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R Miles

Publications and source records attributed to R Miles.

At least 91 records · Page 5Linked to original sources

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

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

Action Potentials↗

Unitary inhibitory synaptic potentials in the guinea-pig hippocampus in vitro.

Mechanisms involved in the generation of synaptic inhibition have been investigated by making simultaneous intracellular recordings from pairs of neurones in the CA3 pyramidal cell field of guinea-pig hippocampal slices. Inhibitory post-synaptic potentials dependent on single presynaptic action potentials (i.p.s.p.s) and mediated through monosynaptic and disynaptic connexions have been identified. The recurrent nature of some hippocampal inhibition has been demonstrated by showing that activity in a single cell may initiate feed-back i.p.s.p.s onto itself. The observation of synchronous i.p.s.p.s in recordings from two cells illustrates the divergence of synaptic contacts made by inhibitory neurones. The peak conductance change associated with an i.p.s.p. was in the range 5-9 nS and it reversed uniformly throughout its time course at membrane potentials between -73 and -80 mV. The shortest time-to-peak of synaptic potentials was approximately 3 ms and in this case the i.p.s.p. decayed with a time constant comparable to the passive membrane time constant of the post-synaptic neurone. The peak amplitude of i.p.s.p.s fluctuated in a way consistent with the quantal release of inhibitory neurotransmitter. Inhibitory neurones could fire bursts of action potentials not unlike those generated by pyramidal cells in this area. A comparison of the conductance change associated with identified i.p.s.p.s with that associated with the maximal inhibitory post-synaptic potential resulting from electrical stimulation of fibre pathways suggested that, in the slice, a pyramidal cell is innervated by up to fifteen inhibitory neurones.

Action Potentials↗

Local circuit interactions in synchronization of cortical neurones.

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

Animals↗

Does low pH stimulate central chemoreceptors located near the ventral medullary surface?

An in vitro preparation of the medulla oblongata of the rat was used to examine the responses to reducing pH, at constant CO2, of neurons in several identified nuclei. Neurons in an area close to the ventral surface, which is thought to be the location of pH-sensitive central respiratory chemoreceptors, did not respond differently from neurons in other medullary nuclei.

Acid-Base Equilibrium↗

The fontanelle tonometer: a noninvasive method for measurement of intracranial pressure.

The use of a modified pneumotonometer as a noninvasive method to measure intracranial pressure through the fontanel was evaluated in the animal laboratory and in the clinical setting. Pressure measured with the tonometer from a surgically created fontanel in an adult mongrel dog demonstrated good correlation with pressure measured from an epidural balloon catheter. Pressure recorded with the tonometer was compared with direct measurements in a single infant. There were 20 paired measurements with a correlation coefficient of 0.91. Fontanel pressure was measured in 72 healthy infants. The mean pressure was 7.0 mm Hg with a standard deviation of 1.75. This result compares favorably with previous reports utilizing other methods. The machine is safe and simple to use.

Animals↗

Health centre's success story.

The success of Selly Oak's new health centre is apparent from many points of view. Jane Dicks, Richard Miles and Stan Young, all of South Birmingham Health District describe the problems faced and how they were solved to maintain a prodigious building schedule.

Community Health Centers↗

An anaesthetic scavenging system for paediatric and adult use.

A scavening dish is described which removes large volumes of contaminated air. It can be placed close to the open-tailed bag of the paediatric T piece to provide a safe, convenient and efficient scavenger without any modification of the patient circuit. Measurements before and after installation have shown it to be capable of reducing nitrous oxide levels in the operating theatre to between 40 and 0 parts per million. The dish has been incoporated into a scavening system which can also be used with a standard antipollution valve or ventilator exhaust port.

Adult↗

Q fever and animal abortion in Cyprus.

Seventy-eight British soldiers stationed in the Eastern Sovereign Base Area (ESBA) in Cyprus contracted Q fever in the period December 1974 to June 1975. Pneumonia developed in 59% of cases. Of 31 patients tested, 81% had biochemical evidence of hepatitis although only one became clinically jaundiced. Three patients (4%) suffered pericarditis. Treatment with tetracycline had no apparent effect on the course of the disease. Investigation revealed an abortion epidemic involving 21 mixed flocks of sheep and goats in the south-eastern coastal region. 11 of the flocks grazed in and around the ESBA. A serological survey of 10 affected flocks, and evidence collected from previous years, indicated that the abortion epidemic was the result of infection with Coxiella burneti. Infection in the humans was almost certainly acquired by inhalation of dust from brush contaminated with rickettsial parturition products of the aborting flocks. A human serological survey revealed a number of cases of subclinical Q fever in a susceptivle military population, and an asymptomatic epidemic in a largely immune local position.

Abortion, Veterinary↗

[Long-term depression of excitatory synapses in the cortex and hippocampus].

The efficacy of excitatory synapses terminating on cortical and hippocampal pyramidal cells may be persistently depressed as well as potentiated. Homo-synaptic long-term depression (LTD) seems to be triggered by an entry of calcium into a post-synaptic cell less than that needed to initiate long-term potentiation (LTP). Theoretical work predicted, and experimental studies confirmed, that moderate elevations of calcium initiate LTD via a cascade of biochemical interactions involving calcium-dependent phosphatases. Genetically modified animals confirmed the prediction of a sliding threshold that defines the limit between LTD and LTP. While mechanisms for the initiation of LTD are quite well established, it remains unclear whether pre- or post-synaptic mechanisms, or both, are involved in its maintenance. A role for LTD in processes of learning and forgetting in the adult animal remains to be firmly established. It seems probable, however, that a persistent reduction in synaptic weight is a basic process used in the establishment and refinement of neuronal circuits during development.

Animals↗

Single neurones can initiate synchronized population discharge in the hippocampus.

The synchronized firing of neuronal populations is frequently observed in the mammalian central nervous system. The generation of motor activities such as locomotion and respiration requires the simultaneous activation of many neurones and synchronous firing also underlies the cortical alpha rhythm and the hippocampal theta rhythm. However the influence that single neurones may have on such neuronal population discharges is not clear. We have examined this question using small isolated segments of the CA3 region of the guinea pig hippocampus. We report here that in the presence of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, these segments spontaneously generate synchronized rhythmic bursts comparable with the interictal epileptiform discharges observed in the hippocampus and neocortex in the presence of penicillin. The activation of some individual neurones by intracellular current injection can partially entrain and reset the rhythm. The probability that a synchronized burst will follow stimulation of a single cell increases with time after a spontaneous synchronized discharge, suggesting that each population discharge is followed by a period of relative population refractoriness. A delay of 40-200 ms elapses between the activation of a single neurone and the synchronized discharge. We suggest that during this time activity elicited in one neurone spreads to other neurones through multisynaptic excitatory pathways and leads eventually to the participation of the whole population in a synchronous burst.

Animals↗

Latent synaptic pathways revealed after tetanic stimulation in the hippocampus.

Synaptic plasticity may result from changes at existing synapses or from alterations in the number of functional synaptic connections. In the hippocampus excitatory synaptic strength is persistently enhanced after tetanic stimulation. Here we report that latent synaptic pathways may also become functional. Simultaneous intracellular recordings were made from pairs of CA3 pyramidal cells in slices from guinea pig hippocampus. After stimulating afferent fibres repetitively, polysynaptic excitatory pathways between previously unconnected cells became apparent. The efficacy of recurrent inhibitory circuits was also reduced. The loss of inhibitory control is of interest because latent excitatory pathways are revealed after pharmacological suppression of inhibition. This plasticity in local synaptic circuits leads to the emergence of synchronous firing in groups of CA3 cells. The formation of groups of associated cells and the ability of some cells to initiate synchronous firing in a larger cell group through recurrent pathways is reminiscent of several models of information storage and recall in the cortex.

Animals↗