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R D Traub

Publications and source records attributed to R D Traub.

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

Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation.

Partially synchronous 40-Hz oscillations of cortical neurons have been implicated in cognitive function. Specifically, coherence of these oscillations between different parts of the cortex may provide conjunctive properties to solve the 'binding problem': associating features detected by the cortex into unified perceived objects. Here we report an emergent 40-Hz oscillation in networks of inhibitory neurons connected by synapses using GABAA (gamma-aminobutyric acid) receptors in slices of rat hippocampus and neocortex. These network inhibitory postsynaptic potential oscillations occur in response to the activation of metabotropic glutamate receptors. The oscillations can entrain pyramidal cell discharges. The oscillation frequency is determined both by the net excitation of interneurons and by the kinetics of the inhibitory postsynaptic potentials between them. We propose that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.

Action Potentials↗
PubMed1995

Model of synchronized population bursts in electrically coupled interneurons containing active dendritic conductances.

We constructed a computer model of 128 interneurons, each with multiple dendritic branches and an axonal segment. The model neurons were interconnected by gap junctions between dendritic compartments, as are known to occur in rat and guinea-pig hilar interneurons. The model contained no excitatory synapses. In the presence of low-frequency spontaneous action potentials, the model generated synchronized population bursts, when gap junction resistance was 50 M omega and there were at least two gap junctions per neuron on average. Population bursts occurred only when the dendrites of model neurons were electrically excitable. Consistent with experiment, somatic hyperpolarization during the population burst uncovered partial spikes. In the model, partial spikes originated in electrically active dendrites driven by coupled dendrites. This model may account for population bursts in hilar interneurons that occur in 4-aminopyridine (4AP) together with blockers of GABAA and excitatory amino acid (EAA) receptors.

Action Potentials↗
PubMed1995

Pyramidal cell-to-inhibitory cell spike transduction explicable by active dendritic conductances in inhibitory cell.

In the guinea-pig hippocampal CA3 region, the synaptic connection from pyramidal neurons to stratum pyramidale inhibitory neurons is remarkable. Anatomically, the connection usually consists of a single release site on an interneuronal dendrite, sometimes 200 microns or more from the soma. Nevertheless, the connection is physiologically powerful, in that a single presynaptic action potential can evoke, with probability 0.1 to 0.6, a postsynaptic action potential with latency 2 to 6 ms. We construct a model interneuron and show that the anatomical and physiological observations can be reconciled if the interneuron dendrites are electrically excitable. Excitable dendrites could also account for depolarization-induced amplification of the pyramidal cell-interneuron EPSP in the voltage range subthreshold for spike generation.

Action Potentials↗
PubMed1994

A branching dendritic model of a rodent CA3 pyramidal neurone.

1. We constructed a branching dendritic compartmental model of a CA3 pyramidal neurone, using experimental data from guinea-pig and rat cells obtained in vitro. The goal was to understand interactions between synaptic events impinging on dendritic branches and voltage- and calcium-dependent currents. The model contained sixty-four soma-dendrite (SD) compartments, an axon initial segment (IS), and four axonal compartments. There were six active conductances in the SD membrane, including a sodium conductance (gNa) and a high-threshold calcium conductance (gCa), with kinetic properties similar to those reported in a previous study. 2. The distribution of conductance densities across the IS and SD was adjusted by testing the model response to antidromic stimulation and current pulses or sustained currents injected into the soma or apical dendrites. As before, gNa was concentrated on and near the soma with lower density in the dendrites, while gCa had a higher density in apical dendrites than at the soma. 3. The model predicts that CA3 pyramidal neurones in media blocking synaptic transmission should fire a burst of action potentials following antidromic stimulation. This was confirmed experimentally in hippocampal slices. 4. Both in the model and in guinea-pig neurones, dendritic IPSCs can delay the onset of bursting. If an IPSC begins soon enough after the first fast action potential, the later burst envelope is attenuated. This effect results from suppression of dendritic Ca2+ electrogenesis. 5. The model predicts that an appropriately timed dendritic IPSC (after the first somatic spike but before the dendritic Ca2+ spike) may suppress the transient local [Ca2+] signal, while having a negligible effect on the electrical output of the neurone. This phenomenon has been reported in guinea-pig Purkinje cells. 6. We conclude that active dendritic currents are critical for regulation of the electrical output of CA3 pyramidal neurones. We suggest also that dendritic [Ca2+] signals might be controlled in individual dendrites independently of action potential outputs, an effect of possible importance for synaptic plasticity.

Action Potentials↗
PubMed1994

Enhanced NMDA conductance can account for epileptiform activity induced by low Mg2+ in the rat hippocampal slice.

1. Why does lowering extracellular Mg2+ cause synchronous neuronal bursts and after-discharges? To address this question, a computer model of the CA3 region was constructed with 1000 pyramidal neurones and 100 inhibitory neurones. Pyramidal neurones were multicompartmental and contained five ionic conductances, distributed non-uniformly on the membrane. In parallel, experiments were performed on rat hippocampal slices perfused in solutions without added Mg2+. 2. Model neurones were interconnected randomly as follows. Recurrent excitatory connections between pyramidal neurones, and from pyramidal neurones to inhibitory cells, stimulated both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (rapid, voltage and Mg2+ independent) and NMDA receptors (slow conductance decay, voltage and Mg2+ dependent). A time-dependent 'desensitization' process was included whereby the NMDA-mediated conductance declined after the onset of synchronized firing. Half of the inhibitory neurones activated GABAA receptors on pyramidal cells (perisomatic, rapid), and half activated GABAB receptors (dendritic, slow onset and decay). 3. We examined patterns of synchronous firing in the pyramidal cells as parameters defining model features were manipulated. These parameters included the maximum conductance of individual synapses, [Mg2+]o, excitatory connectivity, and parameters that defined the NMDA 'desensitization' process. Comparisons were made with experiment where possible. 4. GABAA blockade in 1 mM [Mg2+]o induces single bursts and bursts with after-discharges. Synchronized bursts and after-discharges also occurred in the model when NMDA conductances were sufficiently enhanced, even with GABAA inhibition present. Both in simulated and experimental after-discharges in low-Mg2+ solutions, the level of GABAA inhibition was important in determining the number of secondary bursts and the number of somatic spikes per wave. 5. The model of low-Mg(2+)-induced synchrony predicts that each somatic wave is induced by a dendritic Ca2+ spike and that the dendritic spikes are superimposed on a tonic dendritic depolarization generated by the enhanced NMDA conductance. We further predict the recurrent activation of interneurones by NMDA receptors, based both on experiments and simulations in which AMPA receptors are blocked. 6. Many of the mechanisms underlying low-Mg(2+)-induced after-discharges appear to resemble those underlying picrotoxin-induced after-discharges. These mechanisms can operate in low-Mg2+ solutions because of the increase in NMDA conductance in the recurrent excitatory connections.

Animals↗
PubMed1994

Are there unifying principles underlying the generation of epileptic afterdischarges in vitro?

To find general principles in the cellular mechanisms of epileptogenesis, one must analyze experimental epilepsy models and determine what exists in common between them. We consider here afterdischarges in hippocampal slices induced using either (1) GABAA blockade (e.g. with bicuculline), (2) a bathing solution lacking Mg2+ ions (low Mg-induced epilepsy), or (3) 4-aminopyridine (4AP). By 'afterdischarge' we mean an event that lasts hundreds of milliseconds or more, involving the synchronous firing of all the neurons in a population, shaped into a long initial burst and a series of one or more secondary bursts, and terminating in a prolonged afterhyperpolarization (AHP). We propose that the following features exists in common between these three experimental epilepsies: (1) recurrent excitatory synaptic connections; (2) sustained dendritic synaptic excitation, mediated by either AMPA or NMDA receptors, or both; (3) an intrinsic cellular response to sustained excitation, consisting of rhythmical dendritic bursts, primarily mediated by Ca spikes. In conclusion, if the picture outlined here proves correct, then the stereotypic appearance of epileptic afterdischarges--consisting of synchronized population bursts in series, whatever the network alteration leading to seizures--does indeed reflect a common set of mechanisms. The mechanisms cannot, apparently, be formulated in simple terms of this receptor or that receptor. Rather, we suggest, the recurrent excitatory synapses are able, under diverse circumstances, collectively to produce sustained dendritic conductances in neuronal populations. Pyramidal neurons, by virtue of their normal intrinsic membrane properties, respond to such sustained conductances with rhythmical bursts. The recurrent synapses, in a dual role, serve to maintain the synchrony of these bursts, and so shape the activity into a synchronized oscillation.

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PubMed1993

Synaptic and intrinsic conductances shape picrotoxin-induced synchronized after-discharges in the guinea-pig hippocampal slice.

1. A computer model was constructed of the guinea-pig hippocampal region in vitro, containing 100 pyramidal neurones. This approach has contributed to the understanding of brief (usually less than 100 ms) epileptic events known as 'interictal spikes'. The present study addresses the cellular mechanisms of more prolonged epileptic events, lasting 200 ms and more, that may represent short-duration seizures. Each neurone was simulated with a nineteen-compartment model using six voltage-dependent ionic conductances. The neurones were randomly interconnected with excitatory synapses, each synapse exerting a fast voltage-independent alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) component and a slower voltage-dependent N-methyl-D-aspartate (NMDA) component. Each neurone received input from twenty other neurones. 2. This model was able to generate, in response to synaptic noise or to stimulation of one neurone, a series of synchronized population bursts, the initial (primary) burst being longer than later (secondary) bursts, terminating in a prolonged after-hyperpolarization. The simulated after-discharge potentials resemble those recorded experimentally from pyramidal neurones during perfusion of the hippocampal slice with media containing picrotoxin, a blocker of synaptic inhibition mediated by GABAA receptors. 3. Simulated after-discharges agree with the following experiments: over a certain range of total NMDA conductance, blockade of AMPA receptors will prevent the occurrence of synchronized firing, whereas, blockade of NMDA receptors will, in contrast, abolish the secondary bursts, leaving a shortened and somewhat smaller primary burst. Dendritic potential oscillations occur in phase with somatic oscillations. When interneurones (some generating GABAA-mediated IPSPs, others generating GABAB IPSPS) are included in the model, the occurrence of synchronized events was suppressed, the most significant suppressant effect coming from GABAA IPSPS. 4. The model predicts that: a dendritic calcium spike occurs during each secondary burst; AMPA receptors serve to maintain the synchrony of secondary bursts, as well as to initiate the primary burst; and that with sufficient total NMDA conductance, synchronized firing can occur even with AMPA receptors blocked. 5. The model suggests, in addition, that the duration of the initial burst is determined in part by the experimentally observed delay between Ca2+ entry and peaking of the after-hyperpolarization (AHP) conductance, and hence reflects properties of the individual pyramidal neurones. Specifically, a pattern of a long initial burst followed by brief secondary bursts is elicited in single-cell simulations by injection of a steady depolarizing current into the apical dendrite. The same pattern is produced when the single-cell model includes only calcium and calcium-dependent conductances.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Analysis of the propagation of disinhibition-induced after-discharges along the guinea-pig hippocampal slice in vitro.

1. A model has been proposed of picrotoxin-induced hippocampal in vitro after-discharges; it depends critically upon alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the recurrent excitatory connections between pyramidal neurones, and upon the ability of pyramidal neurones to generate bursts at about 10 Hz when their dendrites are sufficiently depolarized. 2. We study here the question of whether this model can account for spatial--as well as temporal--aspects of after-discharges in guinea-pig hippocampal slices. For example, can the model explain the propagation along a transverse slice of the initial burst and the secondary bursts at about the same velocity, approximately 0.10-0.20 m s-1? Under what conditions might the secondary bursts exhibit a different spatial pattern to the initial burst, as we now show can occur in longitudinal slices? To examine these questions, we increased the number of cells in our model from 100 to 8000 (in a 20 x 400 array), arranging the excitatory synaptic connections in a spatially restricted fashion, with an average extent of 1.0 mm (as suggested experimentally). 3. Our model suggests that both AMPA and NMDA receptors contribute to the propagation pattern and velocity of the initial and the secondary bursts in an after-discharge. 4. When unitary AMPA and NMDA conductances are in the range where the primary burst lasts for 100-200 ms, and there are three or four secondary bursts, then both primary and secondary bursts propagate near to the experimentally observed velocity for transverse slices. In the model, however, secondary bursts propagate at somewhat slower velocities than the initial burst. 5. The mechanisms of propagation are different for the initial and for the secondary bursts: propagation of the primary burst depends upon the initiation of electrogenesis in 'resting' dendrites by AMPA and NMDA inputs that are rapidly increasing in time. Propagation of secondary bursts depends upon the timing of calcium spikes in depolarized dendrites with slowly varying NMDA inputs; the timing of calcium spikes can be influenced by a 'wave' of AMPA input, but calcium spikes--we predict--should occur even without the AMPA input, once the after-discharge has been initiated. The blockade of firing in an intermediate region of the disinhibited slice is predicted to have different effects on the primary burst and on secondary bursts distal to the region of blockade.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Computer simulation of carbachol-driven rhythmic population oscillations in the CA3 region of the in vitro rat hippocampus.

1. We used simulations of the in vitro CA3 region of the hippocampus to analyse the 5 Hz population oscillations recorded experimentally in carbachol. 2. A simulation model of the in vitro CA3 region was constructed with 1000 pyramidal neurones and 200 inhibitory neurones (100 producing fast inhibitory postsynaptic potentials (IPSPs) and 100 producing slow IPSPs of delayed onset). Each neurone contained nineteen soma-dendritic compartments. Pyramidal neurones contained six voltage- and/or calcium-dependent ionic currents, whose kinetics were consistent with voltage-clamp data. The connectivity and waveform of unitary synaptic events for excitatory and fast inhibitory synapses were consistent with dual intracellular recordings. This network was shown to generate previously described network oscillations, including synchronized bursts recorded in the presence of GABAA blockers, and synchronized synaptic potentials observed during partial blockade of GABAA inhibition. 3. The model generated 5 Hz oscillations as recorded in carbachol under the following conditions: (a) excitatory synaptic conductance was within a limited range; (b) there was blockade of fast and slow IPSPs (consistent with the experimental lack of effect of bicuculline and phaclofen on carbachol oscillations and the known depression of IPSPs by acetylcholine); (c) the after hyperpolarization (AHP) conductance was reduced (consistent with the known pharmacology of carbachol); (d) the apical dendrites of the pyramidal cells were depolarized, as suggested by the carbachol-induced depolarization of pyramidal neurones. Each oscillation was associated in pyramidal cells with a burst of action potentials riding on a depolarizing wave. The N-methyl-D-aspartate (NMDA) type of excitatory synapse was not necessary for the oscillations to occur. 4. Progressive reduction of excitatory synaptic strength led to an oscillation of the same frequency, with bursts riding on smaller EPSPs (consistent with the experiment). Further reduction of excitatory synaptic strength abolished the population oscillation by uncoupling the neurones. When excitatory synaptic conductance was too large, population oscillations were attenuated as the cells switched from a bursting mode to a repetitively firing mode. 5. Increasing the AHP conductance prolonged the interburst interval as expected. Inclusion of slow IPSPs exerted a similar effect. 6. When fast IPSPs were included, an oscillation with different characteristics emerged: a 10 Hz oscillation that was gated by compound GABAA IPSPs. On any oscillatory wave, few pyramidal neurones fired, and the firing of individual neurones was irregular.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1991

A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances.

1. We have developed a 19-compartment cable model of a guinea pig CA3 pyramidal neuron. Each compartment is allowed to contain six active ionic conductances: gNa, gCa, gK(DR) (where DR stands for delayed rectifier), gK(A), gK(AHP), and gK(C). THe conductance gCa is of the high-voltage activated type. The model kinetics for the first five of these conductances incorporate voltage-clamp data obtained from isolated hippocampal pyramidal neurons. The kinetics of gK(C) are based on data from bullfrog sympathetic neurons. The time constant for decay of submembrane calcium derives from optical imaging of Ca signals in Purkinje cell dendrites. 2. To construct the model from available voltage-clamp data, we first reproduced current-clamp records from a model isolated neuron (soma plus proximal dendrites). We next assumed that ionic channel kinetics in the dendrites were the same as in the soma. In accord with dendritic recordings and calcium-imaging data, we also assumed that significant gCa occurs in dendrites. We then attached sections of basilar and apical dendritic cable. By trial and error, we found a distribution (not necessarily unique) of ionic conductance densities that was consistent with current-clamp records from the soma and dendrites of whole neurons and from isolated apical dendrites. 3. The resulting model reproduces the Ca(2+)-dependent spike depolarizing afterpotential (DAP) recorded after a stimulus subthreshold for burst elicitation. 4. The model also reproduces the behavior of CA3 pyramidal neurons injected with increasing somatic depolarizing currents: low-frequency (0.3-1.0 Hz) rhythmic bursting for small currents, with burst frequency increasing with current magnitude; then more irregular bursts followed by afterhyperpolarizations (AHPs) interspersed with brief bursts without AHPs; and finally, rhythmic action potentials without bursts. 5. The model predicts the existence of still another firing pattern during tonic depolarizing dendritic stimulation: brief bursts at less than 1 to approximately 12 Hz, a pattern not observed during somatic stimulation. These bursts correspond to rhythmic dendritic calcium spikes. 6. The model CA3 pyramidal neuron can be made to resemble functionally a CA1 pyramidal neuron by increasing gK(DR) and decreasing dendritic gCa and gK(C). Specifically, after these alterations, tonic depolarization of the soma leads to adapting repetitive firing, whereas stimulation of the distal dendrites leads to bursting. 7. A critical set of parameters concerns the regulation of the pool of intracellular [Ca2+] that interacts with membrane channels (gK(C) and gK(AHP)), particularly in the dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Role of EPSPs in initiation of spontaneous synchronized burst firing in rat hippocampal neurons bathed in high potassium.

1. Spontaneous discharges that resemble interictal spikes arise in area CA3 b/c of rat hippocampal slices bathed in 8.5 mM [K+]o. Excitatory postsynaptic potentials (EPSPs) also appear at irregular intervals in these cells. The role of local synaptic excitation in burst initiation was examined with intracellular and extracellular recordings from CA3 pyramidal neurons. 2. Most (70%) EPSPs were small (less than 2 mV in amplitude), suggesting that they were the product of quantal release or were evoked by a single presynaptic action potential in another cell. It is unlikely that most EPSPs were evoked by a presynaptic burst of action potentials. Indeed, intrinsic burst firing was not prominent in CA3 b/c pyramidal cells perfused in 8.5 mM [K+]o. 3. The likelihood of occurrence and the amplitude of EPSPs were higher in the 50-ms interval just before the onset of each burst than during a similar interval 250 ms before the burst. This likely reflects increased firing probability of CA3 neurons as they emerge from the afterhyperpolarization (AHP) and conductance shunt associated with the previous burst. 4. Perfusion with 2 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a potent quisqualate receptor antagonist, decreased the frequency of EPSPs in CA3 b/c neurons from 3.6 +/- 0.9 to 0.9 +/- 0.3 (SE) Hz. Likewise, CNQX reversibly reduced the amplitude of evoked EPSPs in CA3 b/c cells. 5. Spontaneous burst firing in 8.5 mM [K+]o was abolished in 11 of 31 slices perfused with 2 microM CNQX.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Model of synchronized epileptiform bursts induced by high potassium in CA3 region of rat hippocampal slice. Role of spontaneous EPSPs in initiation.

1. We constructed a computer model of the in vitro CA3 region of the rat hippocampal slice bathed in a high-potassium medium. Our aim was to understand better the mechanisms of initiation of synchronized bursts and the processes that regulate the interburst interval in the experimental system. 2. Our model began with a previously published model of the longitudinal CA3 hippocampal slice. The model contains three interconnected cell populations: 9,000 (excitatory) pyramidal cells; 450 inhibitory cells whose postsynaptic action is somatic and decays quickly, corresponding to chloride-dependent inhibition mediated by gamma-aminobutyric acid (GABA)A channels, and 450 inhibitory cells whose postsynaptic action is dendritic, of delayed onset and long lasting, that corresponds to K-dependent inhibition mediated by GABAB channels. 3. The model was then modified to account for specific features of the high-K experimental system: 1) the pyramidal cells do not generate intrinsic bursts; 2) EIPSP(CI) and EK are both shifted in a depolarizing direction; 3) spontaneous (i.e., not caused by presynaptic firing) excitatory postsynaptic potentials (EPSP)s were included; and 4) a steady current was injected into the pyramidal cells to depolarize them. 4. This model generates synchronized population bursts with interburst intervals of approximately 1.0-1.5 s. Bursts in individual pyramidal cells are preceded by barrages of EPSPs. These results agree with experiment. 5. Our model agrees with the following additional experiments: 1) synchronized bursts are abolished by partial blockade of excitatory synapses; 2) burst frequency is increased by partial blockade of a slow-intrinsic-K conductance; and 3) blockade of chloride-dependent inhibition leads to bursts of longer duration with longer interburst intervals. 6. The basic structural features of this model are similar to, but not identical to, the model of the disinhibited hippocampal slice. Spontaneous EPSPs appear to be critical in the high-K system for initiating, but not for synchronizing, population bursts. The experimental data and simulation results raise interesting questions about the role of spontaneous EPSPs in initiating synchronized discharges in other epileptic systems and on the possible role of spontaneous EPSPs in the normal brain.

Action Potentials↗
PubMed1989

Model of the origin of rhythmic population oscillations in the hippocampal slice.

One goal of mammalian neurobiology is to understand the generation of neuronal activity in large networks. Conceptual schemes have been based on either the properties of single cells or of individual synapses. For instance, the intrinsic oscillatory properties of individual thalamic neurons are thought to underlie thalamic spindle rhythms. This issue has been pursued with a computer model of the CA3 region of the hippocampus that is based on known cellular and synaptic properties. Over a wide range of parameters, this model generates a rhythmic activity at a frequency faster than the firing of individual cells. During each rhythmic event, a few cells fire while most other cells receive synchronous synaptic inputs. This activity resembles the hippocampal theta rhythm as well as synchronized synaptic events observed in vitro. The amplitude and frequency of this emergent rhythmic activity depend on intrinsic cellular properties and the connectivity and strength of both excitatory and inhibitory synapses.

Animals↗
PubMed1988

Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus.

1. Mechanisms underlying the propagation of synchronous epileptiform activity in disinhibited hippocampal slices were examined in experimental and computer simulation studies. 2. Experiments were performed with longitudinal slices of the CA3 region. Synchronous firing was initiated by stimulating stratum radiatum fibers in the presence of picrotoxin. It propagated smoothly and without decrement at velocities close to 0.15 m/s over distances up to 10 mm. 3. In elevated extracellular calcium, neuronal firing threshold was increased and synchronous burst firing did not spread. Monophasic excitatory postsynaptic potentials (EPSPs) were recorded in cells at limited distances from a stimulus in the presence of 10 mM Ca and picrotoxin. Axonal conduction velocity, estimated from EPSP latencies, was several times faster than the spread of synchronous firing. 4. EPSPs recorded in 5-7 mM Ca and picrotoxin could consist of two components. The properties of the first component were similar to those of synaptic events recorded in 10 mM Ca. The second component was of longer latency and unlike the first component was suppressed in responses to paired stimuli at interval 50-300 ms. Recordings from cells at different distances from a stimulus suggested that the second component spread further and more slowly than the first component. 5. In computer simulations the CA3 region was represented by a spatially distributed network of 9,000 excitatory neurons and 900 inhibitory cells. Individual cells and synapses had properties based on experimental data. The effects of varying synaptic strength and connectivity on the spread of activity in the model was examined. 6. When synaptic inhibition was functional in simulations, firing was restricted to a single action potential in model cells close to the stimulus, as in experiments. Synchronous burst firing spread throughout the neuronal array when fast synaptic inhibition was absent. The velocity of propagation was slower than conduction in simulated axons when synaptic contacts made by excitatory cells were spatially limited. Propagation velocity increased with increases in the spatial extent of excitatory connectivity. 7. Increasing the threshold of neurons in a region of the model network reduced the speed at which synchronous firing spread. In experiments focal application of gamma-aminobutyric acid (GABA) elevated neuronal firing threshold and slowed the propagation of synchrony in a local region. 8. As the strength of synaptic inhibition was gradually reduced, neuronal activity spread further and faster through the simulated neuronal network.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

The initiation and spread of epileptiform bursts in the in vitro hippocampal slice.

We recorded spontaneous synchronized epileptiform bursts from hippocampal slices from guinea pig using an array of 16 extracellular electrodes placed over the stratum pyramidale of CA2 and CA3. The slices were made epileptogenic with the GABA antagonist picrotoxin (or occasionally penicillin). We found that spontaneous bursts always originate at a discrete focus at or near CA2. These bursts spread smoothly and uniformly across CA3 at an average velocity of 0.13 m/s. This velocity is slower than the conduction velocity of the Schaffer collaterals or mossy fibers. Picrotoxin produced afterdischarges following the initial primary burst, and these afterdischarges were found to originate and spread in a fashion nearly identical to the primary burst. These results indicate that CA2 is a unique region which must possess unusual cellular and/or synaptic connectivity properties which result in a decreased threshold for initiation of epileptiform activity. We consider several hypothetical patterns of local synaptic connectivity in the light of these results, and we discuss the possible role of residual inhibition in limiting the spread of synchronized discharges.

Animals↗
PubMed1987

Models of the cellular mechanism underlying propagation of epileptiform activity in the CA2-CA3 region of the hippocampal slice.

We have shown experimentally in the previous paper that spontaneous epileptiform activity, as recorded by extracellular field potentials, propagates smoothly across the CA2-CA3 region of the convulsant-treated hippocampal slice of the guinea pig at velocities of about 0.1 m/s. In the present paper, we used computer simulations of either 500 or 1000 cell arrays of model neurons to examine possible mechanisms underlying this propagation. We show that propagation of epileptiform field potentials can be explained plausibly by slow conduction along axons interconnecting CA2-CA3 neurons, provided that there are sufficiently many interconnections. This propagation can take place even if the interconnections occur randomly. The number of interconnections required decreases as the number of synchronously activated cells initiating a population burst increases. Axonal propagation at 0.1 m/s appears to be a plausible assumption, since conduction velocities along Schaffer collaterals have been experimentally estimated to be as slow as 0.2 m/s, and small recurrent collaterals are likely to conduct more slowly than the main axonal branches. If spontaneous synchronized population bursts are initiated by activity in four or fewer cells, then our model requires, for smooth field potential propagation, more interconnections than are believed to occur on the basis of dual intracellular recording.

Animals↗