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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modifications based on experimental results reported in the literature are made to the Hodgkin-Huxley equations to describe the electrophysiological behavior of the Aplysia abdominal ganglion R15 cell. The system is then further modified to describe the effects with the application of the drug tetrodotoxin (TTX) to the cells' bathing medium. Methods of the qualitative theory of differential equations are used to determine the conditions necessary for such a system of equations to have an oscillatory solution. A model satisfying these conditions is shown to preduct many experimental observations of R15 cell behavior. Numerical solutions are obtained for differential equations satisfying the conditions of the model. These solutions are shown to have a form similar to that of the bursting which is characteristic of this cell, and to preduct many results of experiments conducted on this cell. The physiological implications of the model are discussed.
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PMID:Mathematical description of a bursting pacemaker neuron by a modification of the Hodgkin-Huxley equations. 125 78

Larger axons usually have faster conduction velocities, lower thresholds, and larger extracellular action potentials than smaller axons. However, it has been shown that the largest fiber, R2, in the right pleurovisceral connective of the marine mollusc, Aplysia, has a higher threshold and a slower conduction velocity than does the smaller axon of cell RI, even though the amplitude of R2's spike is larger than R1's spike. One explanation of this apparent parodox is that the two axons have different "intrinsic membrane and axoplasmic constants" (Goldman, L. (1961), J. Cell Comp. Physiol. 57: 185-191). However, the deep infolding of R2's axonal membrane suggested that differences in the shape of the two axons might also account for the paradox. Accordingly, we measured the conduction velocities of the two axons and then examined the same axons in the electron microscope in order to measure their volumes and surface areas. Our morphological observations indicate that the extensive infolding of surface membrane causes R2 to have a smaller volume to surface area ratio than R1. Thus, since conduction velocity is proportional to the square root of the volume to surface area ratio (Hodgkin, A.L. (1954), J. Physiol. 125: 221-224), it is predictable that the smaller axon would have a faster conduction velocity. The results suggest that the paradoxical conduction velocities can be explained largely as resulting from differences in the shapes of the two axons. However, certain discrepancies between the measured and the predicted values suggest that other factors are contributing as well.
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PMID:Anatomical basis for an apparent paradox concerning conduction velocities of two identified axons in Aplysia. 127 Oct 55

Action potentials, macroscopic ionic currents and single channel currents were recorded from growth cones of Aplysia right upper quadrant (r.u.q.) cells in culture, using the patch-clamp technique. Recordings were obtained from both intact growth cones and from growth cones that had been mechanically isolated from the rest of the neurone. In current-clamp mode, greater than half of the isolated growth cones display an all-or-none action potential when depolarized above 0 mV with outward current pulses. The remaining growth cones display only a graded depolarization that is unaffected by tetrodotoxin (TTX). In whole-cell voltage clamp almost all isolated growth cones display a rapidly activating and inactivating inward current followed by a delayed outward current in response to depolarizations positive to -20 mV. The rapid inward current reverses direction at around +70 to +80 mV and is completely suppressed by 100 microM-TTX, which suggests that this current is carried by the fast Hodgkin-Huxley sodium current channels. The delayed outward current appears to result from the activation of both the delayed rectifier potassium current, IK, and the calcium-activated potassium current, IC. The growth cones do not display any prominent early transient outward current, IA. The sodium current, INA, was studied in isolation by substituting caesium for potassium ions in the pipette solution. INa is half-inactivated at a holding potential of -36 mV, reaches half-maximal activation with a depolarization to 0 mV, and has a mean peak current density of 13 microA/cm2. The time course of inactivation is well described by a single exponential (tau = 3 ms at 0 mV). In cell-attached patches, a rapidly activating and inactivating inward current channel was recorded with an average unit conductance of 6.9 pS. The activation and inactivation parameters of the ensemble averaged current closely match the measured values from the macroscopic sodium current. At very positive potentials we recorded a voltage-dependent outward current channel with a conductance of around 35 pS. No significant inward calcium current was observed in whole-cell measurements and few single calcium channel currents were measured in cell-attached patches, suggesting a sparse distribution of calcium channels in the r.u.q. growth cones.
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PMID:Action potentials, macroscopic and single channel currents recorded from growth cones of Aplysia neurones in culture. 242 3

Conduction in inward rectifier, K+-channels in Aplysia neuron and Ba++ blockade of these channels were studied by rapid measurement of the membrane complex admittance in the frequency range 0.05 to 200 Hz during voltage clamps to membrane potentials in the range -90 to -40 mV. Complex ionic conductances of K+ and Cl- rectifiers were extracted from complex admittances of other membrane conduction processes and capacitance by vector subtraction of the membrane complex admittance during suppressed inward K+ current (near zero-mean current and in zero [K+]0) from complex admittances determined at other [K+]0 and membrane potentials. The contribution of the K+ rectifier to the admittance is distinguishable in the frequency domain above 1 Hz from the contribution of the Cl- rectifier, which is only apparent at frequencies less than 0.1 Hz. The voltage dependence (-90 to -40 mV) of the chord conductance (0.2 to 0.05 microS) and the relaxation time (4-8 ms) of K+ rectifier channels at [K+]0 = 40 mM were determined by curve fits of admittance data by a membrane admittance model based on the linearized Hodgkin-Huxley equations. The conductance of inward rectifier, K+ channels at a membrane potential of -80 mV had a square-root dependence on external K+ concentration, and the relaxation time increased from 2 to 7.5 ms for [K+]0 = 20 and 100 mM, respectively. The complex conductance of the inward K+ rectifier, affected by Ba++, was obtained by complex vector subtraction of the membrane admittance during blockage of inward rectifier, K+ channels (at -35 mV and [Ba++]0 = 5 mM) from admittances determined at -80 mV and at other Ba++ concentrations. The relaxation time of the blockade process decreased with increases in Ba++ concentration. An open-closed channel state model produces the inductive-like kinetic behavior in the complex conductance of inward rectifier, K+ channels and the addition of a blocked channel state accounts for the capacitive-like kinetic behavior of the Ba++ blockade process.
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PMID:Inward rectifier K+-channel kinetics from analysis of the complex conductance of Aplysia neuronal membrane. 245 51

1. We describe a simulator for neural networks and action potentials (SNNAP) that can simulate up to 30 neurons, each with up to 30 voltage-dependent conductances, 30 electrical synapses, and 30 multicomponent chemical synapses. Voltage-dependent conductances are described by Hodgkin-Huxley type equations, and the contributions of time-dependent synaptic conductances are described by second-order differential equations. The program also incorporates equations for simulating different types of neural modulation and synaptic plasticity. 2. Parameters, initial conditions, and output options for SNNAP are passed to the program through a number of modular ASCII files. These modules can be modified by commonly available text editors that use a conventional (i.e., character based) interface or by an editor incorporated into SNNAP that uses a graphical interface. The modular design facilitates the incorporation of existing modules into new simulations. Thus libraries can be developed of files describing distinctive cell types and files describing distinctive neural networks. 3. Several different types of neurons with distinct biophysical properties and firing properties were simulated by incorporating different combinations of voltage-dependent Na+, Ca2+, and K+ channels as well as Ca(2+)-activated and Ca(2+)-inactivated channels. Simulated cells included those that respond to depolarization with tonic firing, adaptive firing, or plateau potentials as well as endogenous pacemaker and bursting cells. 4. Several types of simple neural networks were simulated that included feed-forward excitatory and inhibitory chemical synaptic connections, a network of electrically coupled cells, and a network with feedback chemical synaptic connections that simulated rhythmic neural activity. In addition, with the use of the equations describing electrical coupling, current flow in a branched neuron with 18 compartments was simulated. 5. Enhancement of excitability and enhancement of transmitter release, produced by modulatory transmitters, were simulated by second-messenger-induced modulation of K+ currents. A depletion model for synaptic depression was also simulated. 6. We also attempted to simulate the features of a more complicated central pattern generator, inspired by the properties of neurons in the buccal ganglia of Aplysia. Dynamic changes in the activity of this central pattern generator were produced by a second-messenger-induced modulation of a slow inward current in one of the neurons.
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PMID:Simulator for neural networks and action potentials: description and application. 751 28

Potassium currents in pleural sensory neurons of Aplysia were studied under control conditions and in the presence of serotonin (5-HT). Using pharmacological techniques we isolated a current that we refer to as IK,V. Although it is not known whether IK,V represents a distinct type of membrane channel, we described its properties using a Hodgkin-Huxley type model. The effects of 5-HT on IK,V were complex. 5-HT decreased by 50% the steady-state magnitude (Iss) of IK,V in response to a voltage-clamp pulse from -50 mV to +20 mV. In addition, 5-HT significantly slowed both activation kinetics (the time constant of activation was increased by 29% at +20 mV) and inactivation kinetics (the time constant of inactivation was increased by 518% at +20 mV). Mathematical descriptions of IK,V in control conditions and in the presence of 5-HT were used to estimate the relative contribution of serotonergic modulation of IK,V to the total 5-HT-induced modulation of membrane currents. Effects of 5-HT on IK,V account for more than 87% of the 5-HT-induced reduction in outward current during the first 20 ms of a voltage-clamp pulse to +20 mV. This result implies that 5-HT exerts many of its effects on spike width in sensory neurons via modulation of IK,V. Effects of 5-HT on IK,V are consistent with a model in which the maximal conductance underlying the current is decreased by 50%, and the rate constants between open and closed states of both the activation and inactivation processes are diminished in magnitude across all membrane potentials.
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PMID:Analysis of the modulation by serotonin of a voltage-dependent potassium current in sensory neurons of Aplysia. 801 2

Serotonergic modulation of the sensory neurons that mediate the gill- and tail-withdrawal reflexes of Aplysia is a useful model system for studies of neuronal plasticity that contributes to learning and memory. The effects of serotonin (5-HT) are mediated, in part, via two protein kinases (protein kinase A, PKA, and protein kinase C, PKC), which in turn, modulate at least four membrane currents, including a S ("serotonin-sensitive") K(+) current (I(K, S)), a steeply voltage-dependent K(+) current (I(K-V)), a slow component of the Ca(2+)-activated K(+) current (I(K,Ca-S)), and a L-type Ca(2+) current (I(Ca-L)). The present study investigated how the modulation of these currents altered the spike duration and excitability of sensory neurons and examined the relative contributions of PKA- and PKC-mediated effects to the actions of 5-HT. A Hodgkin-Huxley type model was developed that described the ionic conductances in the somata of sensory neurons. The descriptions of these currents and their modulation were based largely on voltage-clamp data from sensory neurons. Simulations were preformed with the program SNNAP (Simulator for Neural Networks and Action Potentials). The model was sufficient to replicate empirical data that describes the membrane currents, action potential waveform and excitability as well as their modulation by application of 5-HT, increased levels of adenosine cyclic monophosphate or application of active phorbol esters. In the model, modulation of I(K-V) by PKC played a dominate role in 5-HT-induced spike broadening, whereas the concurrent modulation of I(K,S) and I(K,Ca-S) by PKA primarily accounted for 5-HT-induced increases in excitability. Finally, simulations indicated that a PKC-induced increase in excitability resulted from decreases of I(K,S) and I(K,Ca-S), which was likely the indirect result of cross-talk between the PKC and PKA systems. The results provide several predictions that warrant additional experimental investigation and illustrate the importance of considering indirect as well as direct effects of modulatory agents on the modulation of membrane currents.
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PMID:Computational model of the serotonergic modulation of sensory neurons in Aplysia. 1060 29

Synchronization of neural activity is fundamental for many functions of the brain. We demonstrate that spike-timing dependent plasticity (STDP) enhances synchronization (entrainment) in a hybrid circuit composed of a spike generator, a dynamic clamp emulating an excitatory plastic synapse, and a chemically isolated neuron from the Aplysia abdominal ganglion. Fixed-phase entrainment of the Aplysia neuron to the spike generator is possible for a much wider range of frequency ratios and is more precise and more robust with the plastic synapse than with a nonplastic synapse of comparable strength. Further analysis in a computational model of Hodgkin-Huxley-type neurons reveals the mechanism behind this significant enhancement in synchronization. The experimentally observed STDP plasticity curve appears to be designed to adjust synaptic strength to a value suitable for stable entrainment of the postsynaptic neuron. One functional role of STDP might therefore be to facilitate synchronization or entrainment of nonidentical neurons.
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PMID:Enhancement of synchronization in a hybrid neural circuit by spike-timing dependent plasticity. 1458 5

The potential neurophysiological applications of high frequency AC stimulation (HFAC) in blocking conduction has led to a series of experimental and modeling studies analyzing the effect of HFAC conduction block on mixed nerves. However, many of these computational studies have been based on axon models that are perhaps not valid for the nerves under study. The isolated response of unmyelinated nerves to HFAC has also not been previously studied. In this study, 5-50 kHz sinusoidal HFAC stimulation waveforms were used to reversibly block conduction through the unmyelinated nerve fibers of Aplysia. Unlike myelinated nerves, the minimum HFAC amplitude for blocking conduction in these nerves showed a non-monotonic behavior with frequency. The Hodgkin-Huxley model did not accurately predict the experimentally observed trends but modifying the model to incorporate a frequency-dependent membrane capacitance resulted in a significant change in the high frequency response of the model while still preserving the standard characteristics of action potential propagation.
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PMID:Conduction block induced by high frequency AC stimulation in unmyelinated nerves. 1800 7

Biophysical properties of neurons contributing to the ability of an animal to decide whether or not to respond were examined. B31/B32, two pairs of bilaterally symmetrical Aplysia neurons, are major participants in deciding to initiate a buccal motor program, the neural correlate of a consummatory feeding response. B31/B32 respond to an adequate stimulus after a delay, during which time additional stimuli influence the decision to respond. B31/B32 then respond with a ramp depolarization followed by a sustained soma depolarization and axon spiking that is the expression of a commitment to respond to food. Four currents contributing to decision making in B31/B32 were characterized, and their functional effects were determined, in current- and voltage-clamp experiments and with simulations. Inward currents arising from slow muscarinic transmission were characterized. These currents contribute to the B31/B32 depolarization. Their slow activation kinetics contribute to the delay preceding B31/B32 activity. After the delay, inward currents affect B31/B32 in the context of two endogenous inactivating outward currents: a delayed rectifier K+ current (I(K-V)) and an A-type K+ current (I(K-A)), as well as a high-threshold noninactivating outward current (I(maintained)). Hodgkin-Huxley kinetic analyses were performed on the outward currents. Simulations using equations from these analyses showed that I(K-V) and I(K-A) slow the ramp depolarization preceding the sustained depolarization. The three outward currents contribute to braking the B31/B32 depolarization and keeping the sustained depolarization at a constant voltage. The currents identified are sufficient to explain the properties of B31/B32 that play a role in generating the decision to feed.
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PMID:Currents contributing to decision making in neurons B31/B32 of Aplysia. 1803 63


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