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Biomedical subjects

W C Abraham

Publications and source records attributed to W C Abraham.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of the NMDA receptor/channel antagonists CPP and MK801 on hippocampal field potentials and long-term potentiation in anesthetized rats.

The effects of the competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, 3-[(+/- )-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK801) were tested on hippocampal field potentials and long-term potentiation (LTP) in urethane-anesthetized rats. Neither drug had any significant effects on the dentate hilar population excitatory postsynaptic potential (EPSP) evoked by perforant path stimulation 30 or 150 min postinjection. However, both drugs produced a dose-dependent decrease in population spike amplitude at these times. Both drugs (at the highest doses) also blocked LTP when induced 150 min after administration, and this was related to a smaller response evoked during tetanization. CPP exerted similar effects on commissural-CA1 evoked responses and LTP. CPP remained an effective blocker of LTP for 6-8 h, and was still partially effective after 20-24 h. MK801 washed out more rapidly. The effect of MK801 on LTP did not depend on stimulus-evoked transmitter release during the pretetanization period. The results indicate that both CPP and MK801 have potent effects on LTP in the in vivo preparation, but that this is accompanied by an independent effect on evoked cell discharge.

Action Potentials↗
PubMed1988

Effects of the NMDA antagonist 2AP5 on complex spike discharge by hippocampal pyramidal cells.

The N-methyl-D-aspartate receptor antagonist D,L-2-amino-5-phosphonopentanoate (2AP5) was administered intraventricularly to determine its effect on the complex spike firing pattern of spontaneously active hippocampal pyramidal cells recorded in urethane anaesthetized rats. Following 2AP5 delivery, complex spike firing decreased by a mean 36%, while only a 5% decrease was observed after saline injection. This effect could not be explained by changes in firing rate per se but appeared to be related to the degree of blockade of commissurally induced long-term potentiation. Thus 2AP5 not only disrupts synaptic plasticity in the hippocampus but can also alter the pattern of ongoing activity of the pyramidal cells.

2-Amino-5-phosphonovalerate↗
PubMed1987

Field potential evidence for long-term potentiation of feed-forward inhibition in the rat dentate gyrus.

Trains of high-frequency stimulation to the perforant path cause (i) long-term potentiation (LTP) of the population excitatory post-synaptic potential (EPSP), (ii) a lasting increase in the population spike, and (iii) a lasting alteration of the relationship between the EPSP and population spike (E-S relationship), consisting of a decreased x-intercept and decreased slope of the linear regression. To compare the thresholds of these changes, we applied a series of trains, increasing in duration from below LTP threshold. The EPSP potentiated with about the same low threshold as the reduction in E-S slope, whereas the reduction in E-S x-intercept required longer trains. In the second experiment, LTP of the EPSP was reduced by concurrent high-frequency stimulation of the commissural input and a lasting reduction of the population spike height was observed. In a third experiment, picrotoxin, an antagonist of gamma-aminobutyric acid (GABA)-mediated inhibition, blocked the decrease in slope of the E-S relationship which normally accompanies LTP. These results imply that perforant path/granule cell LTP is normally accompanied by long-term potentiation of a feed-forward inhibitory pathway which may involve interneurones.

Animals↗
PubMed1987

Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus.

1. Tetanization of hippocampal pyramidal cell afferents travelling in stratum radiatum of area CA1 induces both long-term potentiation (l.t.p.) of extracellularly recorded excitatory postsynaptic potentials (e.p.s.p.s), and an increase in the number of cells firing, as measured by the extracellular population spike, for a given sized field e.p.s.p. The mechanism of this latter change, known as e.p.s.p.-spike (E-S) potentiation, was investigated in the guinea-pig hippocampal slice preparation. 2. Plots of the E-S relation before and after tetanization were constructed from measures taken over a series of stimulus strengths. Tetanization of afferents in stratum radiatum decreased the spike threshold by 24%, while the gamma-aminobutyric acid antagonist picrotoxin (PTX) decreased spike threshold by 72%. Sequential administration of PTX and tetanization, in either order, resulted in no more change in the E-S threshold than did PTX application alone. 3. Extracellular synaptic potentials, matched for initial slope before and after tetanization by adjusting the stimulus strength, showed an increased peak amplitude and increased peak latency following tetanization. PTX produced similar but larger percentage changes. Tetanization in the presence of PTX, however, did not alter the field potential wave shape. 4. Intracellular postsynaptic potentials (p.s.p.s) were also matched for initial slope before and after tetanization. Tetanization induced p.s.p. shape changes similar to those observed extracellularly, i.e. in the direction of less inhibition. Such changes did not occur in the presence of PTX. 5. Inhibitory p.s.p.s (i.p.s.p.s) were studied in depolarized pyramidal cells with microelectrodes filled with QX-314. Tetanization of afferents in stratum radiatum produced i.p.s.p. increases in eight of nineteen cells. These increases were generally attributable to an increased activity in the recurrent inhibitory pathway. Tetanization of the alveus failed to produce any lasting increases in the i.p.s.p. amplitude. 6. Tetanization of afferents in stratum radiatum decreased the ratio of the intracellular i.p.s.p. to field e.p.s.p. over stimulus strengths below population spike threshold. Above population spike threshold, the ratio tended towards its pretetanization level. 7. The results indicate that E-S potentiation results from an increase in the level of depolarization reached by a synaptic potential of given initial slope. These findings support the hypothesis that tetanization induces greater l.t.p. of excitatory inputs onto pyramidal cells than of inputs onto feed-forward inhibitory interneurones.

Action Potentials↗
PubMed1987

Long-term potentiation in the hippocampus using depolarizing current pulses as the conditioning stimulus to single volley synaptic potentials.

The conditions responsible for the associative properties of long-term potentiation (LTP) were examined in the CA1 region of the hippocampal slice preparation. Intracellularly recorded EPSPs resulting from single-volley stimulation at low frequency (0.15-0.1 Hz) in the stratum radiatum or oriens were paired with depolarizing current pulses (50-100 msec) injected through the recording microelectrode. It is shown that these EPSPs, when paired with pulses of sufficient magnitude, become potentiated. This potentiation generally reached a peak after 20-30 pairing events and could outlast the conditioning period by more than 1 hr. It was specific to the paired input, was blocked by 2-amino-5-phosphonovalerate (APV) and was largely blocked by prior homosynaptic tetanization (and vice versa). In experiments performed with picrotoxin (PTX) in the bath, EPSPs were potentiated using 2-4 nA current pulses, with somewhat higher values in normal solution. The effective current pulses, in both normal and PTX solution, produced a repetitive spike discharge of 7-11 spikes (per 100 msec), and within this range, higher frequencies were associated with larger potentiations. However, since similar degrees of EPSP potentiation were observed following blockade of spike activity by intracellular QX-314, spike activity was not the primary conditioning factor. For the potentiation to appear, the EPSP had to occur together with the current pulse or precede it by less than about 100 msec. No potentiation was observed when the EPSP immediately succeeded the pulse. The results suggest that the cooperativity aspect of LTP is related to a need for sufficient postsynaptic depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1986

Single high strength afferent volleys can produce long-term potentiation in the hippocampus in vitro.

Although hippocampal long-term potentiation (LTP) is normally elicited by tetanization of an afferent input, it may also be induced by pairing afferent volleys with strong depolarizing conditioning stimuli. In extracellular recordings made from area CA1 of hippocampal slices bathed with a picrotoxin-containing solution, long-lasting potentiation was produced by high strength single volleys alone. Potentiation occurred with intervals between high strength stimuli as great as one per minute. Tetanization-induced LTP was no greater than tetanization-induced LTP plus high strength single volley potentiation, given in either order. These data suggest that single afferent volleys can induce LTP under conditions of reduced inhibition.

Action Potentials↗
PubMed1985

An analysis of the increase in granule cell excitability accompanying habituation in the dentate gyrus of the anesthetized rat.

Repeated low-frequency stimulation of the perforant path results in a decrement in the population EPSP and population spike recorded in the hilus of the dentate gyrus. The EPSP decrement is accompanied, however, by an increase in the population spike height/population EPSP slope relation, suggesting that an increase in granule cell excitability also occurs. The present experiments explored the mechanisms of this apparent increase in excitability using standard field potential recording techniques to assess perforant path input/output curves in rats anesthetized with sodium pentobarbital. Low-frequency homosynaptic stimulation (512 pulses, 1 Hz) of the perforant path resulted in a decreased spike threshold and overall shift to the left of the function relating population spike height to EPSP slope. These changes were consistently produced, even when granule cell discharge was inhibited by conditioning stimulation of the contralateral hilus. On the other hand, low-frequency heterosynaptic (lateral perforant path) or antidromic (mossy fiber) driving of the granule cells only slightly increased the medial path spike/EPSP relation, and did not alter the spike threshold. The excitability shift accompanying habituation was qualitatively different from that associated with long-term potentiation, but these shifts did not summate. The interpretation which best explains these various results is that granule cell excitability is increased during low-frequency perforant path stimulation by a process of disinhibition, caused by habituation of perforant path excitatory synaptic drive onto feed-forward inhibitory interneurons.

Animals↗
PubMed1985

Heterosynaptic changes accompany long-term but not short-term potentiation of the perforant path in the anaesthetized rat.

Brief high-frequency trains of electrical stimulation delivered to the perforant path result in long-term potentiation (l.t.p.) of field potentials recorded extracellularly from granule cells of the dentate gyrus. L.t.p. of the population spike is often disproportionately greater than l.t.p. of the population excitatory post-synaptic potential (e.p.s.p.). We have investigated the basis of this effect in rats anaesthetized with sodium pentobarbitone. A series of graded stimuli were given before and after tetanization of the perforant path. From data obtained in this way, we plotted stimulus-response curves, and the relation (E-S curve) between the slope of the population e.p.s.p. (E) and the amplitude of the population spike (S). Curves relating spike onset latency to the slope of the e.p.s.p. were also constructed. Tetanization of the combined medial and lateral components of the perforant path led to long-term changes in the relation between the e.p.s.p. and the population spike. For a given e.p.s.p., the corresponding population spike was of greater amplitude and earlier onset. This E-S potentiation was marked by a shift to the left of the E-S amplitude curve and a downward displacement of the E-S latency curve. Tetanization of the lateral component of the perforant path had two long-term effects on responses evoked by test stimuli to the untetanized medial component: (1) long-term depression of the medial e.p.s.p. and (2) long-term E-S potentiation. The net result of these two heterosynaptically induced effects was to leave unaltered information transfer across medial perforant path-granule cell synapses; for a given test volley the e.p.s.p. was smaller, but because of E-S potentiation the population spike remained relatively unaffected. Short-term potentiation, which has a time course of only a few minutes and is presumed to be mediated by presynaptic mechanisms, was not accompanied by E-S potentiation or by corresponding changes in spike latency. Possible mechanisms of long-term heterosynaptic depression of the e.p.s.p. and of homo- and heterosynaptic E-S potentiation, are discussed. We conclude that although these effects probably reflect a generalized post-synaptic change, this change is unlikely to be a prolonged reduction in the membrane potential of granule cells.

Action Potentials↗
PubMed1984

Differences in synaptic transmission between medial and lateral components of the perforant path.

The differences between the potentials recorded in the hilus of the dentate gyrus following test shocks applied separately to the medial perforant path (MPP) and the lateral perforant path (LPP) have been ascribed to the greater length of dendrite over which the LPP potentials are electrotonically conducted to the somata of the granule cells. We tested this hypothesis by recording MPP and LPP evoked potentials in the hilus and in the molecular layer of both in vivo and in vitro preparations. Analysis of field potential and current source density depth profiles in vivo indicated that different waveshapes occurred not only in the hilus but at the sites of synaptic contact in the molecular layer as well. In the in vitro study, paired stimulating and recording electrodes were stepped through the molecular layer and revealed a relatively sudden waveshape change around 225 micron from the cell layer, where the transitional zone between MPP and LPP terminal fields was expected to be located. Quantitative analysis of the differences between the potentials recorded in the molecular layer and the hilus revealed that electrotonic decay accounts for approximately 20% of the difference seen in the hilus between the MPP and LPP potentials. Our data therefore suggest that the differences between MPP and LPP hilar potentials are due mostly to differences between the two pathways in their properties of synaptic transmission and are due relatively little to the different sites of synaptic contact on the dendritic tree.

Animals↗
PubMed1984

Chronic ethanol-induced decreases in the response of dentate granule cells to perforant path input in the rat.

The neurotoxic effects of chronic ethanol consumption were investigated in the rat hippocampus by electrophysiological analyses of synaptic function of entorhinal afferents to stratum moleculare of the dentate gyrus. Rats were maintained on ethanol- or sucrose-containing liquid diets for a period of 20 weeks and were withdrawn from the special diets for a period of 8 weeks prior to acute electrophysiological studies. Synaptic response strength (Input/Output (I/O) functions) and synaptic potentiation (paired-pulse, frequency and long-term) were evaluated in each rat. Chronic ethanol treatment failed to influence the response strength or potentiation of basic synaptic responses (EPSP). Rather, the ethanol effects were confined to the population spike (PS). Chronic ethanol treatment produced reductions in PS responses 1) in the asymptotic portions of the I/O curves, 2) in paired-pulse potentiation, 3) in response to 1 and 5 Hz low-frequency stimulation and 4) during the development of long-term potentiation. Expressing PS amplitude as a function of EPSP amplitude emphasized the independence of these actions from those of the synaptic potentials. Definitive evidence concerning the cellular alterations underlying these effects of chronic ethanol treatment are presently lacking. However, available evidence supports the hypothesis that the ethanol-induced decreases in PS responses result from a reduction in the "excitability" of granule cells in the dentate gyrus.

Afferent Pathways↗
PubMed1982

Electrophysiological analysis of synaptic distribution in CA1 of rat hippocampus after chronic ethanol exposure.

This study investigated the long-lasting effects of chronic ethanol consumption on the distribution of Schaffer collateral-commissural (SCH/COM) afferents within stratum radiatum of rat hippocampal CA1. Experimental animals were fed an ethanol-containing liquid diet for 20 weeks but were withdrawn from the special diet for at least 8 weeks prior to acute electrophysiological recordings. Field potential laminar analyses were performed by stepping the recording electrode in 25 microns increments through CA1 and sampling evoked potentials at each point. One-dimensional current-source density (CSD) was calculated from the field potential laminar profiles to enhance spatial resolution of current sources and sinks. Stimulation of the SCH/COM afferents elicits short-latency, negative field potentials throughout the synaptic terminal zone (stratum radiatum). CSD analysis in normal animals revealed that the synaptic currents generated in stratum radiatum concentrate into bimodal yet overlapping components, peaking 71.3 microns and 228.3 microns from the pyramidal cell layer. Chronic ethanol treatment produced: (1) a 13.2% shrinkage of the overall extent of current sinks in stratum radiatum; (2) a 37.4% reduction in the spatial extent of the sink proximal to the cell layer; and (3) an increase in the amplitude of the more distal sink. We tentatively propose the proximal and distal sinks to reflect a separation of the COM and SCH afferents, respectively. Chronic ethanol thus appeared to have selectively produced persistent damage to the COM-CA1 pathway.

Action Potentials↗
PubMed1982

An electrophysiological analysis of chronic ethanol neurotoxicity in the dentate gyrus: distribution of entorhinal afferents.

This study investigated the persistent effects of chronic ethanol consumption on the distribution of entorhinal afferents to stratum moleculare of the dentate gyrus. Rats were maintained on ethanol, or sucrose-containing liquid diets, for a period of 20 weeks but were withdrawn from the special diet for at least 8 weeks prior to acute electrophysiologic recordings. One-dimensional laminar analyses were obtained by stepping a microelectrode in 25 microns increments across both the dorsal and ventral blades of the dentate gyrus and sampling the field potentials at each point. Current-source density (CSD) was calculated from the field potential data. Electrical stimulation of the angular bundle elicited a short-latency, negative field potential covering the outer 2/3 of the molecular layer. CSD analysis revealed a major current sink in stratum moleculare bounded by a major current source, localized to the hilus, granule cell layer, and proximal stratum moleculare, and a minor current source localized to the outer molecular layer. Chronic ethanol treatment resulted in (1) a significant shrinkage of the spatial extent of the current sink in stratum moleculare, (2) a significant reduction in the distance from the peak inward synaptic current to the granule cell layer and (3) no change in the distance from the proximal inversion point to the granule cell layer. Taken together, these results indicate a loss of entorhinal afferents in the outer molecular layer. Coupled with available anatomical evidence, these results suggest that chronic ethanol treatment produces a preferential loss of lateral entorhinal afferents to the dentate gyrus.

Afferent Pathways↗
PubMed1981

Augmentation of short-term plasticity in CA1 of rat hippocampus after chronic ethanol treatment.

The neurotoxic effects of chronic ethanol exposure were investigated in rat hippocampus by electrophysiological analysis of the Schaffer collateral-commissural input to stratum radiatum of CA1. Experimental animals were fed an ethanol-containing liquid diet for 20 weeks but were withdrawn from the special diet at least eight weeks prior to acute electrophysiological recordings. Ethanol treatment had no effect on input-output relationships for either the population EPSP or the population spike (PS). During paired-pulse stimulation, the ethanol group exhibited a greater facilitation of the test pulse PS relative to the control group, although potentiation of the EPSP was unchanged. In addition, the ethanol group showed a trend toward greater facilitation of the PS during 5 and 10 Hz tetani. No differences between groups were observed in the magnitude or duration of the long-term potentiation produced by 5, 10 or 100 Hz stimulus trains. Ethanol treatment did significantly reduce the transient spike depression after low frequency stimulation. This pattern of results is similar to that found for treatments which reduce hippocampal recurrent inhibition. Thus, chronic ethanol treatment may produce a lasting disruption of intrinsic inhibitory neurotransmission in the rat hippocampus.

Animals↗
PubMed1981

A longitudinal study of prism adaptation in infants from six to nine months of age.

This study replicated a previous demonstration of prism-induced aftereffects in 5-9-month-old infants. Aftereffects were considered to be changes in direction of reaching for visual targets following prism exposure. The present study employed a longitudinal design. In the experimental group, infants were exposed to 25-diopter lateral displacing prisms once each month from 5 to 9 months. Since many of the subjects were unable to complete testing at 5 months, data for that age level were not included in the main analyses. In a control group, infants were tested each month but were exposed to prisms only at 9 months of age. The magnitude of aftereffects for control subjects at 9 months was not significantly greater than aftereffects obtained for experimentals at 6 months, so there was little evidence of changes in adaptability due to age or repeated exposure to the prisms. The finding of an increase in the frequency of reaching with the left hand during exposure to leftward-deviating prisms was replicated. Such a shift in hand preference probably represents an alternative form of adaptation which for methodological reasons has not been observed in adults. The aftereffect and frequency results were complementary and provide a clear demonstration of adaptation to prismatic displacement between 6 and 9 months.

Adaptation, Physiological↗
PubMed1979

Adaptation to displacing prisms in human infants.

This research reports a first attempt to study adaptation to laterally displacing prisms in human infants of ages six to ten months. Twenty infants were tested over four days under conditions similar to those used in adult adaptation studies. Evidence was found of vigorous adaptation when infants were exposed to base-right prisms under conditions of active exposure. Detailed consideration is given to the conditions and methods of studying adaptation in infants and implications for adult studies.

Adaptation, Psychological↗