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Behavior-dependent paired-pulse responses in the hippocampal CA1 region.

Paired-pulses of 20-100 ms interpulse interval (IPI) were delivered to the Schaffer collaterals/commissural fibers in order to excite the apical dendrites of the hippocampal CA1 region in freely behaving rats. Significant differences were observed for the paired-pulse responses during different behavioral states. The responses recorded during awake immobility (IMM), and slow-wave sleep (SWS) were similar, but as a group, were different from those during walking (WLK) and rapid-eye-movement sleep (REM). During WLK and REM, the population spike evoked by the second pulse (P2) at IPI of 30 and 50 ms, was greatly facilitated as compared to the population spike evoked by the first pulse (P1), i.e. P2 greater than P1. During IMM and SWS and using moderate stimulus intensities, P2 was generally smaller than P1 (paired-pulse suppression) at IPI of 30 and 50 ms. The P2/P1 relation with behavior was not caused by the slight variations of P1 with behavior. In addition, paired-pulse facilitation of the population excitatory postsynaptic potentials (EPSP) was relatively small and not significantly dependent on behavior. Behavioral dependence of the paired-pulse responses was not generally found for IPI of 20 or 100 ms. It is concluded that paired-pulse facilitation at 30-50 ms IPI can best be explained by EPSP facilitation combined with a behaviorally dependent disinhibition.

Animals↗

Adenosine, L-AP4, and baclofen modulation of paired-pulse potentiation in the dentate gyrus: interstimulus interval-dependent pharmacology.

Paired-pulse potentiation of the glutamate-mediated excitatory postsynaptic potential (EPSP) recorded in the dentate gyrus molecular layer is thought to be mediated presynaptically. It is known that the activation of adenosine (A1) and GABAB receptors results in the reduction of glutamate release in the dentate molecular layer via presynaptic mechanisms. To examine possible modulatory roles of these receptors on paired-pulse potentiation, we examined the effects of adenosine and baclofen (a GABAB agonist) on paired-pulse potentiation using extracellular recording from the lateral perforant path in rat hippocampal slices maintained in vitro. We compared these effects with those of L-alpha-amino-4-phosphonobutyric acid (L-AP4) over a wide range of interstimulus intervals (ISIs). L-AP4 enhanced paired-pulse potentiation over the full range of ISIs tested (40-800 ms), whereas adenosine enhanced paired-pulse potentiation only at ISIs of 40-100 ms. In contrast, baclofen reduced paired-pulse potentiation only at ISIs of 400-800 ms. Furthermore, baclofen increased the amplitude of lateral perforant path field potentials, previously reported to be baclofen-insensitive. These results suggest that paired-pulse potentiation can be modulated through the activation of adenosine and baclofen receptors, indicate that this modulation is dependent on ISI, and show that there are at least two pharmacologically separable components of paired-pulse potentiation in the dentate gyrus.

Adenosine↗

Slow inward and late slow outward currents induced by hyperpolarizing pre-pulses in cat bladder parasympathetic neurones.

Single-electrode voltage-clamp techniques were used to examine membrane currents recorded as a result of hyperpolarizing pre-pulses in cat bladder parasympathetic neurones. In 84 ganglion cells examined, two types of current were observed in response to hyperpolarizing pre-pulses of 10 ms to 1 s duration from holding potentials of -30 to -60 mV to test potentials of -90 to -130 mV. In 46 cells, a short-duration pulse induced a slow inward current (SIC); with longer pulse durations, an outward current was superimposed on the SIC, resulting in a late slow outward current (LSOC). In the remaining cells, either a SIC (n = 12) or an LSOC (n = 26) was recorded over a range of hyperpolarizing pre-pulse durations. The more depolarized the holding potential, the more hyperpolarized the test potential and the longer the pulse duration, the larger the amplitude of the SIC and LSOC. The SIC and LSOC were associated with an increase in input conductance. The extrapolated reversal potential (Vrev) for the LSOC obtained at a holding potential of -60 mV (where the LSOC seemed to be less contaminated with the SIC) was -89 +/- 4 mV (mean +/- standard error of the mean; n = 5), which is close to the equilibrium potential for the K ion. The LSOC was depressed by a high-K (10-20 mM) solution and potentiated by a low-K (0.47 mM) solution. The SIC was depressed by a low-Na (26.2 mM) solution, but was not affected significantly by a low-Cl (12.2 mM) solution. A low-Ca (0.1 mM)/high-Mg (5 mM) solution depressed the LSOC, while a high-Ca (5 mM) solution potentiated it. Cd (0.5 mM) blocked the SIC almost completely, and suppressed the LSOC. The LSOC but not the SIC was suppressed by tetraethylammonium chloride (10 mM). Superfusing Cs (3 mM) did not affect either the LSOC or the SIC. 4-Aminopyridine (1 mM) and muscarine (10 microM) depressed or replaced the SIC with an outward current, while potentiating the LSOC. These results suggest that a hyperpolarizing pre-pulse induces slow inward Na- and late slow outward Ca-dependent K currents, which are inactivated at depolarized potentials and are de-inactivated by hyperpolarizing pulses in a time-dependent manner.

4-Aminopyridine↗

Time course of O2-pulse during various tests of aerobic power.

The purpose of this study was to test the hypothesis that oxygen pulse typically reaches a maximum before maximal oxygen consumption by observing the time course of oxygen pulse throughout exercise to maximal stress and to discern those physiologic variables which might predispose an individual to reach a peak in oxygen pulse before achieving maximal oxygen consumption. Thirty male volunteers ranging in age from 18-25 (X = 20.5) years were recruited for this study. Maximal oxygen uptake was assessed on both bicycle ergometer and treadmill. Based upon the results of the exercise tests, subjects were classified into subgroups as a consequence of whether or not a maximal oxygen pulse or a plateau in oxygen pulse was demonstrated during submaximal exercise. The results indicate that submaximal peaking or at least the achieving of plateau values of oxygen pulse does in fact occur in some but not all indivuals. It was observed that this phenomenon occurs at a relatively high percentage of maximal heart rate and maximal oxygen consumption. It appeared that individuals who demonstrate low heart rates at low-work intensities, high maximal heart rates, and a disproportionate increase in R for a given ventilation are most likely to reach a submaximal peak in oxygen pulse. Oxygen pulse during submaximal exercise appears to provide a good indication of cardiorespiratory fitness.

Adolescent↗

Running activity mediates the phase-advancing effects of dark pulses on hamster circadian rhythms.

Pulses of darkness can phase-shift the circadian activity rhythms of hamsters, Mesocricetus auratus, kept in constant light. Dark pulses under these conditions alter photic input to the circadian system, but they also commonly trigger wheel-running activity. This paper investigates the contribution of running activity to the phase-shifting effects of dark pulses. A first experiment showed that running activity by itself can phase-shift rhythms in constant light. Hamsters were induced to run by being confined to a novel wheel for 3-5 h. When this was done at circadian times (CT) 0, 6, and 9, the mean steady-state phase-shifts were 0.6 h, 3.5 h, and 2.3 h, respectively. The latter two values are at least as large as those previously obtained with dark pulses of similar durations and circadian phases. A second experiment showed that restricting the activity of hamsters during 3-h dark pulses at CT 9 reduces the amplitude of the phase-shifts. Unrestrained animals phase-advanced by 1.1 h, but this shift was halved in animals whose wheel was locked, and completely abolished in animals confined to nest boxes during the dark pulse. Activity restriction in itself (without dark pulses) had only minimal phase-delaying effects on free-running rhythms when given between ca. CT 10 and CT 13. These results support the idea that, in hamsters at least, dark pulses affect the circadian system mostly by altering behavioural states rather than by altering photic input to the internal clock.

Animals↗

Hyperopia correction by noncontact holmium: YAG laser thermal keratoplasty: five-pulse treatments with 1-year follow-up.

BACKGROUND: Previous noncontact holmium (Ho): YAG laser thermal keratoplasty (LTK) studies on correction of low to moderate hyperopia have used treatment algorithms based on ten-pulse, variable-pulse-energy treatment parameters. The purpose of this study was to evaluate the safety, effectiveness, and stability of new five-pulse, constant-pulse-energy treatment parameters for noncontact Ho:YAG LTK. METHODS: Thirty-nine hyperopic patient eyes [up to +4.75 diopters (D) refractive error] were treated using simultaneous noncontact delivery of Ho:YAG laser energy (Sunrise) with two symmetrical octagonal rings of eight spots per ring and radial spot patterns on centerline diameters of 5 and 6 mm (group A), 6 and 7 mm (group B), or 6.5 and 7.5 mm (group C). Each ring of spots received five pulses of laser light at 5 Hz pulse repetition frequency and a fixed pulse energy of 240 mJ. Thirty of the 39 patient eyes (77%) had 1-year follow-up exams. RESULTS: At 1 year, the mean Snellen uncorrected distance visual acuity lines gained was 3.7 +/- 0.5/6.8 +/- 2.7/5.3 +/- 3.3 for groups A, B, and C. The mean changes in subjective manifest refraction (spherical equivalent) were -2.08 +/- 1.13 D, -1.83 +/- 0.88 D, -1.22 +/- 0.88 D for groups A, B, and C respectively. None of the eyes lost two or more lines of spectacle-corrected distance visual acuity. There were no clinically significant complications in any patient. CONCLUSION: This clinical study indicates that five-pulse noncontact LTK treatments of low hyperopia are safe and effective. The stability has to be confirmed with longer follow-up.

Adult↗

The Stealth Station Image Guidance System may interfere with pulse oximetry.

PURPOSE: Interference on pulse oximetry can come from many sources. We found an additional source of interference from the Stealth Station. This article gives an overview of sources of pulse oximeter interference so that clinicians can better prevent them. Technical features: This article discusses the infrared disturbances caused by the Stealth Station. The Stealth Station is a frameless stereotactic positioning system that utilizes a three dimensional location system to measure the position of the patient and the surgical tools, and to relate those positions to previously recorded imaging. To understand the disturbance caused by the Stealth Station, we discuss its operation and that of pulse oximeter monitors. Pulse oximeter interference can come from volume artifacts, electrical and light noise, and can be caused by issues related to the patient. Because the passive Stealth Station contains a strong infrared light source, interference caused by light is a likely reason for the interference we noted. Pulse oximeters rely on the time-variant light signal modulated by arterial volume variations in the finger. Although relatively immune to static light sources, pulse oximeters are extremely sensitive to time-varying light sources. The light emitted by the passive Stealth Station is time-varying at 4 Hz and this is causing the pulse oximeter to provide invalid results. Shielding can generally be used to stop the light from the Stealth Station from being picked up by the pulse oximeter sensor. CONCLUSION: Infrared light interference can be very common, but is easily dealt with if one is aware of it.

Humans↗

One- and two-dimensional pulse electron paramagnetic resonance spectroscopy: concepts and applications.

During the last two decades, the possibilities of pulse electron paramagnetic resonance (EPR) and pulse electron nuclear double resonance (ENDOR) spectroscopy have increased tremendously. While at the beginning of the 1980s pulse-EPR and ENDOR applications were still a rarity, the techniques are now very frequently applied in chemistry, physics, materials science, biology and mineralogy. This is mainly due to the considerable efforts invested in the last few years on instrument development and pulse-sequence design. Pulse-EPR spectrometers are now commercially available, which enables many research groups to use these techniques. In this work, an overview of state-of-the-art pulse EPR and ENDOR spectroscopy is given. The rapid expansion of the field, however, does not allow us to give an exhaustive record of all the pulse methods introduced so far. After a brief and very qualitative description of the basic principles of pulse EPR, we discuss some of the experiments in more detail and illustrate the potential of the methods with a number of selected applications.

Bacteriochlorophylls↗

[Optimizing laser parameters for intrastromal incision with ultra-short laser pulses].

BACKGROUND: With the assistance of ultrashort laser pulses (ca. 200 fs pulse duration) it is possible to perform precise incisions inside the corneal stroma with a width of a few microns. The advantage of ultrashort pulses is that the required energy of a few microjoules is more than an order of magnitude lower compared with longer pulse durations, i.e. ps or ns pulses. Therefore, the secondary effects, such as thermal and mechanical damage to the surrounding tissue and the amount of radiation reaching the retina, are reduced. This method of intrastromal photodisruption allows a very well defined deposition of energy within the laser focus inside the corneal stroma, accompanied by minimal collateral damage. METHODS: The possibilities of performing intrastromal cuts using fs-laser pulses at a wavelength of 780 nm and pulse durations of 200 fs were studied using a titanium-sapphire laser system. The treated tissue samples were analysed by light and scanning electron microscopy to determine incision quality, reproducibility and achievable accuracy. The mechanical side effects of fs-photodisruption inside the surrounding tissue were analysed by pressure measurements using pyroelectric transducers. CONCLUSION: The thermal and mechanical side-effects of this method are very low and comparable to the effects during excimer treatment. Therefore an application of ultrashort laser pulses in refractive surgery appears to be a feasible alternative.

Animals↗

Spectral content of the intraocular pressure pulse wave: glaucoma patients versus normal subjects.

BACKGROUND: Many studies have found that the intraocular pressure (IOP) is lower in glaucomatous populations than in normal groups. An alternative method of analysis, commonly used in the investigation of arterial blood pressure, is to reduce the pulse waveform to its component Fourier parts. The purpose of this study, therefore, was to determine whether such a technique is applicable to the IOP pulse and to investigate whether it was superior at differentiating diseased from healthy eyes. METHODS: Using a pneumatonometer, continuous 10-s IOP recordings were taken from 10 glaucoma patients and 10 normal subjects. The IOP recordings were then analysed using the fast Fourier transform (FFT) to determine their spectral components. In addition, standard IOP parameters (pulse amplitude, pulse volume, and pulsatile ocular blood flow) were measured to allow comparison with the waveform analysis technique. RESULTS: Analysis by FFT successfully determined the IOP pulse's higher spectral components up to the fourth harmonic. In addition, although standard measurements of the IOP pulse (such as pulse amplitude) were insignificant, the second ( P=0.034), third ( P=0.015) and fourth ( P=0.013) harmonics of the waveform successfully differentiated between the glaucoma and normal groups. CONCLUSION: Spectral analysis of the IOP pulse appears to be a promising technique in the investigation of ocular vascular disease.

Blood Pressure↗

Desynchronizing double-pulse phase resetting and application to deep brain stimulation.

Based on a stochastic phase-resetting approach, three different double-pulse stimulation techniques are presented here which make it possible to effectively desynchronize a population of phase oscillators in the presence of noise. In the three sorts of double pulses the first, stronger pulse restarts the cluster independent of its initial dynamic state. The three methods differ with respect to the mechanism through which the second, weaker pulse desynchronizes the cluster. Both first and second pulses are delivered to the same site. Because of the oscillators' global couplings in the model under consideration, the incoherent state is unstable, so that after the desynchronization the cluster tends to resynchronize. However, resynchronization is effectively blocked by repeated administration of a double pulse. The experimental application of double-pulse stimulation is explained in detail. In particular, demand-controlled deep brain double-pulse stimulation is suggested for the therapy of patients suffering from Parkinson's disease or essential tremor.

Calibration↗

Detection of movement artifact in recorded pulse oximeter saturation.

UNLABELLED: Movement artifact (MA) must be detected when analysing recordings of pulse oximeter saturation (SpO2). Visual analysis of individual pulse waveforms is the safest, but also the most tedious, method for this purpose. We wanted to test the reliability of a computer algorithm (Edentec Motion Annotation System), based on a comparison between pulse and heart rate, for MA detection. Ten 12-h recordings of SpO2, pulse waveforms and heart rate from ten preterm infants were analysed for the presence of MA on the pulse waveform signal. These data were used to determine the sensitivity and specificity of the computer algorithm, and of the oximeter itself, in detecting MA. Recordings were divided into segments of 2.5 s duration to compare the movement identification methods. Of the segments 31% +/- 6% (mean +/- SD) contained MA. The computer algorithm identified 95% +/- 3% of these segments, the pulse oximeter only 18% +/- 11%. Specificity was 85% +/- 4% and 99% +/- 0%, respectively. SpO2 was < or =80% in 3% +/- 1% of segments. 88% +/- 7% of the pulse waveform signal showed MA during this time, leaving a significant potential for erroneous identification of hypoxaemia. Recordings of SpO2 do not allow a reliable identification of MA. CONCLUSION: Without additional information about movement artifact, a significant proportion of recording time of pulse oximeter signal may be regarded as demonstrating hypoxaemia which, in fact, simply reflects poor measurement conditions. The computer algorithm used in this study identified periods of movement artifact reliably.

Algorithms↗

Water pulses and biogeochemical cycles in arid and semiarid ecosystems.

The episodic nature of water availability in arid and semiarid ecosystems has significant consequences on belowground carbon and nutrient cycling. Pulsed water events directly control belowground processes through soil wet-dry cycles. Rapid soil microbial response to incident moisture availability often results in almost instantaneous C and N mineralization, followed by shifts in C/N of microbially available substrate, and an offset in the balance between nutrient immobilization and mineralization. Nitrogen inputs from biological soil crusts are also highly sensitive to pulsed rain events, and nitrogen losses, particularly gaseous losses due to denitrification and nitrate leaching, are tightly linked to pulses of water availability. The magnitude of the effect of water pulses on carbon and nutrient pools, however, depends on the distribution of resource availability and soil organisms, both of which are strongly affected by the spatial and temporal heterogeneity of vegetation cover, topographic position and soil texture. The 'inverse texture hypothesis' for net primary production in water-limited ecosystems suggests that coarse-textured soils have higher NPP than fine-textured soils in very arid zones due to reduced evaporative losses, while NPP is greater in fine-textured soils in higher rainfall ecosystems due to increased water-holding capacity. With respect to belowground processes, fine-textured soils tend to have higher water-holding capacity and labile C and N pools than coarse-textured soils, and often show a much greater flush of N mineralization. The result of the interaction of texture and pulsed rainfall events suggests a corollary hypothesis for nutrient turnover in arid and semiarid ecosystems with a linear increase of N mineralization in coarse-textured soils, but a saturating response for fine-textured soils due to the importance of soil C and N pools. Seasonal distribution of water pulses can lead to the accumulation of mineral N in the dry season, decoupling resource supply and microbial and plant demand, and resulting in increased losses via other pathways and reduction in overall soil nutrient pools. The asynchrony of resource availability, particularly nitrogen versus water due to pulsed water events, may be central to understanding the consequences for ecosystem nutrient retention and long-term effects on carbon and nutrient pools. Finally, global change effects due to changes in the nature and size of pulsed water events and increased asynchrony of water availability and growing season will likely have impacts on biogeochemical cycling in water-limited ecosystems.

Carbon↗

Long-term mizoribine intermittent pulse therapy for young patients with flare of lupus nephritis.

Mizoribine (MZR) is a novel purine synthesis inhibitor that was developed in Japan. We previously reported the efficacy and safety of oral MZR intermittent pulse therapy, which is associated with elevated peak serum MZR levels, in selected patients with lupus nephritis. However, the efficacy and safety of long-term MZR intermittent pulse therapy (administered for over 24 months) in lupus nephritis patients at high risk for relapse has not yet been reported. Our study included five patients with a long history of systemic lupus erythematosus (SLE), including four patients with proliferative lupus nephritis (WHO class IV) and one patient with WHO class II lupus nephritis, in whom remission had been achieved through treatment with high-dose corticosteroids combined with cytotoxic agents. For the most recent flares, all the patients were treated with MZR intermittent pulse therapy without increase in the dose of corticosteroids. MZR was administered at 5-10 mg/kg per day (up to 500 mg) as a single daily dose on two days of the week (Monday and Thursday) for over 24 months. Concomitantly administered corticosteroid dose was gradually reduced or continued unchanged. At presentation, the urinary protein excretion, serum complement hemolytic activity (CH50) and serum anti-dsDNA antibody titer were 1.7+/-1.0 g/day, 16.6+/-3.8 U/mL (normal, 23-46 U/mL) and 143.7+/-151.1 IU/mL (normal,<12.0 IU/mL), respectively. At the latest observation point, after a mean interval of 31 months (24-34 months) after the initiation of MZR pulse therapy, the urinary protein excretion and serum anti-dsDNA antibody titer were significantly decreased (0.3+/-0.2 g/day and 18.5+/-19.1 IU/mL, respectively; P<0.05), and the serum CH50 value had returned to within normal range (33.6+/-7.8 U/mL, P<0.05). Despite the reduced minimum dose of prednisolone required to maintain clinical remission at the time of the post-treatment evaluation after MZR pulse therapy as compared with that at the time of the pretreatment evaluation (9.0+/-4.5 vs. 17.5+/-7.9 mg/day; P=0.0656), the calculated flare rate was significantly decreased (0.15+/-0.2 vs. 0.6+/-0.11 times per year; P<0.05). The serum creatinine level remained within normal range in all the study participants. Furthermore, the platelet count increased following the MZR pulse therapy in two patients who had suffered from chronic thrombocytopenia. No serious adverse effects were observed. From the view point of the balance between suppression of disease activity and the adverse effects of treatment, we believe that long-term MZR pulse therapy may be the treatment of choice in selected patients with lupus nephritis at high risk for relapse. However, this was only a pilot study conducted on a small number of subjects, without a control group. Further studies to confirm the long-term efficacy and safety of oral MZR intermittent pulse therapy in larger numbers of patients are needed.

Adolescent↗

Differences between cytotoxicity in photodynamic therapy using a pulsed laser and a continuous wave laser: study of oxygen consumption and photobleaching.

Oxygen consumption at the targeted site has a significant effect on dosimetry in photodynamic therapy (PDT). However, oxygen consumption in PDT using a pulsed laser as a light source has not been clarified. We therefore investigated the dependence of cytotoxicity on the oxygen consumption and the photosensitizer photobleaching of PDT using a pulsed laser by comparing with that using a continuous wave (CW) laser. Mouse renal carcinoma cells (Renca) were incubated with a second-generation photosensitizer, PAD-S31. The cells were then irradiated with either a 670-nm nanosecond pulsed light from the 3rd harmonics of a Nd:YAG laser-pumped optical parametric oscillator with a peak fluence rate of approximately 1 MW/cm(2) at 30 Hz or a 670-nm CW diode laser with a total light dose of 40 J/cm(2). Regardless of laser source, cytotoxic effects exhibited cumulative dose responses to the photosensitizer ranging from 12 to 96 microg/ml. However, cytotoxic effect of PDT using the pulsed light was significantly less than that using the CW light with the photosensitizer concentrations of 24 and 48 microg/ml under identical fluence rates. During PDT, the cells exposed to the pulsed light consumed oxygen more slowly, resulting in a lower amount of oxygen consumption when compared with PDT using CW light. In accordance with oxygen consumption, the pulsed light induced significantly less photobleaching of the photosensitizer than the CW light did. These results indicate that the efficiency of PDT using pulsed light is less when compared with CW light, probably being related to suppressed oxygen consumption during the pulsed light irradiation.

Animals↗

Effects of synaptic antagonists on perforant path paired-pulse plasticity: differentiation of pre- and postsynaptic antagonism.

The effects of different synaptic antagonists on paired-pulse plasticity of medial perforant path responses were studied in rat hippocampal slices. Baclofen reduces the response to activation of the perforant path, but does not have the same net effect on the first and second responses to paired stimulation: baclofen lessens the percent paired-pulse depression of medial perforant path responses. Furthermore, at doses that reduced the control medial perforant path response by half, paired-pulse plasticity changed from paired-pulse depression to paired-pulse potentiation. A similar effect on medial perforant path paired-pulse plasticity is produced by decreasing extracellular calcium concentration. Kynurenic acid reduces the first and second responses to paired stimulation proportionately the same, and, therefore, has no effect on the percent paired-pulse depression. These results suggest that baclofen acts presynaptically to reduce the synaptic response, whereas kynurenate acts postsynaptically. Adenosine was also found to be a potent antagonist of medial perforant path responses, with effects on paired-pulse plasticity similar to baclofen: a new synaptic antagonist, N-p-chlorobenzoyl-piperazine-2,3-dicarboxylate, was found to have effects like kynurenate, suggesting that it is also a postsynaptic receptor blocker.

Adenosine↗

Neurons in the inferior colliculus, auditory cortex and pontine nuclei of the FM bat, Eptesicus fucus respond to pulse repetition rate differently.

Single-neuron responses to pulse repetition rate in the inferior colliculus, auditory cortex and pontine nuclei of the FM bat, Eptesicus fuscus were studied under free-field stimulation conditions. The best frequency (BF) and minimum threshold (MT) of each neuron were first determined with a 4 ms pulse broadcast from a specific point (response center) of the bat's frontal auditory space at which the neuron had maximal spatial sensitivity. The neuron's intensity-rate function was then studied with a 4 ms BF pulse delivered at 10 dB increments above its MT in order to determine the best intensity to which the neuron discharged maximally. The neuron's discharge pattern and number of impulses to 32 trials of 300 ms train stimuli, which consisted of different number of 4 ms BF and best intensity pulses (1, 2, 3, 8, 12, 19, 24, 29 pulses/train) and delivered at an interpulse interval of 1000, 250, 170, 100, 40, 25, 15, 12 and 10 ms (i.e. at a pulse repetition rate of 1, 4, 6, 10, 25, 40, 67, 83, 100 pulses/s), were sequentially recorded. All neurons recorded from the inferior colliculus, auditory cortex and pontine nuclei discharged phasically (1-3 impulses) but they responded to the pulse repetition rate in different manners. More than 63% of 38 inferior collicular and 65 pontine neurons studied discharged impulses to each pulse within a train stimulus when the pulse repetition rate was up to 40 pulses/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Decreased heterosynaptic and homosynaptic paired pulse inhibition in the rat hippocampus as a chronic sequela to limbic status epilepticus.

We studied a rat model of chronic epilepsy that shares key features with certain patients with temporal lobe epilepsy. This model relies on a previous period of limbic system status epilepticus established by focal stimulation to one hippocampus. Animals were examined 1 month after recovery from such status epilepticus and compared to unstimulated controls and to animals that received stimulation but did not develop status epilepticus. Two experimental procedures were employed to study changes in paired pulse inhibition of population spike (PS) discharges elicited in CA1 pyramidal cells. One procedure (homosynaptic) delivered two identical stimuli to the CA3 region contralateral to the recording site; the other procedure (heterosynaptic) delivered a conditioning stimulus to the ipsilateral angular bundle and a separate test stimulus to the contralateral CA3. For both procedures, influences of stimulus intensities and of interpulse intervals on the potency of paired pulse inhibition were determined. Based on the results, standardized protocols that assayed the maximal amount of paired pulse inhibition were developed. With the homosynaptic protocol, there was one period of inhibition (interpulse intervals up to 300 ms). Animals that previously experienced limbic status epilepticus had markedly less paired pulse inhibition under these conditions than did controls. The stimulated, non-status epilepticus animals were not different from controls. For the heterosynaptic protocol, there were 2 phases of paired pulse inhibition, early (< 50 ms) and late (> 300 ms), separated by a period of paired pulse facilitation. After status epilepticus there were, compared to controls, decreases in both early and late phases of inhibition. The stimulated, non-status epilepticus animals were not different from controls. For the paired pulse facilitation, there was no difference between the animals that experienced status epilepticus and controls. These findings indicate a profound and enduring disturbance of GABA-mediated inhibition in this model. The heterosynaptic paired pulse protocol deals with a number of confounding issues associated with the homosynaptic protocol in this regard. Furthermore, the results suggest the inhibitory disturbance is diffuse, affecting various inhibitory circuits in the hippocampus.

Action Potentials↗