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PubMed2000

Assessment of corticodiaphragmatic pathway and pulmonary function in acute ischemic stroke patients.

This study investigates the effect of stroke on the corticodiaphragmatic pathway and attempts to clarify the relationship between neurophysiological data and degree of motor disability, site of infarction in computerized tomography (CT) scan, diaphragmatic excursion, blood gases and pulmonary function in stroke patients. Using magnetic stimulation of the scalp sites and cervical roots, an assessment of corticodiaphragmatic pathway was made. The study included 34 sequentially selected patients from a total of 250 patients with acute ischemic stroke. Twenty-five (age- and sex-matched) volunteers served as controls. Sixteen patients had cortical infarction, 13 had subcortical infarction and five had both cortical and subcortical infarction. The mean according to the Scandinavian Stroke Scale was 32.2. Decreased diaphragmatic excursion was observed in 41% of the patients. Twenty-four patients (70.5%) had abnormal magnetic evoked potentials (MEPs) in the affected hemisphere. In five patients MEPs could not be elicited from the affected hemisphere; the remaining 19 patients had abnormal values of both cortical latency and central conduction time (CCT). Cortical latency, CCT, amplitude of compound muscle action potentials (CMAPs) and excitability threshold of the affected hemisphere were significantly altered compared with both the unaffected hemisphere and the control group. Those patients with hemiplegia had a greater degree of hypoxia, hypocapnia and decreased serum bicarbonate level compared with the control group. Also, hemiplegic patients had different degree of respiratory dysfunction. A statistically significant association was found between neurophysiological data and disability score, diaphragmatic excursion, site of infarction in CT scan and degree of respiratory dysfunction. Central diaphragmatic impairment may occur in acute stroke and could contribute to the occurrence of hypoxia in those patients.

Action Potentials↗
PubMed1986

Postsynaptic potentials evoked in spiny neostriatal projection neurons by stimulation of ipsilateral and contralateral neocortex.

Postsynaptic potentials were evoked in neostriatal neurons by stimulation of the ipsilateral and contralateral medial agranular frontal cortical field (AGm) in the rat. This cortical region is known to project bilaterally to the dorsal lateral head of the caudate-putamen of rats. Ipsilateral stimulation of AGm should excite all types of corticostriatal neurons projecting to neostriatal neurons in the corresponding area in neostriatum, while stimulation of the same cortical area on the side contralateral to the recording should evoke synaptic potentials from a more restricted subpopulation of crossed corticostriatal neurons. Neostriatal neuronal responses were recorded intracellularly and spiny projection neurons identified by intracellular staining with horseradish peroxidase. The initial EPSP response to contralateral stimulation was similar to that evoked from the ipsilateral side, except for the absence of a relatively small short latency component responsible for the earliest part of the response to ipsilateral cortical stimulation. Comparison with previous findings indicated that this earliest EPSP component was due to activation of fast-conducting descending cortical efferents with collateral projections exclusively to the ipsilateral neostriatum. Stimulation of contralateral neostriatum evoked responses identical to those obtained using stimulation of contralateral neocortex. Analyses of these responses indicated that both EPSPs arise from activation of the same population of fibers. Stimulation of the contralateral internal capsule just caudal to neostriatum was not effective in evoking the EPSP. Chronic hemidecortication did not change the shape of the EPSP evoked from the intact contralateral side, but reduced its amplitude by approximately one half. These observations indicate that contralaterally projecting corticostriatal neurons in the rat project bilaterally in neostriatum, have axonal branches to the contralateral cerebral cortex as well as neostriatum, and converge onto neostriatal neurons that also receive input from the corresponding cortical region on the ipsilateral side.

Animals↗
PubMed2003

Depression of mGluR-mediated IPSCs by 5-HT in dopamine neurons of the rat substantia nigra pars compacta.

Dopamine neurons of the substantia nigra pars compacta receive a prominent serotonin (5-HT) projection from the dorsal raphe nucleus and important functional interactions between the serotonergic and the dopaminergic system have been postulated. In the present report we examined the role of 5-HT in the modulation of the metabotropic glutamate receptor-mediated inhibitory postsynaptic current (mGluR-IPSC) in midbrain dopamine neurons, and we found a reversible depression of this synaptic response at concentrations of 5-HT ranging from 100 nm to 30 microm (EC50 1.06 microm). This resulted in a shift towards excitation of the overall dopamine neuron response to glutamatergic synaptic input. This effect was not because of a direct modulation of the Ca2+-sensitive K+ conductances underlying the mGluR-IPSC, but was associated with a decrease in the intracellular calcium signal triggered by mGluR stimulation. Similar results were obtained with alpha-methyl-5-hydroxytryptamine and 5-methoxytryptamine, but not with 5-carboxamidotryptamine or 1-(3-chlorophenyl) piperazine. No significant depression of the mGluR-IPSC by 5-HT was observed in the presence of the 5-HT2 antagonist cinanserin or the 5-HT4 receptor antagonist RS 23597-190, whereas the 5-HT2C antagonist RS 102221 was ineffective. Our results demonstrate a powerful inhibition of the mGluR-IPSC by 5-HT in midbrain dopamine neurons, most probably through stimulation of 5-HT2A and 5-HT4 receptors.

Animals↗
PubMed1994

Correlation of somatosensory central conduction time with height.

To study the correlation between somatosensory central conduction time (CCT) and the subject's height, we recorded somatosensory evoked potentials (SEPs) from the neck and scalp elicited by median nerve stimulation in 72 normal young adults. We determined the CCT in each subject from peak-to-peak and onset-to-onset measurements. The mean value for the onset CCT was 6.2 +/- 0.4 msec and for the peak CCT, 5.7 +/- 0.5 msec. The peak CCT was significantly shorter but showed a wide range. There was a significant correlation between the onset CCT, but not the peak CCT, and height. Our findings confirm that the length of the central somatosensory pathway is proportional to the subject's height and indicate that the "conventional" peak CCT measurement of median nerve SEPs is inadequate.

Adolescent↗
PubMed1976

Inhibitory potentials produced in cortical cells by stimulation of the lateral hypothalamus in rabbits.

(1) Intracellular potentials were recorded from pyramidal tract (PT) and non-pyramidal tract (non-PT) cells of the frontal cortex in urethane-anesthetized rabbits and the effects of electrical stimulation of the lateral hypothalamus (LH) were examined on the ipsilateral side. (2) Latencies of antidromic spikes of PT cells evoked by stimulation of the medullary pyramidal tract (PYR) had a unimodal distribution with the mean at 4.0 msec. The mean conduction velocity of the pyramidal tract fibers was 10.5 m/sec. (3) Prolonged IPSPs were produced in PT and non-PT cells by single shock stimulation of LH (LH-IPSP). They were significantly longer lasting than those produced by PYR stimulation (PYR-IPSP). (4) The latencies of LH-IPSPs ranged from 1.7 to 25.0 msec and were divided into two groups. The latencies of PYR-IPSPs had a unimodal distribution ranging from 2.5 to 30 msec. (5) In a few non-PT cells, a sequence of brief depolarization and prolonged hyperpolarization occurred in response to LH stimulation. (6) In some non-PT cells, EPSPs which occasionally resulted in spike discharges were observed after LH stimulation. However, no excitation of PT cells was observed by LH stimulation.

Animals↗
PubMed2005

Cutaneous silent periods of the vastus medialis evoked by the stimulation of lateral femoral cutaneous nerve.

OBJECTIVE: Cutaneous silent period (CSP), which is a spinal reflex mediated by A-delta cutaneous afferents, is transient suppression of the electromyographic activity. In this study, our aim is to investigate CSPs of vastus medialis muscle (vm-CSP) evoked by the stimulation of the lateral femoral cutaneous nerve (LFCN) in healthy controls and in patients with meralgia paresthetica (MP). METHODS: Twenty-one patients with MP (17 unilateral, 4 bilateral) and 27 healthy controls were included. Nerve conduction studies of LFCN and vm-CSP were analyzed in all subjects. A stimulus train consisting of five electrical shocks was applied to the skin at the anterolateral side of the thigh for recording of the vm-CSP. RESULTS: Nerve conduction abnormalities of LFCN were observed in all patients with MP. Mean duration of vm-CSP was 69.7+/-9.2ms, and mean onset latency was 44.7+/-6.9 in healthy controls. Onset latency of vm-CSP was significantly prolonged and the duration of vm-CSP was significantly shortened in patients with MP. Vm-CSP abnormalities were observed in 20/25 extremities with MP. CONCLUSIONS: Dysfunction of A-delta afferents may cause these findings in patients with MP. Additionally, spinal modulation of pain may also play a role in the explanation of our findings. SIGNIFICANCE: The present study demonstrates the CSP alterations in the patients with entrapment neuropathy of a cutaneous nerve.

Adult↗
PubMed2001

Distribution and amino acid content of enkephalin-immunoreactive inputs onto juxtacellularly labelled bulbospinal barosensitive neurons in rat rostral ventrolateral medulla.

The activity of bulbospinal (presympathetic) vasomotor neurons of the rostral ventrolateral medulla is modulated pre- and postsynaptically by exogenously applied opioid agonists. To determine whether these neurons receive direct opioid inputs, we examined the relationship between bulbospinal barosensitive neurons and nerve terminals immunoreactive for enkephalin in the rostral ventrolateral medulla of rats. By light microscopy, we mapped the distribution of close appositions by enkephalin-immunoreactive varicosities on 10 bulbospinal barosensitive neurons labelled in vivo with biotinamide. We also examined four labelled neurons ultrastructurally for synapses by enkephalin-immunoreactive terminals and determined with post-embedding immunogold labelling whether these enkephalin-positive terminals contained amino acids. Enkephalin-immunoreactive varicosities closely apposed all bulbospinal barosensitive neurons. Maps of the dendritic distribution of appositions indicated that fast-conducting bulbospinal barosensitive neurons with myelinated axons (conduction velocity >3 m/s; n=3) received many appositions (up to 470/neuron); and slowly conducting neurons with unmyelinated axons (conduction velocity <0.90 m/s; n=3), substantially fewer. Ultrastructural analysis of three fast- and one slowly conducting bulbospinal barosensitive neurons revealed numerous synapses from enkephalin-immunoreactive terminals on cell bodies and dendrites. Enkephalin-positive terminals synapsing on bulbospinal barosensitive neurons contained one or more amino acid: GABA+glycine, glutamate alone or GABA+glutamate. Enkephalin-immunoreactive terminals located near biotinamide-labelled cells contained a similar variety of amino acids. In summary, enkephalin-immunoreactive terminals in the rostral ventrolateral medulla densely innervate lightly myelinated presympathetic neurons and more sparsely those with unmyelinated axons. Enkephalin is present in both excitatory (glutamate-immunoreactive) and inhibitory (GABA- and/or glycine-immunoreactive) terminals. The data suggest that endogenous enkephalin inhibits amino acid release from terminals that innervate bulbospinal barosensitive neurons of the rostral ventrolateral medulla.

Action Potentials↗
PubMed2003

Effects of hydroxyapatite-coated and commercially pure titanium oral implant surfaces on compound nerve action potentials.

The aim of this study was to investigate the effects of hydroxyapatite-coated and commercially pure titanium oral implants on nerve conduction. Isolated rat sciatic nerves were placed between two suction electrodes in a bath containing a tyrode solution. The implants were brought into intimate contact with the nerves and evoked compound action potentials (cAPs) were recorded before and after contact with the implants. The commercially pure titanium implants did not cause any change in cAPs. A gradual reduction in cAPs was observed for hydroxyapatite-coated implants. However, this reduction was < 50% after an application time of 120 min. Recovery of the cAPs in this group was recorded after approximately 60 min. We conclude that, although intimate contact with hydroxyapatite-coated implants leads to a reduction in cAPs in nerves in vitro, neither this surface nor a commercially pure titanium surface leads to irreversible neurotoxic effects.

Action Potentials↗
PubMed1977

Inhibiton of neurons in the amygdala by dorsal raphe stimulation: mediation through a direct serotonergic pathway.

This study presents data showing that the dorsal raphe nucleus (DRN) has a marked inhibitory influence upon neurons in the amygdala and that this inhibitory effect is mediated by a direct DRN-amygdala serotonergic pathway. The evidence may be briefly summarized as follows:(1) on the same amygdaloid cells, both iontophoresis of serotonin (5-HT) and electrical stimulation of the DRN markedly inhibited spontaneous single unit activities; (2) the latency of DRN-induced inhibition was relatively short and is compatible with the conduction velocities (which were determined by antidromic activation of the 5-HT pathway) of unmyelinated 5-HT fibers; (3) destruction of 5-HT projections by 5,7-dihydroxytryptamine (5,7-DHT) or pharmacological depletion of 5-HT by parachlorophenylalanine (PCPA) prevented the inhibitory responsed to DRN stimulation in the great majority of cells studied; (4) in PCPA-pretreated animals, injection of 5-hydroxytryptophan (5-HTP) reversed the PCPA effect, restoring the responses of amygdaloid cells to DRN stimulation. In the amygdala, the presumptive 5-HT antagonists which we tested did not block the inhibitory effects of 5-HT except that intravenously administered LSD blocked the inhibitory responses produced by submaximal DRN stimulation. The implications of these results for the possible functions of 5-HT in the amygdala is discussed.

5-Hydroxytryptophan↗
PubMed2006

Rate coding and spike-time variability in cortical neurons with two types of threshold dynamics.

Neurons and dynamical models of spike generation display two different classes of threshold behavior: type 1 [firing frequency vs. current (f-I) relationship is continuous at threshold] and type 2 (discontinuous f-I). With steady current or conductance stimulation, regular-spiking (RS) pyramidal neurons and fast-spiking (FS) inhibitory interneurons in layer 2/3 of somatosensory cortex exhibit type 1 and type 2 threshold behaviors, respectively. We compared the postsynaptic firing variability of type 1 RS and type 2 FS cells, during naturalistic, fluctuating conductance input. In RS neurons, increasing the level of independently random, shunting inhibition caused a monotonic increase in spike reliability, whereas in FS interneurons, there was an optimum level of shunting inhibition for achieving the most reliable spike generation and the most precise spike-time encoding. This was observed over a range of different degrees of synchrony, or correlation, in the input. RS cells displayed a progressive rise in spike jitter during natural-like transient burst inputs, whereas for FS cells, jitter was mostly kept low. Furthermore, RS cells showed encoding of the input level in the spike shape, whereas FS cells did not. These differences between the two cell types are consistent with a role of RS neurons as rate-coding integrators, and a role of FS neurons as resonators controlling the coherence of synchronous firing.

Action Potentials↗
PubMed1994

Conduction pathways and generators of magnetic evoked spinal cord potentials: a study in monkeys.

Evoked spinal cord potentials (ESCPs) following transcranial magnetic stimulation were recorded from the spinal cord in monkeys anesthetized with ketamine. Isopotential maps of the earlier negative deflection of the magnetic ESCP (N1 wave) revealed a distribution of negative field potentials, the maximum of which were located within the medial dorsolateral funiculus, which corresponds to the dorsolateral corticospinal tracts. The N1 wave of the magnetic ESCP had the same latency as the D-wave of the electrical ESCP elicited by either direct cortical or transcranial electrical stimulation. We assumed that the N1 wave was generated by direct excitation of pyramidal axons. Isopotential maps of the waves that followed the N1 peak (waves N2, N3, N4, and N5) of the magnetic ESCP showed a negative field potential distribution, the maximum of which was at the ventromedial funiculus as well as within the medial dorsolateral funiculus. Later waves of magnetic ESCP were suggested to reflect not only the dorsal corticospinal tracts but also the ventromedial spinal cord function.

Action Potentials↗
PubMed2001

Interhemispheric facilitation of the hand motor area in humans.

1. We investigated interhemispheric interactions between the human hand motor areas using transcranial cortical magnetic and electrical stimulation. 2. A magnetic test stimulus was applied over the motor cortex contralateral to the recorded muscle (test motor cortex), and an electrical or magnetic conditioning stimulus was applied over the ipsilateral hemisphere (conditioning motor cortex). We investigated the effects of the conditioning stimulus on responses to the test stimulus. 3. Two effects were elicited at different interstimulus intervals (ISIs): early facilitation (ISI = 4-5 ms) and late inhibition (ISI > or = 11 ms). 4. The early facilitation was evoked by a magnetic or anodal electrical conditioning stimulus over the motor point in the conditioning hemisphere, which suggests that the conditioning stimulus for early facilitation directly activates corticospinal neurones. 5. The ISIs for early facilitation taken together with the time required for activation of corticospinal neurones by I3-waves in the test hemisphere are compatible with the interhemispheric conduction time through the corpus callosum. Early facilitation was observed in responses to I3-waves, but not in responses to D-waves nor to I1-waves. Based on these results, we conclude that early facilitation is mediated through the corpus callosum. 6. If the magnetic conditioning stimulus induced posteriorly directed currents, or if an anodal electrical conditioning stimulus was applied over a point 2 cm anterior to the motor point, then we observed late inhibition with no early facilitation. 7. Late inhibition was evoked in responses to both I1- and I3-waves, but was not evoked in responses to D-waves. The stronger the conditioning stimulus was, the greater was the amount of inhibition. These results are compatible with surround inhibition at the motor cortex.

Conditioning, Psychological↗
PubMed1987

The structural and functional characteristics of tectospinal neurons in the golden hamster.

Intracellular recording and horseradish peroxidase (HRP) injection techniques were used to delineate the structural and functional characteristics of the superior collicular cells in the hamster, which could be antidromically activated from the first cervical segment of the spinal cord. Thirty-one such neurons were characterized, filled with HRP, and recovered. Complete physiological data were obtained from another 21 tectospinal cells for which anatomical data were sufficient only to define the laminar location of the cell body from which recordings were made. Of the total sample of 52 cells, 7.7% had their somata in the stratum griseum intermediale (SGI), 50% were in the stratum album intermedium (SAI), 36.5% were in the stratum griseum profundum (SGP), and 5.8% were in the stratum album profundum (SAP). The tectospinal cells were fairly uniform morphologically. They had large (27.7 +/- 5.5 microns diameter) cell bodies, which gave rise to an average of 6.7 +/- 1.2 primary dendrites. These were generally smooth and extended up to 500 microns away from the cell body. In many cases, they ascended out of the deep laminae into the stratum opticum (SO) and/or stratum griseum superficiale (SGS). The axons of TS cells averaged 3.4 +/- 0.8 microns in diameter, and they generally coursed radially to the SAP where they curved around the periaqueductal gray and entered the predorsal bundle. These axons often gave rise to collaterals that arborized in the deep laminae of the ipsilateral superior colliculus and subjacent reticular formation. The tectospinal cells were also fairly uniform physiologically. Their average conduction latency was 2.0 +/- 2.3 ms, and this variable had a strong negative correlation (-.81) with axon diameter for the recovered cells. Most (63.5%) of the TS cells were exclusively somatosensory and gave rapidly adapting responses to deflection of vibrissae and/or guard hairs; 7.7% were bimodal (visual-somatosensory); 11.5% had complex (Rhoades et al., '83) somatosensory receptive fields; 1.9% were discharged only by a noxious pinch, and 15.4% were unresponsive. A common feature of all bimodal tectospinal neurons was dendrites that extended at least as far dorsally as the SO. Whereas there were no other clear-cut correlations between the structural and functional characteristics of these tectal neurons, we did note that all of the cells with complex somatosensory receptive fields received inhibitory input from axons that either originated from, or passed through, the contralateral superior colliculus.

Animals↗
PubMed2005

Orderly activation of human motor neurons using electrical ramp prepulses.

OBJECTIVE: Conventional electrical stimulation (rectangular pulses) recruits large before small diameter motor neurons and motor neurons close to the electrode before more distant motor neurons. The present study investigated the possibility for changing the recruitment order of electrical stimuli with sub-threshold ramp prepulses. METHODS: The median nerve was stimulated using surface electrodes at the wrist and elbow. Compound motor action potentials were recorded from abductor pollicis brevis and flexor carpi radialis. Stimulus-response curves, nerve conduction velocity and excitation thresholds of abductor pollicis brevis and flexor carpi radials, with and without ramp prepulses, were recorded in order to study the effect of ramp prepulses on axonal excitability. RESULTS: The conduction velocity of the initial response (10% of the maximal response) was decreased by 4.3+/-0.83m/s with ramp prepulses (500ms, 80% of the excitation threshold). The ramp prepulses also had a differential effect on the excitation thresholds of abductor pollicis brevis and flexor carpi radialis. In addition, ramp prepulses increased the threshold of 10% of the maximal response more than the threshold of 90% of the maximal response. CONCLUSIONS: These results demonstrate that large diameter and motor neurons close to the electrode accommodate more to ramp prepulses than small diameter and distant motor neurons, which suggests that ramp prepulses may be used to change the recruitment order of rectangular pulses. SIGNIFICANCE: This technique of ramp prepulses allows stimulation of alternate subsets of motor nerves.

Adult↗
PubMed1980

[Reactions of neurons of the reticular and ventral anterior thalamic nuclei to electrical stimulation of the centrum medianum of the thalamus].

Responses of 145 reticular (R) and 158 ventral anterior (VA) thalamic neurons to electrical stimulation of centrum medianum (CM) were studied in cats anaesthetized with thiopental sodium (30-40 mg/kg intraperitoneally) and immobilized with d-tubocurarine (1 mg/kg). 4.1% of R and 4.4% of VA neurons under study responded to CM stimulation by antidromic spike (latency 0.3-2.0 ms). The conduction velocity of antidromic excitation in axons of those neurons was found to be 1.7-7.6 m/s. There were neurons which responded by antidromic spike to the other thalamic nuclei stimulation as well as to CM. This fact is the electrophysiological proof of the axonal branching in these neurons. 53.8% of R and 46.9% of VA neurons responded to CM stimulation with orthodromic excitation. Two groups of cells were separated among neurons excited orthodromically. The first group neurons responded to CM stimulation by discharges composed of 6-12 spikes with frequency of 130-640 per second. The neurons of the second group generated a single spike. Inhibitory reactions were noticed only in 0.7% of R and in 4.4% of VA neurons. It is shown that afferent impulses from relay nuclei, lateral posterior nucleus and motor cortex converged to some R and VA neurons responding to CM.

Action Potentials↗
PubMed2002

Recurrent inhibitory dynamics: the role of state-dependent distributions of conduction delay times.

We have formulated and analysed a dynamic model for recurrent inhibition that takes into account the state dependence of the delayed feedback signal (due to the variation in threshold of fibres with their size) and the distribution of these delays (due to the distribution of fibre diameters in the feedback pathway). Using a combination of analytic and numerical tools, we have analysed the behaviour of this model. Depending on the parameter values chosen, as well as the initial preparation of the system, there may be a spectrum of post-synaptic firing dynamics ranging from stable constant values through periodic bursting (limit cycle) behaviour and chaotic firing as well as bistable behaviours. Using detailed parameter estimation for a physiologically motivated example (the CA3-basket cell-mossy fibre system in the hippocampus), we present some of these numerical behaviours. The numerical results corroborate the results of the analytic characterization of the solutions. Namely, for some parameter values the model has a single stable steady state while for the others there is a bistability in which the eventual behaviour depends on the magnitude of stimulation (the initial function).

Animals↗
PubMed1976

Analysis of muscle receptor connections by spike-triggered averaging. 2. Spindle group II afferents.

1. The spike-triggered averaging (STA) method has been used to study synaptic connections of nine spindle group II afferents from medial gastrocnemius to 151 motoneurons of leg muscles in the cat. 2. EPSPs were found in 40 cells, predominantly of triceps surae with latency from cord entry ranging from 0.3 to 4.2 ms. Those with latency less than or equal to 1.4 ms were deduced to be monosynaptic in confirmation of Kirkwood and Sears (13). Mean amplitude for MG-LGS cells was 30.1 muV and mean rise time 1.0 ms (compared with 65.4 muV and 1.0 ms for monosynaptic Ia EPSPs from the preceding report (26)). It is argued that monosynaptic latency for spindle group II afferents could be as large as 1.65 ms. 3. The occurrence of a presynaptic spike permitted the division of EPSP latencies into central conduction time and synaptic delay components. Sindle group II central conduction times were significantly longer than those of Ia afferents, while there were no differences in the synaptic delays associated with the two afferent types. 4. EPSPs of longer latency were judged to be di- or trisynaptic. They were smaller and had longer rise times than the monosynaptic effects. Evidence is presented to show that short rise time of an individual PSP does not guarantee that it is monosynaptic. Rise times are different only on a population basis. 5. Inhibitory responses were found with latencies and mean rise times appropriate for di- and trisynaptic connections. Their mean amplitude was 4.6 muV. 6. The distribution of EPSPs and IPSPs was generally consistent with their exerting stretch reflex effects similar to that of Ia afferents and inconsistent with the inclusion of them in the grouping known as "flexor reflex afferents."

Animals↗
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↗

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