temperature and pH. Here, we describe the effects of extreme changes in extracellular pH - from pH 5.5 to 10.4 - on two central pattern generating networks, the stomatogastric and cardiac ganglia of C. borealis. Given that the physiological properties of ion channels are known to be sensitive to pH within the range tested, it is surprising that these rhythms generally remained robust from pH 6.1 to pH 8.8. Unexpectedly, the stomatogastric ganglion was more sensitive to acid while the cardiac ganglion was more sensitive to base. Considerable animal-to-animal variability was likely a consequence of similar network performance arising from variable sets of underlying conductances. Together, these results illustrate the potential difficulty in generalizing the effects of environmental perturbation across circuits, even within the same animal.\n\nAbbreviations

neuroscience↗

bioRxiv2018

Neuronal morphologies built for reliable physiology in a rhythmic motor circuit

The neurons of the crustacean stomatogastric ganglion (STG) exhibit highly-conserved firing patterns, voltage waveforms, and circuit functions despite quantifiable animal-to-animal variability in their neuronal morphologies. In recent work, we showed that one neuron type, the Gastric Mill (GM) neuron, is electrotonically compact and operates much like a single compartment, despite having thousands of branch points and a total cable length on the order of 10 mm. Here, we explore how STG neurite morphology shapes voltage signal propagation and summation in four STG neuron types. We use focal glutamate photo-uncaging in tandem with somatic intracellular recordings to examine passive electrotonic structure and voltage signal summation in the GM neuron and three additional STG neuron types: Lateral Pyloric (LP), Ventricular Dilator (VD), and Pyloric Dilator (PD) neurons. In each neuron, we measured the amplitudes and apparent reversal potentials (Erevs) of inhibitory responses evoked with focal glutamate photo-uncaging at more than 20 sites varying in their distance (100-800 m) from the somatic recording site in the presence of TTX. Apparent Erevs were relatively invariant (mean CVs = 0.04, 0.06, 0.05, and 0.08 for 5-6 GM, LP, PD, VD neurons, respectively), suggesting that all four neuron types are similarly electrotonically uniform and compact. We then characterized the directional sensitivity and arithmetic of voltage summation (with fast sequential activation of 4-6 sites) in individual STG neurites. All four neuron types showed no directional bias in voltage signal summation and linear voltage summation. We motivate these experiments with a proof-of-concept computational model that suggests the immense tapering of STG neurite diameters: from 10-20 m to sub-micron diameters at the terminal tips, may explain the uniform electrotonic structures experimentally observed and contribute to the robust nature of this central pattern-generating circuit.

neuroscience↗

bioRxiv2018

In vivo Effects of Temperature on the Heart and Pyloric Rhythms in the Crab, Cancer borealis

Summary StatementTemperature elevation increases the frequency of the heart and pyloric rhythms of the crab, Cancer borealis, but the heart rhythm has a higher critical temperature than the pyloric rhythm.\n\nAbstractThe heart and pyloric rhythms of crustaceans have been studied separately and extensively over many years. Local and hormonal neuromodulation and sensory inputs onto these central pattern generating circuits play a significant role in the animals responses to perturbations, but are usually lost or removed during in vitro studies. To examine simultaneously the in vivo motor output of the heart and pyloric rhythms, we used photoplethysmography (PPG). In the population measured (n = 49), the heart rhythm frequencies ranged from 0.3-2.3 Hz. The pyloric rhythms varied from 0.2-1.6 Hz. During multiple hour-long recordings, many animals held at control temperature showed strong inhibitory bouts in which the heart decreased in frequency or become quiescent and the pyloric rhythm also decreased in frequency. Many animals show significant coherence in frequency between the rhythms at the frequency of the heart rhythm. We measured the simultaneous responses of the rhythms to temperature ramps by heating or cooling the saline bath while recording both the heart and pyloric muscle movements. Q10s, critical temperatures (temperatures at which function is compromised), and changes in frequency were calculated for each of the rhythms tested. The heart rhythm was more robust to high temperature than the pyloric rhythm.

neuroscience↗

bioRxiv2017

Regulation of Eag by calcium/calmodulin controls presynaptic excitability in Drosophila

Drosophila ether-a-go-go (eag) is the founding member of a large family of voltage-gated K+ channels, the KCNH family, which includes Kv10, 11 and 12, (Ganetzky et al. 1999). Concurrent binding of calcium/calmodulin (Ca2+/CaM) to N-and C-terminal sites inhibits mammalian EAG1 channels at sub-micromolar Ca2+ concentrations (Schonherr et al. 2000), likely by causing pore constriction (Whicher and MacKinnon 2016). Although the Drosophila EAG channel was believed to be Ca2+-insensitive (Schonherr et al. 2000), both the N-and C-terminal sites are conserved. Here we show that Drosophila EAG is inhibited by high Ca2+ concentrations that are only present at plasma membrane Ca2+ channel microdomains. To test the role of this regulation in vivo, we engineered mutations that block CaM-binding to the major C-terminal site of the endogenous eag locus, disrupting Ca2+-dependent inhibition. eag CaMBD mutants have reduced evoked release from larval motor neuron presynaptic terminals and show decreased Ca2+ influx in stimulated adult projection neuron presynaptic terminals, consistent with an increase in K+ conductance. These results are predicted by a conductance-based multi-compartment model of the presynaptic terminal in which some fraction of EAG is localized to the Ca2+ channel microdomains that control neurotransmitter release. The reduction of release in the larval neuromuscular junction drives a compensatory increase in motor neuron somatic excitability. This misregulation of synaptic and somatic excitability has consequences for systems-level processes and leads to defects in associative memory formation in adults.\n\nNew and NoteworthyRegulation of excitability is critical to tuning the nervous system for complex behaviors. We demonstrate here that the EAG family of voltage-gated K+ channels exhibit conserved gating by Ca2+/CaM. Disruption of this inhibition in Drosophila results in decreased evoked neurotransmitter release due to truncated Ca2+ influx in presynaptic terminals. In adults, disrupted Ca2+ dynamics cripples memory formation. These data demonstrate that the biophysical details of channels have important implications for cell function and behavior.

neuroscience↗

bioRxiv2017

Circuit robustness to temperature perturbation is altered by neuromodulators

In the ocean, the crab, Cancer borealis, is subject to daily and seasonal temperature changes. Previous work, done in the presence of descending modulatory inputs, had shown that the pyloric rhythm of the crab increases in frequency as temperature increases, but maintains its characteristic phase relationships until it \"crashes\" at extreme high temperatures. To study the interaction between neuromodulators and temperature perturbations, we studied the effects of temperature on preparations from which the descending modulatory inputs were removed. Under these conditions the pyloric rhythm was destabilized. We then studied the effects of temperature on preparations in the presence of oxotremorine, proctolin, and serotonin. Oxotremorine and proctolin enhanced the robustness of the pyloric rhythm, while serotonin made the rhythm less robust. These experiments reveal considerable animal-to-animal diversity in their crash stability, consistent with the interpretation that cryptic differences in many cell and network parameters are revealed by extreme perturbations.

neuroscience↗