Biomedical subjects

F E Dudek

Publications and source records attributed to F E Dudek.

At least 109 records · Page 6Linked to original sources

PubMed1987

Unresponsive, a behavioral mutant in Xenopus laevis: electrophysiological studies of the neuromuscular system.

Normal Xenopus laevis embryos begin movements at 1 day after fertilization. Embryos homozygous for the unresponsive mutation fail to move until 4 days after fertilization (just prior to feeding), after which they recover slowly. Electrophysiological studies were undertaken to determine the focus of this mutation. Formamide treatment of normal embryos was used to produce a phenocopy of the unresponsive condition, permitting direct comparisons between mutant and normal embryos. Intracellular recordings from muscle cells were obtained in formamide-treated and untreated preparations with both normal and unresponsive animals. Local electrical stimulation evoked either isolated endplate potentials and action potentials or after-discharges of these events in all preparations. A decrease in illumination also caused a burst of endplate potentials and action potentials. Therefore, the electrophysiology of the neuromuscular junction in unresponsive appears qualitatively normal; the effect of the mutation on the motor system is probably distal to the neuromuscular junction, either at or subsequent to excitation-contraction coupling.

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PubMed1987

Synaptic activation of slow depolarization in rat supraoptic nucleus neurones in vitro.

1. The effects of synaptic activation on rat supraoptic nucleus (s.o.n.) neurones were studied in the hypothalamic slice preparation. Intracellular recordings were obtained from forty-one probable magnocellular neuroendocrine cells using microelectrodes filled with 3 M-potassium acetate. Responses to single and repetitive stimulation of the area dorsolateral to the s.o.n., which would be expected to activate a cholinergic pathway (Hatton, Ho & Mason, 1983), were analysed. 2. In forty of forty-one cells, responses to single stimuli consisted of a short-latency excitatory post-synaptic potential (e.p.s.p.), which was often followed by a brief burst of fast depolarizing events which resembled spontaneous e.p.s.p.s. When the membrane was depolarized, single stimuli could consistently produce a burst of action potentials. 3. Brief trains of orthodromic stimuli produced three effects in most cells. Spontaneous fast depolarizing events, which appeared to be primarily e.p.s.p.s. significantly increased in frequency after the train. A slow membrane depolarization, which lasted up to 1-2 min, was observed in twenty-eight of forty-one cells. In several cells the slow depolarization was accompanied by an increase in input resistance (Ri). In some cells an after-discharge occurred during the slow depolarization. Slow depolarizations were observed in each of eleven phasic neurones, and in a smaller percentage of non-phasic and silent cells. 4. All components of the response to dorsolateral stimulation could be reduced or blocked in low-Ca2+, high-Mg2+ bathing medium. 5. Slow depolarizations were observed when action potentials were not elicited by the stimulus train. The slow depolarization was still present after manipulations that blocked discharge during the stimulus train, including injection of hyperpolarizing current and diffusion of the quaternary ammonium compound QX314. These data argue that the slow depolarization can occur independent of spike depolarizing after-potentials (d.a.p.s). 6. In some cells antidromic stimulation at an intensity just suprathreshold for the recorded cell did not produce comparable bursts of fast depolarizing events or slow depolarizations; similar periods of depolarizing current injection, which produced repetitive discharge, also did not mimic the effects of orthodromic stimulation. 7. The fast depolarizing events appear to reflect spontaneous e.p.s.p.s; increases in the frequency of these events may reflect the after-discharge of nearby neurones that are presynaptic to the recorded neurone.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1986

Evidence for neuronal interactions by electrical field effects in the CA3 and dentate regions of rat hippocampal slices.

During population spikes in slices of rat hippocampus, transmembrane differential recordings (intracellular minus extracellular) revealed electrical field-effect depolarizations in CA3 pyramidal and dentate granule neurons. The field-effect depolarizations were not seen in single-ended recordings, and were consistently shown to increase neuronal excitability. Therefore, as previously shown for the CA1 area, large population spikes from CA3 pyramidal and dentate granule cells are associated with transmembrane depolarizations that increase neuronal excitability.

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PubMed1986

Role of electrical interactions in synchronization of epileptiform bursts.

Four general mechanisms can hypothetically contribute to or mediate localized synchronization of neuronal activity: (a) recurrent excitatory chemical synapses, (b) electrotonic coupling via gap junctions, (c) electrical field effects (ephaptic interactions), and (d) changes in the concentration of extracellular ions (e.g., K+). It has generally been believed that synchronization of epileptiform bursts derives primarily, if not exclusively, from recurrent excitatory chemical synapses. Dual intracellular recordings from the CA3 area of the hippocampus have been used to demonstrate the existence of recurrent synaptic excitation, and computer simulations have provided a theoretical framework for the idea that relatively sparse interactions through recurrent excitatory chemical synapses can generate synchronized bursting after inhibitory pathways are blocked with convulsant agents. Additional experimental studies have supported the hypothesis that a model for seizure discharge, the penicillin-induced paroxysmal depolarization shift (PDS), is associated with a large increase in excitatory synaptic conductance. However, recent studies have suggested that electrical interactions are also likely to play an important role in spike synchronization during epileptic discharges. Several research groups have used in vitro preparations to show that afterdischarges and spontaneous bursts of population spikes (which represent synchronized action potentials) can occur after chemical synaptic transmission has been blocked in solutions containing low [Ca2+]. Although this result was first observed in the CA1 area, it has recently been confirmed in other regions of the hippocampus. These experiments indicate that mechanisms other than chemical synaptic transmission are capable of synchronizing action potentials in the hippocampus. In this chapter, two forms of electrical interaction that could mediate synchronization will be considered: (a) electrotonic coupling through gap junctions and (b) electrical field effects through extracellular space. Changes in the concentration of extracellular ions are another mechanism not involving chemical synapses. However, it seems unlikely that ionic changes act on the rapid time scale of electrical interactions, and their contribution is discussed elsewhere in this volume. We review evidence for the existence of electrotonic coupling and electrical field effects in the hippocampus and neocortex, and discuss their possible involvement in the synchronization of epileptiform events.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1986

The effects of lead exposure on field potentials of CA3 pyramidal cells from mossy fiber stimulation in rat hippocampus.

Previous anatomical evidence indicates that lead (Pb) alters development of the hippocampus and electrophysiological data suggest that Pb interferes with several neuronal systems outside the hippocampus. The present research was undertaken to examine the possibility that exposure to Pb early in development induces electrophysiological alterations in field potentials of CA3 pyramidal cells. Rat pups were exposed to Pb for the first 25 days of age via maternal milk. During this period, dams were fed diets containing either 4% PbCO3 or a Na2CO3 control diet. At 39-54 days of age, 15 sec trains of 20 Hz electrical stimuli at near-maximal intensities were delivered to the dentate granule cells of anaesthetized rats. No significant differences between Pb-treated and control animals were detected for the evoked responses during or after the stimulus trains. However, spreading depression was observed in a greater proportion of Pb-treated animals and more frequently within single Pb-treated animals than in controls. Repetitive bursting, which followed termination of most 20-Hz trains, was significantly longer for Pb-treated animals. The duration of single bursts and the interval between bursts in a given episode were also longer in Pb-treated animals. These data support the hypothesis that developmental Pb exposure alters the electrophysiological properties of CA3 pyramidal cells.

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PubMed1985

Spike broadening in magnocellular neuroendocrine cells of rat hypothalamic slices.

Bursts of action potentials recorded from rat magnocellular neuroendocrine cells (MNCs) are known to be associated with enhanced release of oxytocin or vasopressin from their axon terminals in the neurohypophysis. Intracellular recordings from MNC somata in hypothalamic slices showed that spike broadening was characteristic of such bursts. Transitions from slow to fast firing caused spike broadening in all cells, whether they were silent, slow firing, phasic or fast-continuous. During phasic firing, broadening increased with the intraburst spike frequency. However, the parameters of maximal spike broadening recorded at the soma did not directly coincide with the previously described firing patterns evoking maximal hormone release from neurohypophysial terminals.

Action Potentials↗

PubMed1985

Effects of phenytoin on field bursts of rat hippocampal slices in low-calcium solutions.

Recurring bursts of population spikes, a simple model of epileptiform activity, can be produced by exposing slices of rat hippocampus to saline containing 0.2 mM [Ca2+] and 4.0 mM [Mg2+], at which concentration chemical synaptic activity is blocked. Phenytoin at 7.3-73 microM shortened the duration of these bursts. At 73 microM the bursts were slowed and often eliminated. This model appears to be more sensitive to the action of phenytoin than the penicillin model of epileptiform bursting.

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PubMed1985

Computer simulations indicate that electrical field effects contribute to the shape of the epileptiform field potential.

In the presence of convulsant drugs such as picrotoxin, neurons in the hippocampal-slice preparation generate synchronized depolarizing bursts. This synchrony occurs on a time scale of tens of milliseconds and is produced by excitatory synaptic interactions between neurons. The synaptic interactions themselves occur on a time scale of tens of milliseconds. The "epileptiform" local-field potential during such synchronized bursts is comb-shaped ("ringing"), whereas the field potential expected if action potentials in neighboring neurons were uncorrelated is noisy and not comb-shaped. This suggests that individual action potentials are locally synchronized on a time scale of 1 ms. We have previously shown, using computer simulations, that electrical interactions--mediated by currents flowing in the extracellular medium--can plausibly explain action-potential synchronization in experiments where chemical synapses are blocked. The present simulations demonstrate that electrical interactions can also account for action-potential synchronization--and thus the "ringing" shape of the field potential--during epileptiform bursts, where excitatory synapses are functional. The field potential is thus a modulating influence on, as well as a reflection of, underlying neuronal transmembrane events.

Action Potentials↗

PubMed1985

Simulation of hippocampal afterdischarges synchronized by electrical interactions.

Recent experiments have shown that hippocampal pyramidal cells can generate synchronized action potentials even when chemical synapses are blocked. The computer simulations reported here showed that communication between cells by extracellular currents could cause this synchrony, provided that (1) individual neurons were sufficiently excitable and that (2) the resistivity of the extracellular medium was sufficiently high. Synchronization was enhanced if electronic junctions were also present.

Action Potentials↗

PubMed1984

Electrical fields directly contribute to action potential synchronization during convulsant-induced epileptiform bursts.

Synchronous field-potential bursts were induced in hippocampal slices with picrotoxin. Differential recording between intracellular and adjacent extracellular electrodes during paroxysmal depolarization shifts revealed rapid transmembrane depolarizations (TMDs), which were spike prepotentials generated by electrical field effects. These experiments demonstrate that endogenous electrical fields contribute to spike synchronization in the presence of convulsant drugs when excitatory chemical synapses are functional.

Action Potentials↗

PubMed1984

Synchronous epileptiform bursts without chemical transmission in CA2, CA3 and dentate areas of the hippocampus.

Slices of rat hippocampus maintained in a medium containing Mn2+ and lowered Ca2+ concentration, which demonstrably blocked chemical synapses, generated spontaneous bursts of population spikes in all cell body layers after 30-60 min of incubation. Therefore, electrical interactions alone can synchronize neuronal activity in the hippocampus, and they are probably important during epileptiform events.

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PubMed1984

Intrinsic inhibition in magnocellular neuroendocrine cells of rat hypothalamus.

Endogenous mechanisms of inhibition in magnocellular neuroendocrine cells were studied with intracellular recordings in the rat hypothalamic slice preparation. Hyperpolarizing after-potentials (duration up to 125 ms) followed single action potentials and after-hyperpolarizations (a.h.p.s) lasting hundreds of milliseconds followed brief evoked spike trains. The amplitude and duration of the a.h.p. increased after spike trains of longer duration or higher frequency. The a.h.p. appears endogenous, rather than synaptically mediated from recurrent inhibition, because it persisted after pharmacological blockade of axonal conduction or of chemical synaptic transmission. The reversal potential of the a.h.p. was at least 20 mV more negative than that of inhibitory post-synaptic potentials. Cl- ionophoresis did not alter the a.h.p. Chelation of intracellular Ca2+ with EGTA injection eliminated the a.h.p. A Ca2+-activated K+ conductance, rather than recurrent synaptic inhibition, apparently causes the a.h.p. and is at least partly responsible for the inhibition after single spikes in magnocellular neurones. During hormone release, this endogenous mechanism may contribute to the post-burst silent period in putative oxytocinergic cells and to the interburst interval in phasic neurones, which are known to fire repetitive bursts associated with vasopressin release.

Action Potentials↗

PubMed1984

Analysis of intracellularly recorded phasic bursting by mammalian neuroendocrine cells.

Phasic bursting by magnocellular neuroendocrine cells (MNCs) in the mammalian supraoptic and paraventricular nuclei (SON and PVN) consists of successive periods of action potentials and inactivity. It has previously been correlated with increased release of vasopressin from the neurohypophysis. In the present studies we investigated the neuronal mechanisms underlying this firing pattern. Using coronal slices of rat hypothalamus, we recorded intracellularly from neurons that are considered to be MNCs, based on several criteria. Eight of the 29 cells in this study displayed phasic burst patterns similar to those previously recorded extracellularly from MNCs in intact animals. Among the eight phasic cells, low levels of steady current injection could dramatically alter burst periodicity. Steady hyperpolarization revealed patterned synaptic input in only one case; in the remainder of the cells, nonsynaptic mechanisms appeared to account for periodic bursting. The phasic burst pattern usually appeared to be spike dependent, each burst arising from one or several depolarizing after-potentials (DAPs). Summed DAPs formed a plateau potential, which provided a depolarizing drive for further spiking. Spike frequency decreased late in the burst, and then the plateau potential terminated. During the quiescent period, burst excitability appeared to increase coincident with a small slow depolarization. Spikes and their summating DAPs could then initiate another burst. In several silent MNCs, a brief supra-threshold current pulse could initiate a prolonged afterdischarge, which had the properties of a phasic burst. Two MNCs that fired with a fast-continuous pattern were tested with brief hyperpolarizing current pulses; after each pulse, spike activity ceased and a plateau potential was revealed. Therefore, it appears that a maintained plateau potential (summed DAPs) can drive fast-continuous firing. In one case a periodic bombardment of excitatory postsynaptic potentials (EPSPs) generated a phasic firing pattern. The dependence of the burst characteristics on membrane potential, the apparent lack of patterned synaptic input in most cells, and the ability to evoke bursts with brief stimuli support the hypothesis that bursting in some MNCs involves an endogenous mechanism. Furthermore, phasic firing may be driven by tonic excitatory input. The data on phasic, silent, and fast-continuous cells suggest that many MNCs can generate DAPs and plateau potentials.

Action Potentials↗

PubMed1984

Excitation of hippocampal pyramidal cells by an electrical field effect.

The effects of electrical fields from antidromic stimulation of CA1 pyramidal cells were studied in slices of rat hippocampus in which chemical synaptic transmission had been blocked by superfusion with physiological solution containing Mn2+ and lowered concentration of Ca2+. Differential voltage recordings were made between two microelectrode positions, on intracellular to a pyramidal cell and the other in the adjacent extracellular space. This technique revealed brief transmembrane depolarizations that occurred synchronously with negative-going extracellular population spikes in the adjacent cell body layer. Glial cells in this region did not exhibit these depolarizations. In some pyramidal cells, alvear stimulation that was too weak to excite the axon of the impaled cell elicited action potentials, which appeared to arise from transmembrane depolarizations at the soma. When subthreshold transmembrane depolarizations were superimposed on subthreshold depolarizing current pulses, somatic action potentials were generated synchronously with the antidromic population spikes. The depolarizations of pyramidal somata were finely graded with stimulus intensity, were unaffected by polarization of the membrane, and were not occluded by preceding action potentials. The laminar profile of extracellular field potentials perpendicular to the cell body layer was obtained with an array of extracellular recording locations. Numerical techniques of current source-density analysis indicated that at the peak of the somatic population spike, there was an extracellular current sink near pyramidal somata and sources in distal dendritic regions. It is concluded that during population spikes an extracellular electrical field causes currents to flow passively across inactive pyramidal cell membranes, thus depolarizing their somata. The transmembrane depolarizations associated with population spikes would tend to excite and synchronize the population of pyramidal cells.

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PubMed1984

Synchronization without active chemical synapses during hippocampal afterdischarges.

Afterdischarges elicited by antidromic stimulation were studied in the CA1 region of transverse slices of rat hippocampus. The slices were incubated in a static bathing medium containing Mn2+ with lowered Ca2+ concentration, which blocked chemical synaptic transmission. Extracellular voltage recordings from micropipettes revealed afterdischarges of population spikes, which represent synchronized action potentials. Afterdischarge duration became longer with incubation time, occasionally lasting up to 9 s. Simultaneous recordings from three extracellular micropipettes indicated propagation of individual population spikes along the CA1 cell body layer during an afterdischarge. Intracellular recordings from pyramidal cells showed that action potentials were synchronized with population spikes. When initial action potentials of an afterdischarge were blocked by hyperpolarizing the impaled cell, subsequent action potentials remained synchronized with population spikes, indicating a synchronizing interaction between neurons. Intrasomatic neuronal recordings sometimes revealed partial action potentials that were also synchronized with population spikes. During afterdischarges, relatively weak (10 mV) hyperpolarization blocked both full and partial action potentials. These observations suggest that synchronized action potentials and partial spikes were initiated near the soma. Intracellular voltage recordings were referenced to a local extracellular microelectrode in order to determine more accurately the transmembrane potential in the presence of large population spikes .54). Such neuronal recordings revealed brief transmembrane depolarizations that occurred synchronously with population spikes. Large injected hyperpolarizing currents did not affect the brief transmembrane depolarizations. Similar differential voltage recordings across glial cell membranes did not show measurable brief transmembrane depolarizations during population spikes. However, slow glial depolarizations during afterdischarges indicated prolonged K+ accumulation and clearance in the extracellular space, which probably contributed to the hyperexcitability of pyramidal cells. During an afterdischarge, extracellular potentials were recorded simultaneously from six micropipettes arranged perpendicularly to the stratum pyramidale. Current source-density analysis indicated a sink in the cell body layer during population spikes and a corresponding source in distal dendrites. It is concluded that an electrical field effect depolarizes and thus synchronizes neurons during these afterdischarges.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1983

Burst discharge in mammalian neuroendocrine cells involves an intrinsic regenerative mechanism.

Intracellular recordings from mammalian neuroendocrine cells showed that steady, injected currents can modify and block periodic spike bursts previously associated with increased neurohormone release. Spike afterpotentials could sum to form plateau potentials, which generated bursts and did not depend on axonal conduction or chemical synapses. Therefore, bursting involves a spike-dependent, positive-feedback mechanism endogenous to single neuroendocrine cells.

Action Potentials↗

PubMed1983

Egg-laying hormone: direct action on the ovotestis of Aplysia.

The bag cells are a group of neuroendocrine cells located in the abdominal ganglion of Aplysia californica. These cells induce egg laying in the animal through the release of neurohormone(s). Previous experiments established that an extract of bag cells releases eggs from isolated ovotestis fragments in a dose-dependent manner. (F. E. Dudek and S. S. Tobe, 1978, Gen. Comp. Endocrinol. 36, 618-627.) Experiments presented here were conducted to purify and identify the component(s) of bag cell extract with the egg-releasing activity. Bag cell extracts were fractionated by means of gel-filtration chromatography followed by cation-exchange chromatography. Column eluates were assayed for egg-release activity on isolated ovotestis fragments by the method of Dudek and Tobe (1978). Only one component purified from the crude extract had egg-releasing activity. This component was identified as egg-laying hormone (ELH) based on its purification characteristics, effects on neuronal activity, and migration on thin-layer chromatography. In dose-response studies egg release increased with the concentration of ELH and had a threshold of 8 X 10(-10) M or less. ELH had the same dose-response relationship in egg release assays when present in purified form or as a component of bag cell extract. These data show that ELH acts directly on the ovotestis and that ELH is the only component of bag cell extract with egg-release activity. Taken with the results of other studies (W. D. Branton, S. Arch, T. Smock, and E. Mayeri, 1978. Proc. Nat. Acad. Sci. USA 75, 5732-5736. B. S. Rothman, P. Brownell, and E. Mayeri, 1979. Soc. Neurosci. Abstr. 5, 260. E. Mayeri and B. S. Rothman, 1982.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1983

Electrophysiological and optical changes in slices of rat hippocampus during spreading depression.

Spreading depression (SD) was studied with intracellular and extracellular recordings and with photometry in slices of rat hippocampus. Repetitive electrical stimulation could initiate SD in either normal medium or in low-Ca2+ medium containing Mn2+, especially during transient hypoxia. The extracellular voltage near CA1 pyramidal somata and dendrites became negative by approximately 18 mV during SD. This negativity peaked more slowly in low-Ca2+ medium containing Mn2+. The wave of negativity propagated across the slice in both media at approximately 6 mm/min. Input resistance of pyramidal neurons became undetectable during SD, and differential voltage recording between neurons and adjacent extracellular space demonstrated that transmembrane potential approached zero. Slices became more opaque during SD. Photometry revealed approximately 10% increase in reflectance and a similar decrease in transmittance of white light, which occurred with a time course similar to the extracellularly recorded voltage shift. These data support the hypothesis that SD represents a large increase in membrane permeability associated with substantial movements of water. The persistance of SD in a bathing solution that blocked electrically evoked postsynaptic potentials suggests that the contribution of synaptic transmitter release to the propagation of SD should be reappraised.

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