Search PubMed⌕ Search

Biomedical subjects

R Miles

Publications and source records attributed to R Miles.

At least 73 records · Page 4Linked to original sources
PubMed1990

Racism, migration and the state in Western Europe: a case for comparative analysis.

This paper offers a framework for the comparative analysis of international migration into Western Europe since 1945. It identifies "the migration of four analytically distinct categories of person which highlights the role of the state in the reproduction of the imagined community of nations. That role is carried out in the context of a more general process of the regulation of scarcity, in the course of which people are simultaneously included in and excluded from the hierarcy of economic, political and ideological positions in the nation-state. Of special interest is the content of the processes of signification and categorisation that are generated in the inclusionary and exclusionary processes. The countries selected for analysis are France, the Netherlands and Britain."

Acculturation↗
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↗
PubMed1989

The grafted hippocampus: an epileptic focus.

Field potentials and unitary activity were investigated in the grafted and the host hippocampi in freely moving rats and in vitro. The subcortical afferents and efferents of the hippocampus (fimbria-fornix, FF) were removed by aspiration. Solid pieces of hippocampal grafts derived from 15- to 16-day-old fetuses were placed in the lesion cavity in rats with unilateral FF lesions, and cell suspensions prepared from fetal hippocampi were grafted directly into the host hippocampi in animals with bilateral FF lesions. Reciprocal communication between the grafted and the host hippocampi was monitored with a 16-microelectrode probe from 7 to 10 months after grafting. The fluorescent retrograde tracer, Fluorogold, was used to examine graft-host projections and acetylcholinesterase staining to reveal host-derived fibers in the graft. The most typical neuronal pattern of the hippocampal graft was a highly synchronous population burst with concurrent EEG spike. The speed of propagation of the EEG spike within the graft and across the graft-host interface was either fast (greater than 3 m/s) or slow (less than 0.5 m/s). Large amplitude, short duration EEG spikes usually propagated with a high speed, while smaller amplitude, wider spikes with broad population bursts spread at a lower velocity. The direction of propagation was usually uniform indicating that the population burst was triggered by a localized subgroup of highly excitable neurons ("focus"). Spontaneous seizures were also present in the solid graft which frequently invaded the host hippocampus. The incidence of EEG spikes was three times higher in rats with bilateral suspension grafts than in animals with FF lesion only. In about half of the grafted rats spontaneous behavioral seizures were also observed. Intracellular recordings from putative pyramidal cells in the graft and in the host revealed large amplitude (10-12 mV), spontaneously occurring EPSPs. IPSPs were difficult to detect even during depolarizations of up to 20 mV from rest. We suggest that the increased excitability of the hippocampal graft is due to the high incidence of recurrent excitatory collaterals terminating on or close to the somata of pyramidal neurons. Population bursts may spread fast via extensively arborizing axon collaterals or slowly by successively activating new sets of neighboring neurons. Spontaneous behavioral convulsions are explained by assuming that the grafted hippocampus serves as an epileptic focus which is capable of kindling the host brain by repeated seizure induction.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
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

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↗
PubMed1987

Inhibitory control of local excitatory circuits in the guinea-pig hippocampus.

1. Exposure to the gamma-aminobutyric acid antagonist, picrotoxin, causes the discharge of hippocampal pyramidal cells to become synchronized. Synaptic mechanisms underlying the development of synchrony were investigated by recording from pairs of cells in the CA3 region of guinea-pig hippocampal slices. 2. Picrotoxin suppressed unitary inhibitory synaptic events. It appeared not to affect monosynaptic excitatory connections. Picrotoxin revealed latent excitatory connections in seven out of twenty-one dual recordings from burst-firing cells. 3. Post-synaptic events revealed by picrotoxin were elicited rarely by single action potentials. They were evoked with mean latencies of at least 8 ms and with more than 30% failures of transmission by bursts of three or more action potentials. They were suppressed by increasing extracellular Ca2+. They were considered to be mediated by polysynaptic excitatory pathways. 4. Polysynaptic excitatory post-synaptic potentials (e.p.s.p.s) had a smooth rising phase with time-to-peak of 15-40 ms and a falling phase of similar duration. Their amplitude was 2-3 mV at membrane potentials close to -70 mV. This shape was similar to that of summed e.p.s.p.s evoked by a burst of three to six action potentials at monosynaptic connections between CA3 cells. 5. One cell could evoke excitatory synaptic events in more than one follower cell, suggesting that axon collaterals mediating recurrent excitation were divergent. More than one polysynaptic excitatory pathway could exist between two cells. 6. We examined the role of recurrent excitatory synapses in the development of synchrony. As inhibition was suppressed by picrotoxin, simultaneous excitatory synaptic events appeared in recordings from pairs of cells. They occurred rhythmically at intervals of 0.5-3 s and grew in amplitude with time. Synchronous neuronal discharges were observed when the threshold for action potential generation was exceeded. 7. Firing induced in one cell could sometimes evoke a sequence of post-synaptic events in another cell as inhibition was suppressed. Initially, no connection was detected. On adding picrotoxin, a polysynaptic e.p.s.p. was revealed and with time longer-latency components were recruited to the synaptic event. The amplitude of later components grew until firing threshold was reached. 8. We suggest that synchronous firing develops due to the loss of inhibitory control over the spread of firing between CA3 pyramidal cells via divergent, polysynaptic, recurrent excitatory pathways.

Action Potentials↗
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

Unmasking AIDS: chemical immunosuppression and seronegative syphilis.

In both African AIDS populations and homosexual populations outside of Africa, a high incidence of syphilis and multiple exposures to infectious diseases results in frequent, often abusive use of antibiotics. Epidemiological evidence exists for chemical immunosuppression resulting from antibiotics and other prescribed and recreational drugs prior to the current AIDS crisis. Analysis and review of literature is given on the effects of subcurative doses of antibiotics masking and distorting the expression of secondary and tertiary syphilis. A high incidence of seronegative syphilis is found in Africa and compares with Western reports of seronegativity and persistence of treponemes despite adequate antibiotic therapies. Late latent and tertiary syphilis produce symptoms and immunosuppression comparable to that seen in the current AIDS crisis. Screening procedures instituted for a group of gay men with AIDS and AIDS related conditions is revealing evidence of chemically immunosuppressed syphilis as a factor in AIDS. Key words: AIDS, immunosuppression, syphilis, chemical immunosuppression, seronegativity, immunosuppressive sera, etiology of AIDS.

AIDS-Related Complex↗
PubMed1986

Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus.

Excitatory synaptic interactions between CA3 neurones in slices from guinea-pig hippocampus were examined. Recurrent excitatory post-synaptic potentials (e.p.s.p.s) were evoked by action potentials in a single presynaptic neurone or by the antidromic activation of part of the CA3 pyramidal cell population. The peak amplitude of unitary e.p.s.p.s was 1-2 mV at potentials between -64 and -70 mV. Their time to peak was 7-12 ms and the initial phase of their decay was slower than that of a somatically injected voltage pulse. Recurrent e.p.s.p.s were often followed by a small (0.3 mV) hyperpolarization, or undershoot. Recurrent e.p.s.p.s were compared with e.p.s.p.s evoked by stimulating mossy fibres, which terminate proximally on apical dendrites of CA3 pyramidal cells. They were of slower time course and reversed at a more positive potential than mossy fibre e.p.s.p.s. Some synaptic terminals made by recurrent axon collaterals apparently terminate at distant locations on apical dendrites. The decay of both recurrent e.p.s.p.s and dendritic voltage pulses was prolonged by membrane depolarization within a 10-15 mV subthreshold potential range. Voltage-dependent inward currents activated by the synaptic depolarization may contribute to the slow initial decay of these synaptic events. The undershoot did not occur when transmission of a unitary e.p.s.p. failed and was of slower time course than the hyperpolarization due to an inhibitory post-synaptic potential (i.p.s.p.). It was suppressed by intracellular application of K+ channel blockers and probably reflects an intrinsic outward current activated as a consequence of the synaptic depolarization. Considerable temporal summation of synaptic potentials occurred when recurrent synapses were activated twice at an interval of 5-10 ms, typical of the spontaneous burst firing pattern of CA3 neurones. The mean facilitation of a second e.p.s.p. at this interval was about 0.6. The efficacy of a third and subsequent e.p.s.p.s at similar interval was reduced. Presynaptic bursts of three to five action potentials evoked summed e.p.s.p.s of amplitude 2-4 mV, with time to peak 20-40 ms and decaying phase of similar duration. Their rising phase was relatively smooth and summed events were succeeded by an undershoot. Presynaptic bursts could cause a post-synaptic neurone to discharge.

Action Potentials↗
PubMed1986

Frequency dependence of synaptic transmission in nucleus of the solitary tract in vitro.

Afferent fibers from visceral sensory receptors enter the medulla oblongata, form the solitary tract, and synapse with neurons in the nucleus of the solitary tract. In the present study longitudinal slices were prepared from guinea pig medulla in order to examine the properties of transmission at these synapses in vitro. Synaptic responses to selective stimulation of solitary tract fibers were recorded intracellularly from neurons in an area, close to the obex and immediately medial and lateral to the tract, where arterial baroreceptor fibers are known to terminate. The amplitude of maximally evoked postsynaptic potentials (PSPs) in solitary tract neurons was strongly dependent on stimulus frequency. On increasing frequency from 0.5 to 20 Hz, a PSP depression of 80% was reached in 4-8 s. The mean depression was 35% at 5 Hz and 60% at 10 Hz. Sufficient local connections were retained in vitro that solitary tract stimulation evoked disynaptic inhibitory potentials and long latency, possibly polysynaptic, excitatory potentials in some neurons. The possibility that frequency-dependent changes in the efficacy of these local synaptic circuits contributed to PSP depression was examined. The role of postsynaptic inhibition in synaptic depression was tested by examining the frequency dependence of PSPs at membrane potentials close to the reversal of their excitatory component. The resulting hyperpolarizing PSPs were also depressed suggesting that a facilitation of postsynaptic inhibition at high frequency does not underlie the depression. The contribution of depression in multisynaptic excitatory pathways to PSP depression was assessed by exclusion. At low stimulus intensities, excitatory synaptic events with no long latency components were evoked. These events exhibited a similar frequency dependence to that of maximal PSPs. These results suggest that mechanisms operating at synapses made by solitary tract fibers are responsible for the frequency dependence of PSPs recorded in solitary tract neurons. Such mechanisms might contribute to the adaptation of some cardiovascular reflexes initiated by baroreceptors.

Animals↗
PubMed1986

Intracellular fluoride alters the kinetic properties of calcium currents facilitating the investigation of synaptic events in hippocampal neurons.

We have attempted to suppress voltage-dependent conductances in hippocampal neurons by introducing various intracellular agents. Voltage-clamp studies were carried out using acutely dissociated hippocampal neurons from adult guinea pigs. Synaptic events were examined using intracellular recordings in the slice preparation. Sodium conductance was suppressed when the quaternary lidocaine derivative QX 314 was introduced intracellularly. Potassium conductances were blocked by intracellular cesium or Tris. We also found that the anion fluoride could affect calcium conductance by an intracellular action. When anions other than fluoride were used for intracellular recordings, the voltage-dependent calcium current inactivated slowly and showed persistent activation at membrane potentials between -40 and -10 mV. In contrast, when fluoride was present intracellularly, the inactivation kinetics of the calcium current were accelerated and the persistent component of the current was largely suppressed. Intracellular recordings in the hippocampal slice showed that when electrodes contained cesium, QX 314, and fluoride, the spiking and nonlinear responses of the neuronal membrane to depolarization were blocked. In these conditions the time course and voltage-dependence of EPSPs could be examined in detail without complications due to voltage-dependent currents of the postsynaptic cell.

Animals↗
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

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↗