Biomedical subjects

Robert J Butera

Publications and source records attributed to Robert J Butera.

13 recordsLinked to original sources

PubMed2006

A comparative analysis of multi-conductance neuronal models in silico.

We demonstrate that a previously presented flexible silicon-neuron architecture can implement three disparate conductance-based neuron models with both fast and slow dynamics. By exploiting the real-time nature of this physical implementation, we mapped the model dynamics across a large region of parameter space. We also found that two of these dynamically different models represent points in a contiguous bursting space that spans between the two models. By systematically varying the model parameters, we also found that multiple, diverse trajectories in parameter space connected the two canonical bursting points. In addition, we found that the combination of parameter values keeps the neuron in the bursting region. These findings demonstrate the usefulness of the silicon-neuron architecture as a neural-modeling tool and illustrate its versatility as a platform for a multi-behavioral neuron that resembles its living analog.

Animals↗

PubMed2006

Serotonergic enhancement of a 4-AP-sensitive current mediates the synaptic depression phase of spike timing-dependent neuromodulation.

The mechanism underlying spike timing-dependent neuromodulation (STDN) was investigated in the opisthobranch mollusc Tritonia diomedea. The serotonergic dorsal swim interneurons (DSIs) dynamically modulated the synaptic output of ventral swim interneuron B (VSI); immediately after DSI stimulation, there was a potentiation of VSI synaptic strength followed by a longer-lasting synaptic depression. The potentiation phase of STDN was unaffected by spike broadening produced by the potassium channel blocker 4-aminopyridine (4-AP). In contrast, the depression phase was eliminated by 4-AP. Bath-applied serotonin (5-HT) decreased VSI spike duration and increased the magnitude of the A-current (IA), a voltage-dependent, transient, outward current. 4-AP preferentially blocked IA and prevented the spike narrowing caused by 5-HT, uncovering the full extent of 5-HT-induced synaptic potentiation. A consistent correlation was observed between IA and spike duration, but the correlation between synaptic strength and spike duration differed between preparations. Conductance-based simulations showed that the magnitude of A-current conductance could affect spike duration and gave an estimation of the change needed to produce spike narrowing. An artificial IA introduced into the VSI in the presence of 4-AP by means of the dynamic-clamp technique restored spike duration and gave a further approximation of the magnitude of modulation needed for spike narrowing. Together, these results suggest a mechanism for STDN: the DSIs release 5-HT, which causes a spike duration-independent enhancement of synaptic strength and a longer-lasting enhancement of IA that narrows the VSI spike and hence decreases VSI synaptic strength. Thus, STDN arises from the dynamics of independent intracellular signaling events.

4-Aminopyridine↗

PubMed2005

Neuronal oscillators in aplysia californica that demonstrate weak coupling in vitro.

Networks of oscillators produce vital activity in diverse natural systems. The dynamics of these networks are frequently studied via computational models that assume weak coupling, yet this assumption has not been experimentally validated. We applied weak stimuli to neuronal oscillators in Aplysia californica and deconvolved infinitesimal phase response curves (IPRCs) that describe the phase response of a neuron. We show that these IPRCs reliably predict the phase response for weak stimuli, independent of the stimulus waveform used. These weak stimuli are in the range of normal synaptic activity for these neurons, suggesting that weak coupling is a likely mechanism.

Animals↗

PubMed2005

Oscillations in a simple neuromechanical system: underlying mechanisms.

A half-center neural oscillator was coupled to a simple mechanical system to study the closed-loop interactions between a central pattern generator and its effector muscles. After a review of the open-loop mechanisms that were previously introduced by Skinner et al. (1994), we extend their geometric approach and introduce four additional closed-loop mechanisms by the inclusion of an antagonistic muscle pair acting on a mass and connected to the half-center neural oscillator ipsilaterally. Two of the closed-loop mechanisms, mechanical release mechanisms, have close resemblance to open-loop release mechanisms whereas the latter two, afferent mechanisms, have a strong dependence on the mechanical properties of the system. The results also show that stable oscillations can emerge in the presence of sensory feedback even if the neural system is not oscillatory. Finally, the feasibility of the closed-loop mechanisms was shown by weakening the idealized assumptions of the synaptic and the feedback connections as well as the rapidity of the oscillations.

Animals↗

PubMed2005

Ionic current model of a hypoglossal motoneuron.

We have developed a single-compartment, electrophysiological, hypoglossal motoneuron (HM) model based primarily on experimental data from neonatal rat HMs. The model is able to reproduce the fine features of the HM action potential: the fast afterhyperpolarization, the afterdepolarization, and the medium-duration afterhyperpolarization (mAHP). The model also reproduces the repetitive firing properties seen in neonatal HMs and replicates the neuron's response to pharmacological experiments. The model was used to study the role of specific ionic currents in HM firing and how variations in the densities of these currents may account for age-dependent changes in excitability seen in HMs. By varying the density of a fast inactivating calcium current, the model alternates between accelerating and adapting firing patterns. Modeling the age-dependent increase in H current density accounts for the decrease in mAHP duration observed experimentally, but does not fully account for the decrease in input resistance. An increase in the density of the voltage-dependent potassium currents and the H current is required to account for the decrease in input resistance. These changes also account for the age-dependent decrease in action potential duration.

Action Potentials↗

PubMed2004

Analysis of real-time numerical integration methods applied to dynamic clamp experiments.

Real-time systems are frequently used as an experimental tool, whereby simulated models interact in real time with neurophysiological experiments. The most demanding of these techniques is known as the dynamic clamp, where simulated ion channel conductances are artificially injected into a neuron via intracellular electrodes for measurement and stimulation. Methodologies for implementing the numerical integration of the gating variables in real time typically employ first-order numerical methods, either Euler or exponential Euler (EE). EE is often used for rapidly integrating ion channel gating variables. We find via simulation studies that for small time steps, both methods are comparable, but at larger time steps, EE performs worse than Euler. We derive error bounds for both methods, and find that the error can be characterized in terms of two ratios: time step over time constant, and voltage measurement error over the slope factor of the steady-state activation curve of the voltage-dependent gating variable. These ratios reliably bound the simulation error and yield results consistent with the simulation analysis. Our bounds quantitatively illustrate how measurement error restricts the accuracy that can be obtained by using smaller step sizes. Finally, we demonstrate that Euler can be computed with identical computational efficiency as EE.

Action Potentials↗

PubMed2004

MRCI: a flexible real-time dynamic clamp system for electrophysiology experiments.

We present a real-time simulation system that enables modeled dynamical systems to interact with physical experimental systems, and is specifically aimed towards execution of the dynamic clamp protocol. Model reference current injection (MRCI) operates under Real-Time Linux (RT-Linux or RTL) and provides a simple equation-oriented language for describing dynamical system models. Features include scripting of commands to implement repeatable protocols, the ability to output pre-computed waveforms through any variable or parameter of the model, the means to conduct time measurements and assess the computational performance of the real-time system, and an installation program that installs the software and accompanying device drivers with minimal input from the user. Tested models operate as fast as 30 kHz, with actual maximum rates dependent on model complexity. We present sample models that exhibit the main features of the modeling language. Experiments demonstrate the abilities of the system by creating a hybrid network of real and simulated neurons, and playing a pre-defined synaptic waveform into a synaptic conductance variable. We conclude by introducing a waveform reconstruction technique that is useful for establishing the presence of significant experimental error in implementations of the dynamic clamp protocol.

Action Potentials↗

PubMed2004

Estimating action potential thresholds from neuronal time-series: new metrics and evaluation of methodologies.

The estimation of action potential thresholds is a subjective process, which we quantified by surveying experienced electrophysiologists via a software application that allowed them to select action potential thresholds from several presented neuronal time series. Independent of this survey, we derived two nonparametric techniques for automating the detection of an action potential threshold from the time-series of intracellular recordings. Both methods start with a phase-space representation of the action potential (dV/dt versus V). Method I detects the maximum slope in the phase space, while Method II detects the maximum second derivative in the phase space. These two methods, as well as five additional methods in the literature, were tested on three data sets representing a variety of action potential shapes, the same three datasets that were used in the electrophysiologist survey. The database of user responses was used to provide an external benchmark against which to statistically evaluate all seven methods. Method II, as well as the curvature-based Methods VI and VII, provided the best results tracking both absolute and relative changes in threshold versus the other nonparametric methods (peak of second and third time derivatives). The one parametric method evaluated, detection of threshold crossing of the first temporal derivative, performed comparably to these methods, provided that an appropriate threshold was chosen. We conclude that Methods II, VI, and VII were the best methods evaluated due to their performance across a wide range of action potential shapes and the fact that they are nonparametric. Our user database of responses may be useful to other investigators interested in developing additional methods in that it quantifies what has often been a subjective estimate.

Action Potentials↗

PubMed2003

Fundamentals of aggregation in concentrated dispersions: fiber-optic quasielastic light scattering and linear viscoelastic measurements.

Fiber-optic quasielastic light scattering and oscillatory shear rheology are employed to monitor the structure formation in concentrated, aqueous dispersions of model, electrostatically stabilized, polymer colloids. A regime of fractal scaling is observed in the vicinity or the gel point, as signified by a power law decay in the autocorrelation function with delay time and a power law dependence of the shear moduli on frequency. The power law exponents and the gel times extracted from the two techniques are compared for the first time on the same dispersion. The details of structure formation and aggregation kinetics in these concentrated dispersions are compared to the universal behavior of DLCA and RLCA aggregation observed at dilute concentrations in these and other dispersions, as well as to polymer gelation.

Journal Article↗

PubMed2003

Hybrid integrate-and-fire model of a bursting neuron.

We present a reduction of a Hodgkin-Huxley (HH)--style bursting model to a hybridized integrate-and-fire (IF) formalism based on a thorough bifurcation analysis of the neuron's dynamics. The model incorporates HH--style equations to evolve the subthreshold currents and includes IF mechanisms to characterize spike events and mediate interactions between the subthreshold and spiking currents. The hybrid IF model successfully reproduces the dynamic behavior and temporal characteristics of the full model over a wide range of activity, including bursting and tonic firing. Comparisons of timed computer simulations of the reduced model and the original model for both single neurons and moderately sized networks (n < or = 500) show that this model offers improvement in computational speed over the HH--style bursting model.

Action Potentials↗

PubMed2002

Periodicity, mixed-mode oscillations, and quasiperiodicity in a rhythm-generating neural network.

We studied patterns of oscillatory neural activity in the network that generates respiratory rhythm in mammals. When isolated in vitro, this network spontaneously generates an inspiratory-related motor rhythm, with stable amplitude from cycle to cycle. We show that progressively elevating neuronal excitability in vitro causes periodic modulation of this inspiratory rhythm, evoking (in order): mixed-mode oscillations, quasiperiodicity, and ultimately disorganized aperiodic activity. Thus, the respiratory network oscillator follows a well defined sequence of behavioral states characterized by dynamical systems theory, which includes discrete stages of periodic and quasiperiodic amplitude modulation and progresses (according to theory) to aperiodic chaos-like behavior. We also observed periodic, mixed-mode periodic, and quasiperiodic breathing patterns in neonatal rodents and human infants in vivo, suggesting that breathing patterns generated by the intact nervous system reflect deterministic neural activity patterns in the underlying rhythm-generating network.

Animals↗

PubMed2002

Persistent sodium current, membrane properties and bursting behavior of pre-bötzinger complex inspiratory neurons in vitro.

We measured persistent Na(+) current and membrane properties of bursting-pacemaker and nonbursting inspiratory neurons of the neonatal rat pre-Bötzinger complex (pre-BötC) in brain stem slice preparations with a rhythmically active respiratory network in vitro. In whole-cell recordings, slow voltage ramps (</=100 mV/s) inactivated the fast, spike-generating Na(+) current and yielded N-shaped current-voltage relationships with nonmonotonic, negative-slope regions between -60 and -35 mV when the voltage-sensitive component was isolated. The underlying current was a TTX-sensitive persistent Na(+) current (I(NaP)) since the inward current was present at slow voltage ramp speeds (3.3-100 mV/s) and the current was blocked by 1 microM TTX. We measured the biophysical properties of I(NaP) after subtracting the voltage-insensitive "leak" current (I(Leak)) in the presence of Cd(2+) and in some cases tetraethylammonium (TEA). Peak I(NaP) ranged from -50 to -200 pA at a membrane potential of -30 mV. Decreasing the speed of the voltage ramp caused time-dependent I(NaP) inactivation, but this current was present at ramp speeds as low as 3.3 mV/s. I(NaP) activated at -60 mV and obtained half-maximal activation near -40 mV. The subthreshold voltage dependence and slow inactivation kinetics of I(NaP), which closely resemble those of I(NaP) mathematically modeled as a burst-generation mechanism in pacemaker neurons of the pre-BötC, suggest that I(NaP) predominantly influences bursting dynamics of pre-BötC inspiratory pacemaker neurons in vitro. We also found that the ratio of persistent Na(+) conductance to leak conductance (g(NaP)/g(Leak)) can distinguish the phenotypic subpopulations of bursting pacemaker and nonbursting inspiratory neurons: pacemaker neurons showed g(NaP)/g(Leak) > g(NaP)/g(Leak) in nonpacemaker cells (P < 0.0002). We conclude that I(NaP) is ubiquitously expressed by pre-BötC inspiratory neurons and that bursting pacemaker behavior within the heterogeneous population of inspiratory neurons is achieved with specific ratios of these two conductances, g(NaP) and g(Leak).

Animals↗

PubMedDate not supplied

A new strategy for the preparation of supramolecular neutral hydrogels.

This paper demonstrates that miscible blends from water-insoluble polymers, such as poly(2,4,4-trimethylhexamethylene terephthalamide) (1), methylamine imidized poly(methyl methacrylate) (2), and aromatic poly(ether sulfone) (3) and water-soluble polymers, such as poly(2-ethyl-2-oxazoline) (4) and poly(N-vinyl pyrrolidone) (5), respectively, represent a new class of supramolecular hydrogels. When the degree of polymerization (DP) of the water-soluble polymer is larger than that of water-insoluble polymer, the resulting hydrogels adsorb extremely high amounts of water (i.e., 229 wt % in the case of the hydrogel 1/4) and remain mechanically tough. The high water uptake capability of these blends is explained by a supramolecular network structure generated by H-bonding and/or other noncovalent interactions between the water-insoluble hydrophobic polymer and water-soluble hydrophilic segments as reversible cross-linking points interconnected by hydrophilic water soluble segments. The glass transition temperatures of these hydrogels are tailored via the ratio between the weight percent of the two polymers and by the glass transition temperature of the parent polymers. These supramolecular hydrogels can be processed from melt or solution and maintain excellent mechanical properties both in dry and in the water swollen state. This class of hydrogels is of interest for areas such as membranes, contact lenses, tissue engineering, and other biomedical applications.

Adsorption↗