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D A Prince

Publications and source records attributed to D A Prince.

At least 109 records · Page 6Linked to original sources
PubMed1984

Synaptic control of excitability in isolated dendrites of hippocampal neurons.

The apical dendrites of CA1 pyramidal cells were isolated from their cell bodies by making cuts through proximal stratum radiatum of transverse hippocampal slices from the guinea pig. This lesion separated the distal apical dendritic elements from the somata, basal dendrites, and 50 to 100 microns of the proximal apical dendritic tree. Orthodromic stimuli in stratum radiatum evoked excitatory synaptic responses in isolated dendrites, but no phasic inhibitory components could be detected. In spite of this surgically produced disinhibition, orthodromic stimuli did not elicit burst activity at the resting membrane potential. However, isolated dendrites and intact dendrites could generate multiple slow spike activity when directly stimulated with depolarizing current pulses. When isolated dendrites were depolarized by DC current, excitatory postsynaptic potentials could evoke subthreshold intrinsic slow depolarizations, or repetitive slow spikes, similar to responses elicited by depolarizing current pulses alone. After exposure to bicuculline (5 microns), both intact and isolated dendrites generated bursts of activity following synaptic activation. A possible mechanism for this action of bicuculline is blockade of a residual GABA-mediated inhibition which was not expressed as a postsynaptic hyperpolarization in isolated dendrites. This bicuculline-sensitive event was capable of depressing dendritic excitability in the absence of the recurrent inhibitory synaptic input and was very effective in controlling burst activity. Our results indicate that the dendritic electrical behavior is dependent on a complex interaction between synaptic and voltage-sensitive events.

Afferent Pathways↗
PubMed1983

Cholinergic enhancement of penicillin-induced epileptiform discharges in pyramidal neurons of the guinea pig hippocampus.

Acetylcholine (1-20 mM) was applied to guinea pig hippocampal slices bathed in normal and penicillin-containing media. Recordings in the CA 1 pyramidal cell layer in the presence of penicillin showed that acetylcholine caused a prolonged enhancement of the extracellular field potential. Intracellular recordings documented an increase in duration of cell bursting, a decrease in burst afterhyperpolarization, and a membrane depolarization lasting 1-5 min. These results suggest that the actions of acetylcholine to increase membrane excitability interact with penicillin-induced disinhibition to enhance hippocampal epileptogenesis.

Acetylcholine↗
PubMed1983

Coupling between neurons of the developing rat neocortex.

We have estimated the prevalence of coupling between neurons of the rat neocortex during postnatal development. Single intracellular injections of the fluorescent dye Lucifer Yellow CH resulted in dye coupling among 70% of neurons from 1 to 4 days of age. Dye coupling dropped to 30 to 40% by 10 to 18 days and occurred in 20% of injected adult neurons. The number of neurons per dye-coupled aggregate also decreased. Whereas three to seven coupled neurons were common in cortex of 1 to 4 days, aggregates of more than two neurons were exceptionally rare in adults. The frequency of dye coupling did not vary systematically with cortical depth at any age. When chemical synaptic activity was blocked, most 4-day neurons exhibited short latency antidromically evoked depolarizations which were relatively insensitive to repetitive activation and membrane polarization. These depolarizations may represent electrotonically conducted spikes from coupled neurons. No such potentials were found in adult neurons. The results suggest that neuronal coupling is extensive in immature rat neocortex, but that coupling declines at a time just before the numbers of chemical synapses increase most rapidly.

Aging↗
PubMed1983

Mechanisms of epileptogenesis in brain-slice model systems.

Studies of the mechanisms of epileptogenesis in brain-slice model systems have indicated that there are three underlying processes which interact with one another and lead to the development of interictal discharge. These include (a) intrinsic burst activity, (b) disinhibition, and (c) excitatory synaptic coupling. Intrinsic membrane excitability may be altered by neuromodulators, injury, genetic, and other factors. Disinhibition in effect releases intrinsic burst generating capacities in populations of neurons, and may become an important factor following cortical injury or repetitive activation of inhibitory circuits. Excitatory synaptic coupling is required for evoking intrinsic burst discharges, and also to synchronize populations of neurons. EPSPs also serve as one of the generators for slow depolarization shifts. The contribution of each of these factors to epileptogenesis presumably varies with a type of pathological process and the properties of the involved neuronal population.

Action Potentials↗
PubMed1982

Enkephalin inhibition of inhibitory input to CA1 and CA3 pyramidal neurons in the hippocampus.

Enkephalin-induced excitation in the hippocampus has been attributed to the attenuation of inhibitory input as well as to augmentation of excitatory input to pyramidal neurons. We have further examined these possible mechanisms of enkephalin action, as well as the possibility that enkephalins may be affecting intrinsic membrane properties, by recording intracellularly from CA1 and CA3 pyramidal cells in the guinea pig hippocampal brain slice preparation. It was observed that the inhibitory synaptic potential was significantly decreased in the presence of leucine enkephalin and D-alanine, D-leucine-enkephalin (DADL), whereas the excitatory synaptic potential, revealed by block of the inhibitory postsynaptic potential (IPSP) by bicuculline, was unaltered. In addition, the response of pyramidal cells to pressure-applied GABA was unaffected by enkephalin, as were the voltage-dependent membrane conductances. The increase in excitability which was observed in both field potential and intracellular recordings to drop application of DADL must, then, be due to a purely presynaptic block of inhibitory interneurons in both the CA1 and CA3 areas of the hippocampus.

Animals↗
PubMed1982

Cholinergic excitation of mammalian hippocampal pyramidal cells.

Responses of CA1 pyramidal neurons to ACh were recorded with intracellular microelectrodes utilizing the in vitro guinea pig hippocampal slice preparation. ACh was delivered by drop or iontophoretic application to stratum oriens or stratum radiatum. Threshold dose for drop application was 1 mM. An initial hyperpolarization of 3.1 +/- 1.8 (S.D.) mV associated with a decrease in membrane input resistance (RN) of 21 +/- 9% (S.D.) occurred in about half the cells. This result is consistent with a presynaptic action of ACh mediated through excitation of inhibitory interneurons. This interpretation was supported by recordings of cholinergic excitatory responses from presumed interneurons, and repetitive spontaneous IPSPs from pyramidal neurons during the hyperpolarization. ACh evoked a slow depolarization (14.3 +/- 10.8 (S.D.) mV) accompanied by a peak increase in apparent input resistance (Ra) of about 60% in the majority of cells. Large increases in spike frequency were associated with these events but action potential shape was unchanged. Plots of Ra versus membrane potential following ACh application revealed that Ra increases were proportionately higher at depolarized membrane potential levels (less than or equal to -70 mV) in some neurons. In these cells Ra was increased significantly at -60 mV (28%), but only 6% at -75 mV. These results are consistent with the conclusion that ACh reduces a voltage-dependent gK, distinct from delayed rectification. ACh also induced a non-voltage-dependent increase in Ra in some cells. ACh-evoked changes in Ra were long-lasting and gave rise to alterations in firing mode, with development of burst generation. ACh also transiently blocked after hyperpolarizations which followed spike trains in pyramidal neurons and presumed interneurons, an action which may be related to effects on a Ca2+-activated gK.

Acetylcholine↗
PubMed1982

Ionic mechanisms of cholinergic excitation in mammalian hippocampal pyramidal cells.

Intracellular recordings from CA1 hippocampal pyramidal neurons were obtained using the in vitro hippocampal slice preparation. Responses to ACh were monitored in the presence of blockers of voltage-dependent conductances including Mn2+, TTX and Ba2+. When Mn2+ was used to block voltage-dependent Ca conductance and possible indirect presynaptic cholinergic actions, ACh still induced a significant voltage-sensitive increase in apparent input resistance (Ra) (29%), but only an insignificant depolarization of membrane potential (Vm). When both voltage-dependent Ca and Na conductances were blocked by application of Mn2+ and TTX, respectively, ACh produced voltage-dependent increases in Ra (31%) without significant depolarization. In solutions containing TTX alone, ACh produced voltage-sensitive increases in Ra (32%) as well as a significant depolarization (6.2 +/- 3.1 mV (S.D.)). ACh transiently blocked the conductance increase which followed presumed Ca spikes, suggesting an action on the Ca-activated K-dependent conductance. The effects of Ba2+ application (100-200 microM) on Ra mimicked those of ACh. When ACh was applied to neurons in the presence of Ba2+, Ra remained unchanged, although Vm depolarization of 5-15 mV was still seen. The data indicate that ACh decreases both a voltage-dependent K conductance (distinct from that of the delayed rectifier) and a Ca-activated K conductance. Muscarinic cholinergic depolarization occurs as a result of blockade of K conductance, and is mediated by voltage-dependent Ca and Na conductances, and perhaps by presynaptic actions.

Acetylcholine↗
PubMed1982

Variations in electrophysiological properties of hippocampal neurons in different subfields.

Intracellular recordings were made from hippocampal pyramidal cells (HPCs) in subregions CA1a, b, c, CA2 and CA3a, b of the guinea pig hippocampal slice. There were significant differences in the mode of spike discharge at various sites. Most neurons in CA1b and CA3b fired single spikes spontaneously, or during intracellular depolarizing current pulses. HPCs in the CA1a and c, as well as CA2 and CA3a subregions usually had a burst mode of discharge under the same conditions. Basic differences in neuronal properties presumably underlie these varieties of behavior between or within various regions. Specification of the site or subregion of recording is important especially in those experiments where the mode of spike discharge or membrane events in HPCs are important variables.

Animals↗
PubMed1982

Cholinergic pharmacology of mammalian hippocampal pyramidal cells.

Responses of CAl pyramidal cells to cholinergic compounds were recorded with intracellular microelectrodes in guinea-pig hippocampal slices. Perfusion of slices with medium containing the muscarinic antagonists atropine or scopolamine (10(-7)-10(-6)M) blocked all actions of acetylcholine. Properties of control neurons and those from separate populations of neurons impaled in slices exposed to muscarinic blocking agents were compared. 1-2 h of perfusion with atropine-containing media significantly decreased membrane input resistance from 37.6 +/- 8.7 (S.D.) M omega (n = 74) to 21.9 +/- 7.7 (S.D.) M omega (n = 24) without producing significant changes in membrane potential. Muscarinic antagonists also reduced or eliminated the anomalous inward rectification normally seen in hippocampal pyramidal neurons. Exposure of slices to 10(-5)-10(-6)M eserine for about 1 h produced changes in neuronal membrane input resistance and potential and slow after hyperpolarizations similar to those elicited by application of acetylcholine. Bethanechol mimicked the actions of acetylcholine but was effective at lower concentrations and had longer lasting effects on afterhyperpolarizations. Nicotine produced an excitatory response in only one of 7 neurons. These experiments demonstrate that the actions of acetylcholine on hippocampal CAl neurons result from interaction with muscarinic receptors. Acetylcholine has modulatory effects on cell membrane properties which may be mediated through tonic release mechanisms.

Acetylcholine↗
PubMed1982

Electrophysiological properties of neocortical neurons in vitro.

1. Intracellular recordings were obtained from neurons of the guinea pig sensorimotor cortical slice maintained in vitro. Under control recording conditions input resistances, time constants, and spiking characteristics of slice neurons were well within the ranges reported by other investigators for neocortical neurons in situ. However, resting potentials (mean of -75 mV) and spike amplitudes (mean of 93.5 mV) were 10-25 mV greater than has been observed in intact preparations. 2. Current-voltage relationships obtained under current clamp revealed a spectrum of membrane-rectifying properties at potentials that were subthreshold for spike generation. Ionic and pharmacologic analyses suggest that subthreshold membrane behavior is dominated by voltage-sensitive, very slowly inactivating conductances to K+ and Na+. 3. Action potentials were predominantly Na+ dependent under normal conditions but when outward K+ currents were reduced pharmacologically, it was possible, in most cells, to evoke a non-Na+-dependent, tetrodotoxin-(TTX) insensitive spike, which was followed by a prominent depolarizing after-potential. Both of these events were blocked by the Ca2+ current antagonists, Co2+ and Mn2+. 4. A small population of neurons generated intrinsic, all-or-none burst potentials when depolarized with current pulses or by synaptic activation. These cells were located at a narrow range of depths comprising layer IV and the more superficial parts of layer V. 5. Spontaneous excitatory synaptic potentials appeared in all neurons. Spontaneous inhibitory events were visible in only about 10% of the cells, and in those cases apparently reversed polarity at a level slightly positive to resting potential. Stimulation of the surface of the slice at low intensities evoked robust and usually concurrent excitatory and inhibitory synaptic potentials. Unitary inhibitory postsynaptic potentials (IPSPs) reversed at levels positive to rest. Stronger stimulation produced a labile, long-duration, hyperpolarizing IPSP with a reversal potential 15-20 mV negative to the resting level. 6. Neocortical neurons in vitro retain the basic membrane and synaptic properties ascribed to them in situ. However, the array of passive and active membrane behavior observed in the slice suggests that cortical neurons may be differentiated by specific functional properties as well as by their extensive morphological diversity.

Action Potentials↗
PubMed1982

Mechanisms of neocortical epileptogenesis in vitro.

1. The cellular mechanisms underlying interictal epileptogenesis have been examined in an in vitro slice preparation of guinea pig neocortex. Penicillin or bicuculline was applied to the tissue, and intracellular recordings were obtained from neurons and glia. 2. Following convulsant application, stimulation could elicit a short-latency excitatory postsynaptic potential (EPSP) and a large, longer latency depolarization shift (DS) in single neurons. DSs in neurons of the slice were very similar to those evoked in neurons of neocortex in vivo in that they displayed an all-or-none character, large shifts in latency during repetitive stimuli, long afterpotentials, and a prolonged refractory period. In contrast to epileptogenesis produced by penicillin in intact cortex, neither spontaneous DSs nor ictal episodes were observed in neocortical slices. 3. In simultaneous recordings from pairs of neurons within the same cortical column, DS generation and latency shifts were invariably synchronous. DS generation in neurons was also coincident with large, paroxysmal increases of extracellular [K+], as indicated by simultaneous recordings from glia. 4. When polarizing currents were applied to neurons injected with the local anesthetic QX-314, the DS amplitude varied monotonically and had an extrapolated reversal potential near 0 mV. In neurons injected with the K+-current blocker Cs+, large displacements of membrane potential were possible, and both the short-latency EPSP and the peak of the DS diminished completely at about 0 mV. At potentials positive to this, the short-latency EPSP was reversed, and the DS was replaced by a paroxysmal hyperpolarization whose rise time and peak latency were prolonged compared to the DS evoked at resting potential. The paroxysmal hyperpolarization probably represents the prolonged activation of the impaled neuron by EPSPs. 5. Voltage-dependent components, including slow spikes, appeared to contribute to generation of the DS at resting potential in Cs+-filled cells, and these components were blocked during large depolarizations. 6. The results suggest that DS generation in single neocortical neurons occurs during synchronous synaptic activation of a large group of cells. DS onset in a given neuron is determined by the timing of a variable-latency excitatory input that differs from the short-latency EPSP. The DS slow envelope appears to be generated by long-duration excitatory synaptic currents and may be modulated by intrinsic voltage-dependent membrane conductances. 7. We present a hypothesis for the initiation of the DS, based on the anatomical and physiological organization of the intrinsic neocortical circuits.

Animals↗
PubMed1982

Effects of local anesthetic QX-314 on the membrane properties of hippocampal pyramidal neurons.

The quaternary lidocaine derivative QX-314 was applied internally to CA1 pyramidal neurons of the guinea-pig hippocampal slice preparation. This local anesthetic blocked both fast, Na+-dependent action potentials and the voltage-dependent, non-inactivating Na+ conductance. Partially blocked Na+ spikes exhibited pronounced frequency-dependent depression at rates as low as 0.2 Hz. Ca++-dependent electrogenesis, synaptic potentials and glutamate-induced depolarizations were apparently unaffected even after large doses of QX-314. The results indicate that the cellular mechanisms of local anesthetics on central neuronal membranes are similar to those described for peripheral axons. The frequency-dependence of spike blockade may account for some of the effects of local anesthetics on the central nervous system in vivo. Additionally, the localized intracellular application of QX-314 may prove useful as a specific pharmacological tool in studies of central neurons.

Action Potentials↗
PubMed1982

Dopamine action on hippocampal pyramidal cells.

Dopamine (DA) was applied to CA1 region pyramidal cells in slices of guinea pig hippocampus maintained in vitro in order to examine its electrophysiological effect on CNS neurons. DA induced hyperpolarization of membrane potential and an increased conductance in 75% the 21 CA1 neurons to which it was applied. DA also augmented the afterhyperpolarizations and increased conductance which normally follow spike trains in these neurons. These effects were not altered by intracellular injections of Cl- but were blocked when slices were bathed in Mn2+ solutions. The Mn2+ blockade of DA-induced hyperpolarizations could be overcome when large amounts of agonists were applied. The DA effects were long lasting, were mimicked by the dopamine agonists apomorphine and Epinine, and were blocked by the dopamine antagonists flupenthixol and chlorpromazine. Extracellular or intracellular application of cyclic AMP mimicked the effects of DA. The results suggest that DA-induced hyperpolarization and conductance changes are mediated by a Ca2+-activated K+ conductance. DA may increase the intracellular Ca2+ concentration through effects on one of the Ca2+ buffering mechanisms. The long duration of these effects suggest that DA works though some intracellular intermediary, perhaps cyclic AMP, considering that the actions of cyclic AMP on membrane properties are similar to those of DA. The dopaminergic projection to the hippocampus should have a powerful inhibitory action, which would be most effective in modulating the activities of neurons exhibiting high levels of excitability, particularly cells involved in cyclical burst generation.

Action Potentials↗
PubMed1982

Electrophysiology of isolated hippocampal pyramidal dendrites.

In order to study the electrical properties of dendritic membranes independent of the effects of somatic potentials, intracellular recordings in guinea pig hippocampal slices were obtained from the dendrites of CA1 pyramidal neurons (HPCs) which had been isolated from their somata by cuts made through the proximal stratum radiatum. Spikes and subthreshold membrane responses to intracellular current pulses were compared in intact and isolated dendrites and in the residual portions of neurons whose apical dendrites had been severed ("isolated somata"). Isolated dendrites generated both fast, QX-314-sensitive, sodium-mediated spikes, and slow higher threshold spikes which were QX-314-resistant and presumably mediated by Ca2+. Depolarization of "isolated somata" ordinarily evoked only fast (Na+) spikes, but presumed Ca2+ spikes could be elicited after exposure to QX-314 (a local anesthetic). Anomalous inward rectification was depressed by QX-314 in somata but not in dendrites, suggesting that the ionic basis for subthreshold as well as regenerative conductances was different at different sites on the neuron. The dendritic membrane in CA2 HPCs thus generates both Na+- and CA2+-mediated spike potentials and a subthreshold response which probably is mediated primarily by CA2+. Attempts to describe the integrative functions of these neurons must take into account the variety of conductances which are activated nonuniformly in somata and dendrites by changes in membrane potential.

Action Potentials↗
PubMed1981

Acetylcholine induced modulation of hippocampal pyramidal neurons.

Applications of acetylcholine to hippocampal slices maintained in vitro resulted in slow depolarizations and simultaneous increases in membrane resistance (RN)in hippocampal pyramidal neurons. Increases in RN had both voltage dependent and voltage independent components. These effects were associated with increases in cell discharge frequency, and development of spontaneous as well as synaptically and directly evoked burst discharges. The increase in RN and burst firing lasted for hours. Muscarinic antagonists blocked these actions and in addition, produced a decrease in membrane resistance, which appeared to be due to blockade of a tonic effect of acetylcholine on postsynaptic membrane properties. These findings suggest that ACh acts as a neuromodulator in the hippocampus.

Acetylcholine↗