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E Maru

Publications and source records attributed to E Maru.

14 recordsLinked to original sources

Time discrete model of recurrent inhibition in hippocampal dentate gyrus.

A time discrete model of recurrent inhibition in the hippocampal dentate gyrus is made and analyzed. This model assumes that (1) each granule cell can generate only one action potential in response to a single stimulation of the perforant path, (2) each interneuron receives synaptic inputs from many granule cells, and (3) an output of the interneuron is inhibitory for granule cells. Although each granule cell generates an action potential in the all-or-none fashion, the population spike is shown to be approximated by a piecewise linear function of the population excitatory post-synaptic potential (EPSP). From this model six patterns in the population spike responses to the paired-pulse stimulation are deduced. Each pattern is composed of some broken lines whose slopes and intercepts are explicitly expressed by the average and variance of the microscopic parameters and the population size of the cells. This model clarifies the relation between the measured quantity in the field potential experiment and the microscopic quantities peculiar to the granule cell and to the interneuron.

Action Potentials

Is synaptic potentiation necessary for the development of kindling?

Field potentials were recorded from the dentate gyrus of freely moving rats to examine the role of synaptic potentiation in the development of seizure susceptibility during rapid kindling. Kindling stimulations (10 Hz for 10 sec) were delivered to the perforant path at every 5 min for 5 or 6 hrs. This procedure produced a sustained depression of excitatory synaptic transmission at the perforant path-granule cell synapse during and after kindling. However, the kindling procedure resulted in the prolongation of afterdischarges and the development of interictal discharges originated from granule cells, indicating an increase in the seizure susceptibility of these neurons. These results indicate that synaptic potentiation is not a critical requirement for an increase in seizure susceptibility during rapid kindling, even if it has a facilitating effect on the development of kindling as suggested in previous studies.

Animals

[Effects of pentobarbital on hippocampal dentate field potentials in unrestrained rats].

The field potential technique was used to examine the effects of pentobarbital (40 mg.kg-1, ip) on the excitatory synaptic transmission and synchronous discharge of granule cells in the hippocampal dentate area of unrestrained rats. Two components of the dentate field potential evoked by perforant path stimulation were analyzed; the population EPSP and the population spike representing an extracellular excitatory postsynaptic potential and synchronous discharge, respectively. The rate of rise (slope) of the population EPSP decreased within 5 min after an injection of pentobarbital. This depression of excitatory synaptic transmission lasted for about 2 hrs and then recovered to near the pre-drug control level within 3 hrs. The ratio of population spike amplitude to population EPSP slope (S/E ratio) was calculated to estimate the readiness of granule cells for synchronous discharge. After an injection of pentobarbital the S/E ratio increased for 2 hrs, indicating that the synchronous discharge of granule cells was facilitated by the drug in spite of the depression of excitatory synaptic transmission. Under pentobarbital anesthesia, the onset and peak latencies of population spikes were prolonged for 0.2-0.4 msec.

Animals

Effects of LTP-inducing tetanic stimulations of the perforant path on the commissural inhibition and facilitation of dentate granule cell discharge.

Effects of diazepam (1 mg/kg, i.p.) on the commissural influences on granule cells were first examined to further assess its GABAergic inhibitory mechanism. Whereas the commissural inhibition at an interval of 5-8 ms of the contralateral dentate-perforant path (CP) combined stimulus was not enhanced by diazepam, the commissural facilitation at a CP interval of 11-20 ms was reduced, suggesting that the GABAergic inhibition is involved in rather a part of the commissural facilitation at a CP interval of 11-20 msec than a part of the 'commissural' inhibition at a shorter CP interval. Based on the results of diazepam, effects of high-frequency stimulations of the perforant path on the commissural inhibition of dentate granule cells were then examined, in relation to their effects on the dentate paired-pulse depression. These stimulations produced the long-term potentiation of the perforant path-dentate excitatory synapse and significant reduction of the paired-pulse depression. The commissural inhibition at a CP interval of 5-8 ms remained unchanged following tetanization. The commissural facilitation at a CP interval of 11-20 ms was, however, slightly enhanced by tetanic stimulations and a statistical significance was obtained at a CP interval of 19 ms. These results imply that tetanic stimulations of the perforant path selectively reduce the GABAergic component of the commissural inhibition, as well as that of the paired-pulse depression.

Action Potentials

Long-lasting reduction of dentate paired-pulse depression following LTP-inducing tetanic stimulations of perforant path.

Effects of high-frequency stimulations of the perforant path on the dentate paired-pulse depression were examined in urethane-anesthetized rats. The tetanic stimulations produced a long-term potentiation (LTP) of the excitatory synaptic transmission at the perforant path-dentate granule cell synapses in almost all animals examined. The strength of the early paired-pulse depression at an inter-pulse interval (IPI) of 20 ms decreased significantly for at least 60 min after the tetanic stimulations, whereas the late paired-pulse depression at an IPI of 2 s remained almost unchanged. The reduction of the early paired-pulse depression was stepwise augmented by each of successive tetanic stimulations given at an interval of 10 min. A preceding antidromic stimulation of the mossy fibers depressed the population spike amplitude of perforant path response at an interval of 5-9 ms. The strength of the antidromic depression of population spike also decreased following the perforant path tetanic stimulations. These results suggest that tetanic stimulations of the perforant path produce a long-lasting reduction of the GABAergic recurrent inhibition in the dentate area associated with LTP. The possible mechanisms of the decrease in GABAergic inhibition produced by tetanic stimulations and its possible effects on the development of LTP with succeeding tetanic stimulations were discussed.

Action Potentials

Microcomputer-controlled laboratory system for field potential experiments.

A microcomputer-controlled laboratory system for hippocampal field potential experiments was constituted. This system realized the quasi-simultaneous processing of execution of stimulation, data acquisition, data display and data analysis by means of a microcomputer for the first time. To attain this quasi-simultaneous processing, a new algorithm for drawing a tangent on the wave-form of the potential was contrived, which enabled rapid analysis of an arbitrary population spike even in the case of generation of double spikes. The system has the following functions: (1) execution of the programmed stimulation paradigm, (2) analog/digital (A/D) conversion of the evoked field potential with a sampling interval of more than 50 microseconds per channel, (3) display of the A/D converted wave-form data on a CRT and storage of the data on a floppy disk, (4) on-line analysis of the population excitatory postsynaptic potential (EPSP) and population spike, (5) more detailed off-line analysis of the field potentials, and (6) output of the wave-form data and measured values through a printer and an X-Y plotter.

Action Potentials

Alteration in dentate neuronal activities associated with perforant path kindling. I. Long-term potentiation of excitatory synaptic transmission.

One candidate for the neuronal mechanism of kindling is the facilitation of excitatory synaptic transmission. The population EPSP component of the perforant path-dentate field potential is strongly potentiated by the first few kindling stimulations applied to the perforant path. As kindling proceeds further, however, subsequent changes in transmission efficacy have been a source of controversy. The present study reexamines these changes in transmission efficacy of the perforant path-dentate granule cell synapses during and after perforant path kindling using improved methods of analysis of the field potentials recorded in freely moving rats. The slope of the regression line of the population EPSPs on a range of stimulus strength values was found to be enhanced by the first kindling stimulation and then continued to increase gradually with subsequent kindling stimulations, indicating a cumulative increase in synaptic transmission efficacy throughout the period of kindling. The potentiated excitatory synaptic transmission lasted for at least 1 month after the cessation of kindling. On the other hand, the kindling stimulations produced a progressive increase in the x-intercept of the regression line, indicating an increase in the minimal EPSP threshold. These two effects seem to account for the apparent discrepancy between previous studies, each of which measured the population EPSP at a fixed stimulus strength.

Animals

Alteration in dentate neuronal activities associated with perforant path kindling. II. Decrease in granule cell excitability.

Changes in the excitability of the dentate granule cells after perforant path kindling were examined by the analysis of perforant path-dentate gyrus field potentials recorded in freely moving rats. Using a range of test pulse intensities, the population spike heights (cellular output) were plotted against the magnitudes of the associated population EPSPs (synaptic input), and a linear regression (input/output) was estimated from the relative linear portion of the plot. The x-intercept of this regression defines the population spike threshold. With kindling, the overall amplitude of the population spikes decreased, in spite of an increase in the population EPSPs resulting in a flatter input/output regression. The x-intercept of the regression was unaffected by the first kindling stimulation, but consistently and significantly increased with subsequent kindling. These changes gradually reverted to near the prekindling control values during a postkindling rest period of 1 month, and were reinstated by rekindling after the period of rest. Similarly, the onset and peak latencies of the population spike were significantly retarded during the period of kindling. These results suggest that seizure activity causes a significant but temporary reduction in the excitability of dentate granule cells. This effect would tend to counteract the process of kindling and provide an explanation for some of the phenomena of postictal depression.

Animals

Alteration in dentate neuronal activities associated with perforant path kindling. III. Enhancement of synaptic inhibition.

Changes in the hippocampal commissural inhibition of dentate granule cell firing following perforant path kindling were examined by analysis of field potentials recorded in freely moving rats. Prior stimulation of the contralateral dentate hilus inhibits the dentate population spike response to perforant path stimulation at interpulse intervals of less than 11 ms via GABAergic control. This measure of inhibition was gradually enhanced from 26.6% to 76.9% by kindling stimulations delivered to the perforant path once a day for 3 weeks. It then decreased from 76.9% to 54.6% within 2 weeks after the last kindling trial, and remained at approximately this value for another 18 days of observation. Similarly, the mean maximum duration of commissural inhibition significantly increased from 7.43 ms to 10.6 ms during the kindling period, and decreased to 8.29 ms 2 weeks later. These results indicate that perforant path kindling temporarily increased the synaptic inhibition of granule cells, in a close temporal relationship to the temporary decrease in the granule cell excitability observed in our preceding study.

Animals

Effects of median raphe nucleus lesions on hippocampal EEG in the freely moving rat.

The effects of median raphe lesions on the hippocampal EEG were examined in freely moving rats. First, median raphe lesions, including those restricted to the median raphe nucleus, unequivocally produced hippocampal low-frequency theta activity (5.8 Hz, SD = 0.47 Hz) during relaxed immobility which was not observed under normal conditions. This lesion-induced theta activity during immobiliy continued for at least 20 days, and was markedly suppressed by atropine sulfate (10 mg/kg, i.p.). On the other hand, reticular formation lesions had little effect on either hippocampal EEG patterns during immobility, movement or PS. Second, the mean frequency of theta activity was significantly reduced during movement and PS on the day following the median raphe lesion. These findings suggest a raphe-hippocampal pathway in which the median raphe mucleus plays a major role in hippocampal desynchronization (irregular pattern) by exerting an inhibitory influence on the hippocompal theta generating or facilitating mechanism. Thus the theta activity will be induced by the disinhibition following median raphe lesions.

Animals