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Biomedical subjects

E Marder

Publications and source records attributed to E Marder.

At least 73 records · Page 4Linked to original sources
PubMed1995

Selective regulation of current densities underlies spontaneous changes in the activity of cultured neurons.

We study the electrical activity patterns and the expression of conductances in adult stomatogastric ganglion (STG) neurons as a function of time in primary cell culture. When first plated in culture, these neurons had few active properties. After 1 d in culture they produced small action potentials that rapidly inactivated during maintained depolarization. After 2 d in culture they fired large action potentials tonically when depolarized, and their properties resembled very closely the properties of STG neurons pharmacologically isolated in the ganglion. After 3-4 d in culture, however, their electrical properties changed and they fired in bursts when depolarized. We characterized the currents expressed by these neurons in culture. They included two TTX-sensitive sodium currents, a calcium current, a delayed-rectifier-like current, a calcium-dependent potassium current, and two A-type currents. The changes in firing properties with time in culture were accompanied by an increase in inward and decrease in outward current densities. A single-compartment conductance-based model of an STG neuron was constructed by fitting the currents measured in the biological neurons. When the current densities in the model neuron were matched to those measured for the biological neurons in each activity state, the model neuron closely reproduced each state, indicating that the changes in current densities are sufficient to account for the changes in intrinsic properties. These data indicate that STG neurons isolated in culture change their intrinsic electrical properties by selectively adjusting the magnitudes of their ionic conductances.

Animals↗
PubMed1994

Activity-dependent current distributions in model neurons.

The electrical activity of a neuron can affect its intrinsic physiological characteristics through a wide range of processes. We study a computer-simulated multicompartment model neuron in which channel density depends on local Ca2+ concentrations. This has three interesting consequences for the spatial distribution of conductances and the physiological behavior of the neuron: (i) the model neuron spontaneously develops a realistic, nonuniform distribution of conductances that is linked both to the morphology of the neuron and to the pattern of synaptic input that it receives, (ii) the response to synaptic input reveals a form of intrinsic localized plasticity that balances the synaptic contribution from dendritic regions receiving unequal stimulation, and (iii) intrinsic plasticity establishes a biophysical gain control that restores the neuron to its optimal firing range after synapses are strengthened by "Hebbian" long-term potentiation.

Calcium↗
PubMed1994

Switching neurons are integral members of multiple oscillatory networks.

BACKGROUND: The stomatogastric ganglion of the crab Cancer borealis contains the neurons that generate several different behaviors, such as the fast pyloric rhythm and the slower gastric-mill rhythm. It has previously been shown that many stomatogastric ganglion neurons can switch between pyloric- and gastric-timed activity. However, the question remained whether these neurons really are integral members of several central-pattern-generating networks, or just passive followers that only change their activity patterns in response to a switch determined by other neurons. RESULTS: To address this question, we perturbed the activity of the 'pyloric' ventricular dilator neuron and the 'gastric' lateral gastric neuron during ongoing pyloric and gastric rhythms. In the absence of ongoing gastric rhythms, these neurons can fire in pyloric time, and perturbing them can reset the pyloric rhythm. During robust gastric activity, the lateral gastric and ventricular dilator neurons can fire in gastric time, and perturbing them can reset the gastric rhythm. CONCLUSIONS: When stomatogastric ganglion neurons change their firing patterns, they also function as part of the circuitry that generates the new rhythm with which they are firing, demonstrating that individual neurons can be used as part of multiple pattern-generating circuits.

Animals↗
PubMed1994

Activity-dependent changes in the intrinsic properties of cultured neurons.

Learning and memory arise through activity-dependent modifications of neural circuits. Although the activity dependence of synaptic efficacy has been studied extensively, less is known about how activity shapes the intrinsic electrical properties of neurons. Lobster stomatogastric ganglion neurons fire in bursts when receiving synaptic and modulatory input but fire tonically when pharmacologically isolated. Long-term isolation in culture changed their intrinsic activity from tonic firing to burst firing. Rhythmic stimulation reversed this transition through a mechanism that was mediated by a rise in intracellular calcium concentration. These data suggest that neurons regulate their conductances to maintain stable activity patterns and that the intrinsic properties of a neuron depend on its recent history of activation.

Animals↗
PubMed1994

Mechanisms for oscillation and frequency control in reciprocally inhibitory model neural networks.

We describe four different mechanisms that lead to oscillations in a network of two reciprocally inhibitory cells. In two cases (intrinsic release and intrinsic escape) the frequency of the network oscillation is insensitive to the threshold voltage of the synaptic potentials. In the other two cases (synaptic release and synaptic escape) the network frequency is strongly determined by the threshold voltage of the synaptic connections. The distinction between the different mechanisms blurs as the function describing synaptic activation becomes less steep and as the model neurons are removed from the relaxation regime. These mechanisms provide insight into the parameters that control network frequency in motor systems that depend on reciprocal inhibition.

Animals↗
PubMed1993

Activity-dependent regulation of conductances in model neurons.

Neurons maintain their electrical activity patterns despite channel turnover, cell growth, and variable extracellular conditions. A model is presented in which maximal conductances of ionic currents depend on the intracellular concentration of calcium ions and so, indirectly, on activity. Model neurons with activity-dependent maximal conductances modify their conductances to maintain a given behavior when perturbed. Moreover, neurons that are described by identical sets of equations can develop different properties in response to different patterns of presynaptic activity.

Animals↗
PubMed1993

Spike initiation and propagation on axons with slow inward currents.

We investigate spike initiation and propagation in a model axon that has a slow regenerative conductance as well as the usual Hodgkin-Huxley type sodium and potassium conductances. We study the role of slow conductance in producing repetitive firing, compute the dispersion relation for an axon with an additional slow conductance, and show that under appropriate conditions such an axon can produce a traveling zone of secondary spike initiation. This study illustrates some of the complex dynamics shown by excitable membranes with fast and slow conductances.

Action Potentials↗
PubMed1993

The dynamic clamp: artificial conductances in biological neurons.

The dynamic clamp is a novel method that uses computer simulation to introduce conductances into biological neurons. This method can be used to study the role of various conductances in shaping the activity of single neurons, or neurons within networks. The dynamic clamp can also be used to form circuits from previously unconnected neurons. This approach makes computer simulation an interactive experimental tool, and will be useful in many applications where the role of synaptic strengths and intrinsic properties in neuronal and network dynamics is of interest.

Animals↗
PubMed1993

Dynamic clamp: computer-generated conductances in real neurons.

1. We describe a new method, the dynamic clamp, that uses a computer as an interactive tool to introduce simulated voltage and ligand mediated conductances into real neurons. 2. We simulate a gamma-aminobutyric acid (GABA) response of a cultured stomatogastric ganglion neuron to illustrate that the dynamic clamp effectively introduces a conductance into the target neuron. 3. To demonstrate an artificial voltage-dependent conductance, we simulate the action of a voltage-dependent proctolin response on a neuron in the intact stomatogastric ganglion. We show that shifts in the activation curve and the maximal conductance of the response produce different effects on the target neuron. 4. The dynamic clamp is used to construct reciprocal inhibitory synapses between two stomatogastric ganglion neurons that are not coupled naturally, illustrating that this method can be used to form new networks at will.

Animals↗
PubMed1993

Modulation of identified stomatogastric ganglion neurons in primary cell culture.

1. We studied the properties of identified stomatogastric ganglion (STG) neurons grown in complete isolation in primary cell culture. 2. STG neurons isolated with a short piece of primary neurite adhered to the culture dishes and extended neurites. Outgrowth was apparent within several hours, and continued for < or = 5 days. 3. After 1 day in culture, most STG neurons were not capable of producing action potentials or oscillations. After 3-5 days in culture, most STG neurons regained the ability to fire action potentials, and some became endogenous bursters. Neurons in culture 3-5 days possessed many of the physiological properties of STG neurons in situ, including postinhibitory rebound, a hyperpolarization-activated depolarizing voltage sag, and the ability to burst in the presence of the potassium channel blocker tetraethyl-ammonium. 4. Identified cultured neurons responded appropriately to a variety of neuromodulators, including the monoamines dopamine and octopamine, the muscarinic agonist pilocarpine, and the peptide proctolin. These data suggest that the maintenance of receptor expression in fully differentiated STG neurons is not affected by isolation from all synaptic and modulatory influences. 5. In contrast to the other modulators tested, the effects of serotonin on cultured neurons differed from those reported in situ. Two cell types that are reported to be hyperpolarized by serotonin in situ, the lateral pyloric and pyloric neurons, were depolarized by serotonin in culture.

Action Potentials↗
PubMed1993

The effects of SDRNFLRFamide and TNRNFLRFamide on the motor patterns of the stomatogastric ganglion of the crab Cancer borealis.

TNRNFLRFamide was isolated and sequenced from the stomatogastric nervous system of the crab Cancer borealis by reverse-phase high performance liquid chromatography followed by automated Edman degradation. An SDRNFLRFamide-like peptide that exactly co-migrated with SDRNFLRFamide was also observed. The effects of TNRNFLRFamide and SDRNFLRFamide on the gastric and pyloric rhythms of the stomatogastric nervous system of the crab Cancer borealis were studied. Both peptides activated pyloric rhythms in quiescent preparations in a dose-dependent manner with a threshold between 10(-11) and 10(-10) mol l-1. Both peptides increased the pyloric rhythm frequency of preparations showing moderate activity levels and had relatively little effect on preparations that showed strong pyloric rhythms prior to peptide application. Both peptides evoked gastric mill activity in preparations without existing gastric rhythms. The activation of the gastric rhythm is associated with activation of oscillatory properties in the dorsal gastric neurone. The induction of gastric rhythms by these peptides was accompanied by switches from pyloric-timed activity to gastric-timed activity by several stomatogastric ganglion neurones. Application of these peptides provides direct experimental control of circuit modification in the stomatogastric nervous system.

Amino Acid Sequence↗
PubMed1993

Frequency and burst duration in oscillating neurons and two-cell networks.

We study the relationship of injected current to oscillator period in single neurons and two-cell model networks formed by reciprocal inhibitory synapses. Using a Morris-Lecar-like model, we identify two qualitative types of oscillatory behavior for single model neurons. The "classical" oscillator behavior is defined as type A. Here the burst duration is relatively constant and the frequency increases with depolarization. For oscillator type B, the frequency first increases and then decreases when depolarized, due to the variable burst duration. Our simulations show that relatively modest changes in the maximal inward and outward conductances can move the oscillator from one type to another. Cultured stomatogastric ganglion neurons exhibit both A and B type behaviors and can switch between the two types with pharmacological manipulation. Our simulations indicate that the stability of a two-cell network with injected current can be extended with inhibitory coupling. In addition, two-cell networks formed from type A or type B oscillators behave differently from each other at lower synaptic strengths.

Animals↗
PubMed1993

The behavioral repertoire of the gastric mill in the crab, Cancer pagurus: an in situ endoscopic and electrophysiological examination.

Simultaneous endoscopic and electrophysiological recordings were used to observe the behavior of the gastric mill complex while recording the motor output of the stomatogastric ganglion (STG) in intact crabs. In the crab STG, many pattern-generating neurons are able to fire in several distinct rhythmic motor patterns. Specifically, many neurons can switch between firing in time with the rapid pyloric rhythm to firing in time with the slower gastric mill rhythm (Weimann et al., 1991). We now correlate behaviorally relevant movements of the gastric mill with some of the modifications of neuronal firing patterns previously characterized using in vitro STG preparations. The intracellular and extracellular recordings from the intact crab are largely indistinguishable from those obtained from in vitro preparations. For the first time, we describe the movements that result as neurons switch their activity patterns associated with activation of the gastric mill rhythm. Extracellular stimulation and intracellular depolarization of individual motor neurons is used to determine the relationship between frequency of firing and movement in behaving animals.

Animals↗
PubMed1992

Reduction of conductance-based neuron models.

We present a scheme for systematically reducing the number of differential equations required for biophysically realistic neuron models. The techniques are general, are designed to be applicable to a large set of such models and retain in the reduced system as high a degree of fidelity to the original system as possible. As examples, we provide reductions of the Hodgkin-Huxley system and the A-current model of Connor et al. (1977).

Mathematics↗
PubMed1992

Ionic currents of the lateral pyloric neuron of the stomatogastric ganglion of the crab.

1. The lateral pyloric (LP) neuron is an important component of the network that generates the pyloric rhythm of the stomatogastric ganglion (STG) and is a direct target of many modulatory inputs to the STG. Our aim in this and the subsequent two papers is to describe the conductances present in this cell and to understand the role these conductances play in shaping the activity of the neuron. 2. LP neurons were studied in two-electrode voltage clamp (TEVC) in a saline solution containing tetrodotoxin (TTX) and picrotoxin (PTX) to isolate them pharmacologically from presynaptic inputs. 3. We identified six voltage-dependent ionic conductances. These include three outward currents that resemble a delayed rectifier current, a Ca(2+)-activated K+ current and an A-current similar to those seen in many other preparations. LP neurons show three inward currents, a fast TTX-sensitive current, a hyperpolarization-activated inward current, and a Ca2+ current.

4-Aminopyridine↗
PubMed1992

Mathematical model of an identified stomatogastric ganglion neuron.

1. The ionic currents in the lateral pyloric (LP) cell of the stomatogastric ganglion (STG) described in the preceding paper of the rock crab Cancer borealis were fit with a set of differential equations that describe their voltage, time, and Ca2+ dependence. The voltage-dependent currents modeled are a delayed rectifier-like current, id; a Ca(2+)-activated outward current, io(Ca); a transient A-like current, iA; a Ca2+ current, iCa; an inwardly rectifying current, ih; and a fast tetrodotoxin (TTX)-sensitive Na+ current, iNa. 2. A single-compartment, isopotential model of the LP cell was constructed from the six voltage-dependent currents, a voltage-independent leak current il, a Ca2+ buffering system, and the membrane capacitance. 3. The behavior of the model LP neuron was compared with that of the biological neuron by simulating physiological experiments carried out in both voltage-clamp and current-clamp modes. The model and biological neurons show similar action-potential shapes, durations, steady-state current-voltage (I-V) curves, and respond to injected current in a comparable way.

Action Potentials↗