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R D Traub

Publications and source records attributed to R D Traub.

At least 91 records · Page 5Linked to original sources
PubMed1987

Models of synchronized hippocampal bursts in the presence of inhibition. I. Single population events.

1. We constructed model networks with 520 or 1,020 cells intended to represent the CA3 region of the hippocampus. Model neurons were simulated in enough detail to reproduce intrinsic bursting and the electrotonic flow of currents along dendritic cables. Neurons exerted either excitatory or inhibitory postsynaptic actions on other cells. The network models were simulated with different levels of excitatory and inhibitory synaptic strengths in order to study epileptic and other interesting collective behaviors in the system. 2. Excitatory synapses between neurons in the network were powerful enough so that burst firing in a presynaptic neuron would evoke bursting in its connected cells. Since orthodromic or antidromic stimulation evokes both a fast and a slow phase of inhibition, two types of inhibitory cells were simulated. The properties of these inhibitory cells were modeled to resemble those of two types of inhibitory cells characterized by dual intracellular recordings in the slice preparation. 3. With fast inhibition totally blocked, a stimulus to a single cell lead to a synchronized population burst. Thus the principles of our epileptic synchronization model, developed earlier, apply even when slow inhibitory postsynaptic potentials (IPSPs) are present, as apparently occurs in the epileptic hippocampal slice. The model performs in this way because bursting can propagate through several generations in the network before slow inhibition builds up enough to block burst propagation. This can occur, however, only if connectivity is sufficiently large. With very low connection densities, slow IPSPs will prevent the development of full synchronization. 4. We performed multiple simulations in which the fast inhibitory conductance strength was kept fixed at various levels while the strength of the excitatory synapses was varied. In each simulation, we stimulated either one or four cells. For each level of inhibition, the peak number of cells bursting depended sensitively on excitatory synaptic strength, showing a sudden increase as this strength reached a critical level. The critical excitation, which depended on the level of inhibition, corresponded to the level at which bursting can propagate from cell to cell at the particular level of inhibition. 5. We performed an analogous series of simulations in which the strength of excitatory synapses was held constant while the strength of fast inhibitory synapses was varied, stimulating a single neuron in each case. These simulations correspond to experiments that have been done in the hippocampal slice as low doses of picrotoxin are washed into a slice, gradually abolishing fast inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Models of synchronized hippocampal bursts in the presence of inhibition. II. Ongoing spontaneous population events.

1. We extended our computer model of the CA3 region of the hippocampal slice in order to study spontaneous activity occurring in the presence and absence of synaptic inhibition. This was done by providing a steady inward current to the excitatory neurons, whose value was randomly chosen for each cell. With the parameters used, many of the excitatory cells would, if synaptically isolated, remain quiescent, whereas others would burst periodically with periods as brief as 750 ms. Simulations were run for as long as 10 s of neural activity. 2. In the presence of synaptic inhibition, neural activity became organized into recurring, partially synchronized events: clusters of neurons (6% to 12% of the population) would discharge together, with a period averaging 340 ms, shorter than the burst period of any individual neuron. A consequence of periodic clusters of cellular bursts was the widespread occurrence of periodic synchronized synaptic potentials, as have been observed in hippocampal slices and human temporal neocortical slices. The periods between these synaptic potentials are similar in the model to those observed experimentally. 3. The period could be slowed by either increasing the time constant of the slow inhibitory postsynaptic potential (IPSP), or by making the excitatory synapses more powerful. The period seems to be generated in part as follows. Consider those cells with rapid spontaneous discharge rates. An upper bound for the period corresponds to the interval between 1) such a cell's becoming responsive enough to an excitatory synaptic input to burst, and 2) such a cell's bursting spontaneously (i.e., in response to its own intrinsic inward current). For cells with rapid spontaneous discharge rates, the interval defined in this way is approximately 350 ms. 4. Different cells participated in each cluster. A given cluster was initiated by one cell or by two cells bursting together, and spread via excitatory synapses. Excitatory synaptic paths could be traced from the initiating cell(s), directly or through other participants, to all cells participating in a cluster. Spread of activity was limited by two mechanisms, so that not all cells synaptically excited by a participating cell would themselves participate. First, cells might be refractory from having participated in a recent cluster (since the intercluster period was less than the refractory time from a cellular burst to its responsiveness to a synaptic stimulus). Second, some cells might be synaptically inhibited. Synaptic inhibition in this model did not act rapidly enough to suppress the cluster totally.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Cellular basis of neuronal synchrony in epilepsy.

Synchronized discharge of populations of cortical neurons are often observed to underly both the interictal spikes and tonic seizures generated in experimental epilepsy studies. Recently it has been shown that similar synchronized discharges occur in cortical brain slices treated with convulsants such as penicillin, picrotoxin, or bicuculline. The favorable experimental conditions offered by the in vitro preparation have facilitated a detailed examination on the cellular basis for the generation of the epileptic neuronal synchrony. In this chapter we shall review some experimental observations on the neuronal synchronization and describe a mechanism for its generation based on the computer simulation approach. Three factors are considered to be essential for epileptic synchronization observation in vitro. First, cortical neurons may intrinsically generate bursts of action potentials. Second, recurrent excitatory connections exist that are sufficiently powerful that bursting activity may spread between synaptically connected neurons. Third, inhibition within the local neuronal circuit must be adequately attenuated to allow excitation to spread through the recurrent excitatory connections. Computer simulation studies have been based on these assumptions, using neuronal networks where each cell is connected to more than one postsynaptic neuron. Bursting initiated in one cell excites all its follower cells, and the sequential recruitment of an increasing number of cells eventually leads to a simultaneous discharge of the population. A number of recent experimental observations lend credence to the proposed scheme for neuronal synchrony. Simultaneous paired intracellular recordings provided direct evidence that a burst of action potentials in a presynaptic cell can activate action potentials postsynaptically. Furthermore, it is shown that the rhythm of spontaneous discharge in a neuronal population can be influenced by the activity of one neuron within the population.

Animals↗
PubMed1985

Computer simulations indicate that electrical field effects contribute to the shape of the epileptiform field potential.

In the presence of convulsant drugs such as picrotoxin, neurons in the hippocampal-slice preparation generate synchronized depolarizing bursts. This synchrony occurs on a time scale of tens of milliseconds and is produced by excitatory synaptic interactions between neurons. The synaptic interactions themselves occur on a time scale of tens of milliseconds. The "epileptiform" local-field potential during such synchronized bursts is comb-shaped ("ringing"), whereas the field potential expected if action potentials in neighboring neurons were uncorrelated is noisy and not comb-shaped. This suggests that individual action potentials are locally synchronized on a time scale of 1 ms. We have previously shown, using computer simulations, that electrical interactions--mediated by currents flowing in the extracellular medium--can plausibly explain action-potential synchronization in experiments where chemical synapses are blocked. The present simulations demonstrate that electrical interactions can also account for action-potential synchronization--and thus the "ringing" shape of the field potential--during epileptiform bursts, where excitatory synapses are functional. The field potential is thus a modulating influence on, as well as a reflection of, underlying neuronal transmembrane events.

Action Potentials↗
PubMed1985

Simulation of hippocampal afterdischarges synchronized by electrical interactions.

Recent experiments have shown that hippocampal pyramidal cells can generate synchronized action potentials even when chemical synapses are blocked. The computer simulations reported here showed that communication between cells by extracellular currents could cause this synchrony, provided that (1) individual neurons were sufficiently excitable and that (2) the resistivity of the extracellular medium was sufficiently high. Synchronization was enhanced if electronic junctions were also present.

Action Potentials↗
PubMed1985

Neuronal interactions during epileptic events in vitro.

Epileptic events can be produced in in vitro brain slices after perfusion with convulsant agents such as penicillin or picrotoxin. These events consist of one or more synchronized neuronal bursts. In this experimental system, epileptic events occur because of blockade of synaptic inhibition by the convulsant agent. A sparse network of excitatory synaptic interconnections in the hippocampus serves to synchronize a population of neurons, each of which is capable of bursting after appropriate stimulation.

Action Potentials↗
PubMed1984

Synchronized afterdischarges in the hippocampus: contribution of local synaptic interactions.

In the presence of picrotoxin, spontaneous synchronized bursts followed by afterdischarges were recorded from all pyramidal cell regions of the guinea pig hippocampal slice. Excitatory synaptic potentials, which reversed at approx -5 mV, were found to be associated with both the initial burst and each afterdischarge. Afterdischarges were reversibly blocked, leaving the initial synchronized burst intact, by the application of several excitatory amino acid antagonists or by increasing Mg2+ so that the efficacy of synaptic transmission was reduced. All synchronized activity was suppressed by applying an increased concentration of antagonist or by raising Mg2+ and lowering Ca2+ so that synaptic transmission was completely blocked. This synchronized neuronal activity occurred spontaneously in the CA2-3 region when isolated from the CA1 pyramidal cell area and the dentate gyrus. When CA2 was separated from CA3 a synchronized rhythm of single bursts was observed in CA2, while a different, slower, synchronized population discharge consisting of initial bursts followed by afterdischarges occurred in CA3. The smallest completely isolated segments of the CA3 field which spontaneously generated synchronized afterdischarges, comparable to those observed in the intact slice, measured 500-700 microns along the stratum pyramidable. It is concluded that these afterdischarges depend on local neuronal interactions mediated by chemical synaptic mechanisms which may occur within a single population of as few as 1000 CA3 pyramidal cells. The results are consistent with a repeated activation of the same group of synapses, which may release an excitatory amino acid neurotransmitter, being responsible for the initiation of each afterdischarge.

Action Potentials↗
PubMed1984

Synchronized afterdischarges in the hippocampus: simulation studies of the cellular mechanism.

Synchronized multiple bursts represent an epileptic neuronal behavior transitional between synchronized single bursts (interictal spikes) and self-sustained seizures. As described in the previous paper, synchronized multiple bursts occur in hippocampal slices treated with picrotoxin. Multiple bursts consist of an initial prolonged depolarizing burst followed by a rhythmical series of afterdischarges. Both the initial burst and the afterdischarges are synaptically elicited. Our previously described model of the interictal spike illustrates that the generation of a single synchronized burst requires a neuronal network possessing the following properties: intrinsic bursting capability of individual neurons, the presence of recurrent excitatory connections between principal neurons and the blockade of synaptic inhibition. The model demonstrates that the generation of single synchronized bursts involves the initial excitation of one or more neurons, and the subsequent sequential spread of excitation through a population of neurons via recurrent excitatory synapses. In the present study, we examined whether this same mechanism assumed in the previous model could also allow for the generation of synchronized afterdischarges in a population of neurons. We tested the effects of manipulating three network factors: synaptic strength, synaptic density and the refractoriness in the population members following a period of excitation. We discovered that the refractory period following prolonged excitation assumed in our previous model was insufficient to allow for afterdischarge generation. Once sufficient refractoriness was introduced, afterdischarges appeared in our network of neurons. In the present study, the required refractoriness was attributed to the properties of pyramidal cell axons. In principle, such refractoriness might be located elsewhere in the network. The possible contribution of axonal properties is emphasized because of the known intermittent conduction in other axons. Our present model also reproduced other experimental data. Thus, if the network was too small or if synaptic strength was too small, then only a single synchronized burst occurred. The basic assumptions of this model are both biologically plausible and experimentally testable.

Action Potentials↗
PubMed1984

Local circuit interactions in synchronization of cortical neurones.

Under certain circumstances large numbers of neurones in the mammalian central nervous system (CNS) can discharge simultaneously. An example of such activity is recorded from a hippocampal slice in the presence of agents which block synaptic inhibition. This synchronized discharge occurs spontaneously in a rhythmic fashion or may be triggered by stimulation of any afferent pathway. Its generation appears to involve local circuit interactions. The favourable conditions offered by an in vitro preparation have allowed the cellular events during this activity to be examined in some detail. Three factors appear to be critically involved in the synchronization process. Firstly, the intrinsic ability of neurones to generate bursts, secondly, the existence of powerful recurrent excitatory connections, and thirdly the absence of inhibition which normally prevents the spread of bursting activity through the recurrent connections. Computer simulations show that in a sparsely connected network of bursting neurones activity initiated in a few cells may spread through recurrent connections until eventually the whole population discharges simultaneously. Rhythmic discharges similar to those described here also underly various CNS functions including centrally-originating motor patterns. It remains to be determined whether neuronal properties and connectivity found to be important in this hippocampal rhythm may also play a role in the generation of other rhythmic activities in the mammalian CNS.

Animals↗
PubMed1983

Cellular mechanisms underlying the inhibitory surround of penicillin epileptogenic foci.

Penicillin applied locally to the surface of in vivo hippocampus or neocortex is known to produce not only periodic interictal spikes within a focus, but also altered cellular activities around the focus. In the zone adjacent to a hippocampal focus, for example, Dichter and Spencer recorded hyperpolarization-depolarizing burst-hyperpolarization sequences, while further from the focus they recorded only hyperpolarizations (presumably IPSPs). We use here our previously developed model of interictal spike generation to show that these observations can be explained by the following two assumptions: (1) there is a gradient of effectiveness of synaptic inhibition (small within the focus and increasing with distance from the focus) caused by the gradient of penicillin concentration; and (2) the radius for recurrent inhibition is larger than the radius for recurrent excitation. Our model best fits the experimental data if we assume further that recurrent excitation extends from any one small cortical region to only some--not all--of its neighboring regions.

Computers↗
PubMed1983

Synaptic mechanisms underlying interictal spike initiation in a hippocampal network.

The intrinsic bursting capability of hippocampal neurons is well established. Recent experimental data also imply that CA3 neurons have mutual chemical excitatory interactions. Our previous simulations have shown how these two properties of the hippocampal CA3 region suffice to account for the synchronized burst discharges that occur in the presence of penicillin. Electrotonic interactions via gap junctions have also been described in the CA3 region, but their contribution to synchronization is not clear. We now show that a network of cells connected only by electrotonic junctions does not reproduce the experimental data on synchronization. In combination with chemical synapses, electrotonic junctions can prevent synchronized discharge, increase the degree of synchronization, or prolong the latency from stimulus to discharge. The effect electrotonic junctions have on synchronization of cellular bursting depends intimately on the density and strength of the chemical synapses.

Action Potentials↗
PubMed1982

Cellular mechanism of neuronal synchronization in epilepsy.

Interictal spikes are a simple kind of epileptic neuronal activity. Field potentials and intracellular recordings observed during interictal spikes of penicillin-treated slices of the hippocampus were reproduced by a mathematical model of a network of 100 hippocampal neurons from the region including CA2 and CA3. The model shows that this form of neuronal synchronization arises because of mutual excitation between neurons, each of which is capable of intrinsic bursting in response to a brief input.

Action Potentials↗
PubMed1982

Simulation of intrinsic bursting in CA3 hippocampal neurons.

Dendritic recordings from hippocampal pyramidal cells suggest that bursts of action potentials--riding on a depolarizing wave and terminating in a slow calcium-mediated spike--can be generated locally in the dendrites, as well as at the soma. These data necessitated revision of our earlier model in which bursts at the soma are generated by interaction of two spatially separated conductance systems--a fast-spike sodium mechanism at the soma and a slow-spike calcium mechanism on the apical dendrite. We have introduced into a model of the CA3 hippocampal neuron two experimentally testable concepts: voltage-dependent inactivation of Ik and partial inactivation of ICa by Ca2+ ion. With these mechanisms, the model accurately reproduces bursts generated in either soma or in the apical dendrites by sets of conductances all located in the same respective membrane region. The model is also capable of bursting repetitively in response to continuous stimulation.

Axons↗