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D V Lewis

Publications and source records attributed to D V Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1989

Baclofen induces spontaneous, rhythmic sharp waves in the rat hippocampal slice.

In rat hippocampal slices, low concentrations of (+/-) baclofen (0.1 to 1.5 microM) elicited spontaneous, rhythmic sharp waves (SRSWs). These low amplitude (0.1 to 0.3 mV) SRSWs were visible with high amplification in the extracellular recordings from the CA1, CA2, and CA3 regions and were roughly synchronous in all areas. SRSW amplitude increased and frequency decreased as baclofen concentration increased up to 1.5 microM, but SRSWs were suppressed at concentrations of 5 microM and higher. The amplitude of the SRSWs was greater in the strata radiatum and the lacunosum moleculare than in the stratum pyramidale. (-)-Baclofen was much more potent in eliciting SRSWs than (+)-baclofen. Low concentrations of baclofen also caused the extracellular excitatory postsynaptic potential in the stratum radiatum of CA3b evoked by stimulation of the Schaffer collaterals to broaden and develop a secondary peak. Slices pretreated with pertussis toxin required much higher concentrations of baclofen to elicit the SRSWs, indicating that the baclofen may be eliciting the SRSWs through a G protein-sensitive mechanism. Baclofen has both inhibitory and disinhibitory effects on neurons. The appearance of these spontaneous population events suggests that, at low concentrations, the disinhibitory effects may be more powerful than the inhibitory effects.

Action Potentials↗
PubMed1989

Baclofen has a proepileptic effect in the rat dentate gyrus.

Effects of the gamma-aminobutyric acidB (GABAB) agonist baclofen on evoked responses and recurrent inhibition in the dentate gyrus were examined in rat hippocampal slices. Granule cell firing was induced by perforant path stimulation; recurrent inhibition was induced by pairing the perforant path stimulus with a preceding mossy fiber stimulus and was mediated through GABAA receptors. Whereas (+/-)-baclofen (10 microM) suppressed the perforant path-evoked population spike only about 20%, it suppressed recurrent inhibition about 84% and converted the perforant path-evoked response to an epileptiform response with multiple population spikes. These effects were concentration-dependent (estimated EC50 values for (+/-)-baclofen were 0.6 microM for suppression of recurrent inhibition and 1.0 microM for induction of multiple population spikes) and stereoselective for (-)-baclofen. Baclofen had no effect on GABAA-mediated inhibiton induced by focal application of GABA to the granule cells. These results suggest that baclofen suppressed recurrent inhibition through an action mediated by GABAB receptors on inhibitory interneurons. They also suggest the net effect of baclofen was proepileptic because its disinhibitory effect was substantially greater than its suppressive effect on synaptic excitation.

Animals↗
PubMed1988

A calcium-activated, nonselective cationic conductance in Aplysia silent neurons.

We have previously reported the activation of a triphasic current response by calcium injection in voltage-clamped, nonbursting neurons of Aplysia californica. Present evidence indicates that the second phase, a delayed inward current that peaks 10-20 seconds after the end of the injection, is a calcium-activated, nonselective cationic conductance. It can be carried by both sodium and calcium, is not sensitive to chloride concentration changes, but is voltage sensitive, decreasing in amplitude with hyperpolarization.

Animals↗
PubMed1988

Calcium-activated inward spike after-currents in bursting neurone R15 of Aplysia.

1. Slow inward and outward after-currents follow action potentials in the bursting pacemaker neurone, R 15, of Aplysia californica. These experiments were performed to examine the role of axo-dendritic calcium influx in activating these after currents. 2. Depolarizing voltage-clamp commands issued at the soma were used to elicit the after-currents. The earlier inward depolarizing after-current of DAC was followed by the hyperpolarizing after-current or HAC. The DAC and HAC appeared at a threshold following depolarizing commands in normal sea water, presumably due to triggering of action potentials in inadequately space-clamped axon. In 100 microM-tetrodotoxin (TTX), the after-currents were graded, increasing gradually in amplitude with increasing voltage or duration of the command. 3. After-current amplitudes varied with the holding potential through the range tested, -40 to -80 mV. DACs were maximum at -40 to -50 mV and decreased in amplitude with hyperpolarization. HACs were maximum at -40 mV and decreased with hyperpolarization to disappear between -70 and -80 mV. 4. The dependence of after-currents upon intracellular calcium accumulation during the depolarizing command was tested in several ways. Bathing R15 in 0 Ca2+-2 mM-EGTA (ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid) sea water eliminated the after-currents. Bathing in 1 mM-Ca2+ sea water reduced the DAC by 76% and the HAC by 87% following 10 ms long depolarizations to +40 mV. Application of Mn2+ (25 mM) or La3+ (5 mM) blocked the after-currents. Injection of EGTA intracellularly practically eliminated after-currents. Greatly prolonged depolarizations were required to elicit them after EGTA injection. Substitution of Ba2+ for Ca2+ also eliminated after-currents. 5. Sodium-free sea water eliminated the DAC. The HAC following brief (less than 30 ms) depolarizing commands was also eliminated in zero sodium, although longer commands were followed by an outward tail current. 6. Although the after-currents seemed dependent upon calcium influx, they were not suppressed by depolarizing commands whose voltage exceeded the calcium equilibrium potential at the soma as indicated by suppression of the calcium-activated potassium current, or IK(Ca), observed during the depolarization. However, if the extracellular calcium was lowered to 1 mM, large depolarizations did suppress the DAC. 7. Dopamine blocked the after-currents when applied to the axo-dendritic area but not when applied to the soma. Similarly, synaptic inhibition of long duration blocked the after-currents.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Seizure-like events in brain slices: suppression by interictal activity.

A major concern in epilepsy research is the relationship between ictal (seizure) electrophysiological activity and interictal (between seizure) activity. Much research is carried out in vitro using brain slice models. Although they allow detailed electrophysiology, the events recorded are generally more similar to interictal than ictal activity. We have described an in vitro model of epileptiform activity in the hippocampal slice (exposure to artificial cerebrospinal fluid containing no added magnesium) in which the events closely resemble those seen in vivo during seizures. However, this model is limited by the brief period during which this ictaform activity occurs before it is replaced by interictal-like activity. We now report that as the frequency of the interictal activity is suppressed by the GABAB agonist baclofen, the ictal activity returns. Moreover, when frequent interictal activity is reinduced, the ictal activity again is suppressed. These results suggest that interictal activity may decrease the probability of a seizure. Furthermore, they suggest that substances which may be shown to inhibit interictal activity in various models of epilepsy may not necessarily inhibit ictal activity.

Action Potentials↗
PubMed1987

Intractable complex partial seizures: the "initial motionless stare" and surgical outcome following temporal lobectomy.

Complex partial seizures (CPSs) beginning with an initial motionless stare (IMS) have been reported to respond well to temporal lobectomy. CPSs without the IMS or with early lateralizing motor phenomena often persisted after temporal lobectomy. We have studied video-EEG-recorded seizures of 18 patients with depth electrodes who then underwent temporal lobectomy. The IMS did not correlate with success or failure of surgery. However, initial head and/or eye deviation was correlated with poor surgical outcome.

Adolescent↗
PubMed1986

Magnesium-free medium activates seizure-like events in the rat hippocampal slice.

The effect of magnesium-free medium on the electrical activity in CA3 of the rat hippocampal slice was examined. Magnesium removal resulted in the development of spontaneous and triggered interictal-like bursting, followed by spontaneous ictal-like events and finally periodic clustered bursts. The ictal-like events consisted of a tonic firing phase and a phase of clustered burst discharges resembling the tonic and clonic phases of seizures. The return to normal medium resulted in spontaneous and triggered interictal-like bursts.

Action Potentials↗
PubMed1986

A novel, calcium-induced triphasic current response in silent, non-bursting Aplysia neurons.

The iontophoretic injection of Ca2+ ions into voltage-clamped, silent neurons of Aplysia californica results in a prolonged, triphasic current response. This response consists of: a tetraethylammonium-sensitive outward current during the injection; followed by an inward current 10-30 s after the end of the injection; and finally a long, slowly increasing outward current that lasts for several minutes before returning to baseline.

Animals↗
PubMed1986

Changes in cerebral blood volume and cytochrome aa3 during hypertensive peaks in preterm infants.

Relative changes in cerebral blood volume and in the oxidation/reduction state of cytochrome aa3, the terminal member of the electron transport chain in oxidative metabolism, can be simultaneously observed with near infrared spectroscopy. Using this technique, we studied movement-associated blood pressure elevations in three nonparalyzed very low birth weight infants receiving mechanical ventilation. We defined hypertensive peaks as increases in systolic and diastolic blood pressures greater than or equal to 30% over baseline and lasting at least 2 seconds. Ninety percent of monitored time, an increase in tissue blood volume (tBV) immediately followed each blood pressure elevation, with deoxygenated hemoglobin providing the sole or predominant increase in tBV. A simultaneous shift of cytochrome aa3 to a more reduced state usually accompanied the rise in tBV, probably indicating a transient imbalance between oxygen delivery and cellular oxygen utilization and a failure of mechanisms that normally regulate cerebral oxygenation. The consistent association of hypertensive peaks with body movement, coughing, and breath holding, and the predominant increase in deoxygenated hemoglobin suggest that increased intrathoracic pressure transiently impedes cerebral venous return. The repeated fluctuations in intracerebral blood volume and associated shifts to greater cytochrome aa3 reduction with hypertensive peaks provide a possible explanation for the association of fluctuating blood pressure patterns and increased risk for intraventricular hemorrhage.

Blood Volume↗
PubMed1986

Juvenile acute intermittent porphyria with hypercholesterolemia and epilepsy: a case report and review of the literature.

A case of acute intermittent porphyria in a 10-year-old boy with seizures and hypercholesterolemia is presented. The problems of management when seizures and porphyria coincide and discussion of hypercholesterolemia are included. A comprehensive review of the world literature reveals that prepubertal patients with acute intermittent porphyria are predominantly male and show an increased incidence of seizures when compared to older age groups. The principal clinical features in all age groups include abdominal pain, vomiting, fever, and tachycardia in addition to mental changes, limb paresis, and hyporeflexia.

Child↗
PubMed1986

Membrane currents underlying bursting pacemaker activity and spike frequency adaptation in invertebrates.

Invertebrate systems have proved to be quite useful for the development of an understanding of some processes in the central nervous system (CNS). An understanding of the basic mechanisms of epilepsy will result from understanding not only how populations of neurons interact but also how the physiological processes in individual neurons are altered in epileptogenesis. Because invertebrate neurons have been so accessible to experimentation, it has been possible to explore in detail the basic mechanisms controlling neuronal excitability using these cells and to make some useful predictions about electrophysiological mechanisms that may be present in central neurons. This chapter deals with two electrophysiological processes that have been observed in invertebrate neurons and that may have some relevance to understanding the basic mechanisms of epilepsy. We review first the past and current studies of invertebrate burst firing neurons. It appears that the electrophysiological mechanisms producing burst firing may be present in CNS neurons participating in epileptogenesis. With caution, the information gleaned from invertebrate studies may be applicable to higher systems. The second process we consider is the phenomenon of spike frequency adaptation seen in invertebrates. Spike frequency adaptation is the process by which the firing rate of the neuron declines despite the maintenance of a constant stimulus. This process is not so thoroughly studied as burst firing, but it appears to represent a cellular mechanism designed to suppress prolonged periods of repetitive firing. Clearly, the suppression of such a process would produce excessive neuronal excitability, while its enhancement might have some anticonvulsant effects. The extreme sensitivity of spike frequency adaptation to barbiturates suggests such a possibility. These two electrophysiological processes are interesting in themselves and also because they may underlie the genesis or control of seizures. However, the greater significance is that, to understand the basic mechanisms of epilepsy, we may be well advised to examine neuronal processes in systems not considered to have seizure susceptibility.

Action Potentials↗
PubMed1985

The ionic mechanism of the slow outward current in Aplysia neurons.

A slow outward current associated with spike frequency adaptation has been studied in the giant Aplysia neurons R2 and LP1. The current was observed during 60-s voltage clamp commands to potentials just below spike threshold. The slow outward current shows a marked voltage dependence at membrane potential less negative than -40 mV. The slow outward current is associated with increased membrane conductance. The K+ sensitivity of the slow outward current was studied by varying the extracellular K+ concentration and also by measuring potassium efflux with a K+-sensitive electrode. Both procedures indicated that the slow outward current was K+ dependent. Tail currents following the activation of the slow outward current were examined. They were shown to have a similar potassium sensitivity as the slow outward current and had a reversal potential near the potassium equilibrium potential for these cells. The sensitivity of the slow outward current to known blockers of K+ currents, tetraethylammonium and 4-aminopyridine, was tested. The sensitivity was much less than that reported for other K+ currents. The sensitivity of the slow outward current to changes of the extracellular concentrations of Na+ and Cl- ions, as well as electrogenic pump inhibitors, was tested. The results indicate that the slow outward current is much less sensitive to these changes than to the manipulations of the extracellular K+ ion concentration. We tested the sensitivity of this current to manipulations of intracellular and extracellular Ca2+ ion concentrations. We found that the current persisted at a slightly reduced level in the absence of extracellular calcium or in the presence of calcium blocking agents, cobalt and lanthanum. Intracellular injection of the calcium chelator EGTA at a concentration sufficient to block the Ca2+-dependent K+ current, seen after a brief (1.4-s) burst of action potentials, had minimal effects on the slow outward current. Procedures thought to increase intracellular Ca2+ were tested. We found that exposure of the cell to solutions containing elevated Ca2+ concentrations for prolonged periods increased the slow outward current. Also, treatment with drugs thought to elevate intracellular Ca2+ increased the slow outward current. In conclusion, the slow outward current results from an increased K+ conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Noninvasive monitoring of cerebral oxygenation in preterm infants: preliminary observations.

A noninvasive optical method for bedside monitoring of cerebral oxygenation in small preterm infants was evaluated. Through differential absorbance of near infrared light, changes in the oxidation-reduction level of cytochrome aa3, in the oxygenation state of hemoglobin and in tissue blood volume were assessed in the transilluminated anterior cerebral field. Overall, cerebral oxygenated hemoglobin correlated significantly with transcutaneous oxygen, r = .44 p less than .0001; however, correlation was best in the absence of cardiorespiratory disease. Hypoxia with or without bradycardia led to hemoglobin deoxygenation and a shift in cytochrome aa3 to a more reduced state. When hypoxic episodes came in series or were prolonged, aa3 reduction occurred simultaneous with hemoglobin deoxygenation but its recovery to base-line values sometimes lagged behind the return of hemoglobin oxygenation. In one infant with a large patent ductus arteriosus, even brief episodes of mild bradycardia caused precipitous reduction of cytochrome aa3 before any shift to greater hemoglobin deoxygenation. This response disappeared after ductal ligation. In general, the antecedent state of cerebral oxygenation, the severity and duration of deoxygenation, and the presence or absence of circulatory abnormalities all influenced the aa3 response to hypoxia. Continuous noninvasive near infrared monitoring of cerebral oxygenation can be performed on sick preterm infants at the bedside.

Blood Volume↗
PubMed1984

Spike aftercurrents in R15 of Aplysia: their relationship to slow inward current and calcium influx.

Spikes in the bursting neuron, R15, are followed by depolarizing afterpotentials (35) and often by delayed hyperpolarizing afterpotentials as well. Placing the cell in a voltage clamp after a spike allows measurement of the depolarizing aftercurrent (DAC) and hyperpolarizing aftercurrent (HAC) that underlie the afterpotentials. Subthreshold depolarizations give rise to small DACs and HACs. The DAC and the slow inward current (SIC) of R15 are reduced or blocked in a similar manner by many experimental manipulations, e.g., application of dopamine, zero-calcium seawater, zero-sodium seawater, or calcium-channel blockers (Mn2+ and La3+), or cooling the cell from 21-22 degrees C to 10 degrees C. Neither the DAC nor the SIC were blocked by tetrodotoxin (100 uM) and neither was sensitive to altered extracellular potassium. Both the DAC and SIC become larger as the holding potential of the cell is progressively depolarized from -70 to -40 mV. DACs are sensitive to the injection of intracellular calcium chelators (EGTA (ethylene glycol-bis(beta-aminoethyl ether)-N,N1-tetraacetic acid) or EDTA [ethylenedinitrilo)tetraacetic acid]. DAC amplitude is approximately 90% reduced by intracellular EGTA concentration near 1mM. In contrast, the SIC is unchanged or much less affected by the calcium buffers. DACs are also more sensitive to low (1 mM) extracellular calcium than is the SIC. The HAC is also a calcium-dependent current. It is blocked by any experimental manipulation reducing calcium influx or intracellular calcium accumulation, i.e., reduced extracellular calcium, calcium-channel blockers, or intracellular EGTA. We suggest that the DAC and the SIC are carried by the same conductance mechanism. In the case of the DAC, the conductance might be activated by a rise in intracellular calcium activity accompanying the spike and, in the case of the SIC, depolarization per se may be the most important activating condition.

Abdomen↗
PubMed1984

Dopamine reduces slow outward current and calcium influx in burst-firing neuron R15 of Aplysia.

Dopamine's effect on calcium influx into the bursting neuron, R15, of Aplysia californica was tested by tail current measurements and by measurement of absorbance of intracellular Arsenazo III, a calcium-sensitive indicator. Slow outward tail currents were elicited by subthreshold depolarization in voltage clamp and were demonstrated to be dependent upon transient increases in intracellular calcium activity, (Ca)i), using calcium-free seawater, calcium blockers (Mn2+ and La3+), and intracellular injection of EGTA. Dopamine reduces these tail currents as it reduces the slow inward current. Next, the transient elevations of (Ca)i accompanying subthreshold depolarization were measured directly in Arsenazo III-loaded neurons. Dopamine did not reduce the rise in (Ca)i measured in the soma during depolarization. However, when absorbance of the axodendritic region was monitored, dopamine did reduce calcium influx. Voltage monitoring in the axon indicated that the reduced calcium influx could not simply be ascribed to altered space clamp. In keeping with the apparent axodendritic location of dopamine action, isolation of the soma by ligation of the axon markedly reduced the dopamine response. Dopamine seems to reduce calcium influx into R15, but this effect is topographically limited to nonsomatic membrane, an area of the neuron not usually monitored in optical studies of (Ca)i.

Animals↗