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Biomedical subjects

D A Prince

Publications and source records attributed to D A Prince.

At least 127 records · Page 7Linked to original sources
PubMed1981

Human epileptic neurons studied in vitro.

The in vitro neocortical brain slice technique was used to study electrophysiological properties of neurons from brain biopsies in 10 patients undergoing neurosurgical treatment for a variety of conditions, including focal epilepsy. The principal finding was the occurrence of orthodromically evoked depolarization shifts (DSs) and burst discharges in a proportion of neurons in slices from epileptogenic cortex. These evoked depolarizations and bursts had a number of properties in common with those from experimental epileptogenic foci in neocortex, including large amplitude and prolonged duration; long and variable latencies; and all or none, threshold type behavior, dependent on the parameters of orthodromic stimulation. Also DSs could not be evoked by intracellular stimulation, or blocked by hyperpolarizing current pulses once they had been orthodromically evoked. Responses of DSs to current thus differed markedly from those of neurons in epileptogenic guinea pig hippocampal slices. The results of these experiments suggest that intracellular events in human neurons involved in epileptogenesis are similar in appearance to those in various animal models. Neurons in chronic epileptogenesis are similar in appearance to those in various animal models. Neurons in chronic epileptogenic foci retain some of their abnormal properties within brain slices maintained in vitro.

Cell Membrane↗
PubMed1981

Dye coupling and possible electrotonic coupling in the guinea pig neocortical slice.

Iontophoretic injection of the fluorescent dye Lucifer Yellow CH into single neurons of guinea pig neocortical slices resulted in the staining of more than one cell. Dye-coupled neuronal aggregates were found only in the superficial cortical layers and were often organized in vertical columns. Antidromic stimuli evoked all-or-none, subthreshold depolarizations in some superficial cells. These potentials were not eliminated by manganese and did not collide with spikes originating in the soma, suggesting that they arose from electrotonic interaction between superficial cortical neurons.

Action Potentials↗
PubMed1981

Penicillin- and barium-induced epileptiform bursting in hippocampal neurons: actions on Ca++ and K+ potentials.

Both barium (Ba++) and penicillin produce spontaneous epileptiform burst generation in hippocampal neurons in vitro. Recent investigations suggest that Ba++ acts by both adding to a calcium (Ca++)-mediated depolarization and reducing potassium (K+) conductance. In contrast, it has been proposed that penicillin produces burst generation by attenuating inhibitory postsynaptic potentials. However, some evidence suggests that penicillin may also directly alter intrinsic membrane properties. We therefore compared the actions of penicillin and Ba++ on three intrinsic Ca++- or K+-mediated membrane events, namely, CA++ spikes, Ca++-dependent anomalous rectification, and K+-dependent afterhyperpolarization. Ba++ augmented the Ca++ potentials and attenuated the K+-dependent afterhyperpolarization; penicillin had no demonstrable effect on these events. Ba++ produced rhythmical burst firing and oscillations of the membrane potentials, while penicillin caused sporadic burst generation followed by a longlasting afterhyperpolarization. Synchronized, orthodromically evoked burst firing occurred after exposure to penicillin but not to Ba++. Ba++ and penicillin are prototypes of agents which induce epileptogenesis in mammalian cortical neurons by two different but probably interrelated mechanisms. Ba++ causes burst generation by disrupting a delicate balance between depolarizing Ca++ potentials and repolarizing, hyperpolarizing K+ potentials. Penicillin does not affect Ca++- or K+-mediated membrane events; other data suggest that it produces burst generation in hippocampal pyramidal neurons by attenuating gamma-aminobutyric acid-mediated synaptic inhibition, which in turn ordinarily limits intrinsic bursting.

Action Potentials↗
PubMed1980

Extracellular calcium and potassium changes in hippocampal slices.

Ca2+ and K+ ion sensitive microelectrodes were used to measure changes in ionic activities in the CA1 region of hippocampal slices during orthodromic (stratum radiatum) stimulation. Baseline levels of [K+]o and [Ca2+]o were those of the bathing medium which contained 5 mM K+ and 2.0 mM Ca2+. During stimulation [K+]o rose to maximal levels of 12 mM while [Ca2+]o decreased to as low as 1.4 mM. Systematic alterations in extracellular field potentials in stratum pyramidale accompanied the ionic shifts. Following stimulation K+ undershoots occurred. An active K+ uptake mechanism was demonstrated using iontophoretic K+ pulses. [K+]o and [Ca2+]o changes occurred in parallel and in a laminar distribution with maximal changes recorded in stratum pyramidale. Maximal [K+]o changes occurred from baselines of 5 mM and declined progressively at higher baseline levels. During epileptiform activity produced by exposure of slices to penicillin, larger ionic shifts with a more rapid onset occurred. The alterations in [K+]o and [Ca2+]o in the hippocampal slice are similar in some respects to those obtained by stimulation in vivo, making this preparation a potentially useful one for determination of mechanisms and effects of alterations in the ionic microenvironment.

Animals↗
PubMed1980

Effects of TEA on hippocampal neurons.

The effects of the potassium channel blockers, tetraethylammonium (TEA) and tetramethylammonium (TMA) on behavior of hippocampal CA1 neurons were studied in the in vitro slice preparation. Intracellular injections of TEA produced marked spike broadening, increased input resistance, and a prolongation of a putative slow calcium-activated afterhyperpolization (AHP). Little effect was seen on synaptic potentials. Bursting activity induced by TEA in hippocampal neurons was qualitatively different from the epileptiform bursting induced by raising extracellular potassium concentrations or by including penicillin in the bathing medium. Effects of TMA were qualitatively similar to those of TEA, but much slower and less dramatic. The results suggested that there were at least two different potassium channels in the membranes of hippocampal CA1 neurons, and that both were important in determining normal neuronal activity. TEA appeared to preferentially block a fast, voltage-dependent potassium conductance (gk); however, it also modified the slow, calcium-activated gk. Although cell bursting activity may have resulted from blockade of a gk produced by TEA treatment, the epileptiform bursts produced by penicillin exposure appeared to be independent of this mechanism.

Animals↗
PubMed1980

Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity.

The effects of the epileptogenic agent, penicillin, on excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were studied in the hippocampal in vitro slice preparation. The actions of penicillin were compared to those of bicuculline, an antagonist of gamma-aminobutyric acid. Neither substance enhanced monosynaptic EPSP amplitude in CA1 pyramidal cells, but both penicillin and bicuculline depressed IPSPs. Large depolarizations that gave rise to cellular bursting activity did develop after addition of penicillin or bicuculline to the bathing medium. There was also an increase in the incidence of fast prepotentials of 'd-spikes.' These observations are interpreted according to the hypothesis that penicillin and bicuculline block cellular IPSPs, and consequently allow remote intrinsic excitatory events to invade the cell soma and trigger action potentials.

Animals↗
PubMed1980

A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons.

1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.

Action Potentials↗
PubMed1979

Dendritic mechanisms underlying penicillin-induced epileptiform activity.

The action of penicillin on synaptically evoked dendritic activity was examined with the use of hippocampal slice preparations. Orthodormic activation of CA1 pyramidal neurons produced an excitatory-inhibitory postsynaptic potential sequence recorded intracellularly in the dendrites. Treatment with penicillin resulted in the appearance of spontaneous and synaptically evoked multipeaked field potentials and associated depolarization shifts and spike burst generation in CA1 cells. Intracellular recordings revealed that penicillin produced no detectable change in passive membrane properties of the postsynaptic dendrites. However, the inhibitory postsynaptic potential was suppressed by penicillin, resulting in the release of intrinsic dendritic burst firing during synaptic activation. These findings emphasize the role of normal patterns of dendritic burst generation in the production of intense neuronal discharge during penicillin-induced epileptiform activities.

Action Potentials↗
PubMed1979

Intradendritic recordings from hippocampal neurons.

Dendritic activity in guinea pig hippocampal CA1 and CA3 pyramidal neurons was examined by using an in vitro preparation. Histologically confirmed intradendritic recordings showed that dendrites had an average input resistance of 47.0 M omega and average membrane time constant of 33.3 msec. Active spike responses could be evoked by intracellular injection of outward current or by the activation of synaptic inputs. The predominant activity was burst firing. A typical intracellularly recorded dendritic burst consisted o spikes on a slowly increasing depolarizing potential. The spike components of the burst were of two distinct types: low threshold, fast spikes; and high threshold, slow spikes. Tetrodotoxin (1 microgram/ml) blocked the fast spikes, but slow spikes could still be evoked with direct intracellular stimulation. In contrast to dendritic responses, direct depolarization of CA1 somata did not give rise to burst generation. Orthodromic stimuli evoked large-amplitude excitatory postsynaptic potentials, followed by inhibitory postsynaptic potentials in dendrites of CA1 and CA3 neurons. In two instances, simultaneous recordings were obtained from coupled pairs of elements that were presumed to be soma and dendrite of the same CA3 pyramidal neuron. Depolarization of either element led to burst generation at that site, and the underlying slow depolarization appeared to evoke a burst at the other site. This potential postsynaptic amplifying mecahnism was not ordinarily functional because even suprathreshold orthodromic activation did not normally evoke bursting in dendrites.

Action Potentials↗
PubMed1979

Anomalous inward rectification in hippocampal neurons.

1. Anomalous rectification occurred in 54 of 56 hippocampal CA1 neurons studied in vitro. This phenomenon is characterized by a progressive increase in input resistance with membrane depolarization. An average increase in membrane resistance of 45% occurred over a 15-mV region of membrane potential immediately subthreshold to cellular firing. 2. Both Mn2+, a Ca+ antagonist, and tetrodotoxin (TTX), a neurotoxin that blocks regenerative Na+ currents, eliminated anomalous rectification. Ba2+, which can both contribute to intracellular cation influx as well as reduce K+ conductance, increased the magnitude of anomalous rectification. The observations are indirect evidence indicating that a Ca2+-Na+ current may produce the inward-going rectification. 3. Enhancement of anomalous rectification by Ba2+ was associated with the onset of membrane oscillations and spontaneous bursts of repetitive discharges. The magnitude of anomalous rectification may be one factor that predisposes some cortical neurons to bursting behavior.

Animals↗
PubMed1978

Cellular and field potential properties of epileptogenic hippocampal slices.

Epileptogenic activity was induced in hippocampal slices by addition of penicillin (2.0mM) to the bathing medium. Field potential epileptiform events were recorded and single cell bursts studied with intracellular electrodes. Epileptogenic activity was seen in areas CA1 and CA3 of the slice, with bursts in CA3 always leading CA1 bursts; a cut between CA1 and CA3 abolished spontaneous bursting in CA1 but not in CA3. Increased (Mg2+) and decreased (Ca2+) abolished epileptiform discharge, thus demonstrating its dependence on synaptic activity; burst occurrence was also sensitive to (K+). Measurements of single cell resting potentials, resistance, and time constant in CA1 cells revealed no difference between cells in normal medium and cells made epileptogenic by penicillin. Depolarization shifts in CA1 neurons during epileptogenesis did not behave like 'giant EPSPs' but rather were complexes to which depolarizing spike after-potentials, fast prepotentials, and underlying slow depolarizing events all contributed.

Action Potentials↗