Blockade and Disruption of Neocortical Long-term Potentiation Following Electroconvulsive Shock in the Adult, Freely Moving Rat

Christopher Trepel1 and Ronald J. Racine

Department of Psychology, McMaster University, Hamilton, Ontario, Canada L8S 4K1


    Abstract
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 Footnotes
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Although the neocortex has been considered to be highly resistant to the induction of long-term potentiation (LTP), we have recently shown that spaced and repeated stimulation of white matter afferents reliably induces neocortical LTP in the freely moving rat. The following study examined the effects of maximal electroconvulsive shock (MES) stimulation on the induction of LTP in the chronically prepared rat. MES stimulation was applied at different intervals following LTP-inducing trains over a 10 day period. High-frequency LTP-inducing stimulation resulted in amplitude changes in both early (9.28 ms to peak) and late (20.81 ms to peak) components of the evoked EPSP, as well as of the population spikes. There was a window of time following high-frequency stimulation within which MES could interrupt the induction of LTP. MES stimulation applied immediately, or 1 h after, LTP-inducing trains prevented the induction of LTP. LTP was not blocked, however, when the MES stimulation was applied 6 h after the LTP-inducing trains. MES stimulation applied to a fully potentiated animal transiently attenuated both the population spike and polysynaptic measures, but both components recovered within 24 h. These data support the idea of a consolidation gradient for neocortical LTP similar to that seen in behavioural studies.


    Introduction
 Top
 Footnotes
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Long-term potentiation (LTP) is a persistent, activity-dependent enhancement of synaptic transmission (Bliss and Lomo, 1973Go; for review see Bliss and Collingridge, 1993). It has several features that have made it an attractive memory model, including associativity (Levy and Steward, 1979Go; Brown et al., 1988Go) and longevity (Barnes, 1979Go; Racine and Milgram, 1983Go; Abraham and Otani, 1991Go). Initially discovered in the perforant path projections to the dentate gyrus, LTP has been shown to occur in many subcortical and cortical afferent pathways (Wilson and Racine, 1983Go; Racine et al., 1983Go; Kuba and Kumamoto, 1990Go; Tsumoto, 1992Go). Neocortical LTP in slice and anaesthetized animals has been difficult to produce, however, often requiring the use of GABAergic blockers and/or immature animals (Artola et al., 1990Go; Aroniadou and Teyler, 1991Go; Bear et al., 1992Go; for review see Bear and Kirkwood, 1993). Neocortical resistance to LTP induction has been even more apparent in the chronic preparation (Racine et al., 1994Go). It has only recently been shown that an NMDA-dependent LTP can be reliably induced in the neocortex of awake, freely moving animals following multiple, spaced sessions of high-frequency stimulation (Racine et al., 1995Go; Trepel and Racine, 1998Go).

Although the neocortex requires many days of stimulation in order to reach asymptotic levels of LTP, it is otherwise quite reactive. We have found that LTP can be induced with very few stimulation trains or very low stimulation intensities, so long as the stimulation is spaced and repeated (Trepel and Racine, 1998Go). This slow development of LTP contrasts with that found in the hippocampus, where asymptotic levels of LTP can often be achieved in one session of stimulation.

These differences in neocortical and hippocampal LTP induction are consistent with the differing roles that these structures are believed to play in memory. The hippocampal system has been described as a fast learning system with transient storage capabilities, while the neocortical system is believed to store information for long periods but operate with a relatively slow learning rate (Zola-Morgan and Squire, 1993Go; McClelland et al., 1995Go). Neural network modelling results have indicated that slow learning rates, together with spaced and interleaved presentations of input patterns, allow networks to store maximal amounts of information with the least amount of interference (McClelland et al., 1995Go).

In this paper we describe the effects of maximal electroconvulsive shock (MES) on neocortical LTP induction. MES has been shown to disrupt memory formation when delivered post-trial in learning tasks (Zubin and Barrera, 1941Go; Brody, 1944Go; Quartermain et al., 1965Go; McGaugh and Alpern, 1966Go; Barnes et al., 1994Go; Bohbot et al., 1996Go). MES is also used as an animal model of electroconvulsive therapy (ECT), which is used to treat depression in human populations. One of the most striking and frequently cited effects of human ECT is the memory dysfunction accompanying treatment (Squire, 1977Go; Weeks et al., 1980Go; Krueger et al., 1992Go), although the locus of this effect is unknown.

The memory-disrupting effects of MES were used extensively in attempts to define consolidation gradients, but these experiments were largely abandoned when the `gradients' were found to be dependent upon many additional variables (Polster et al., 1991Go; see Abrams, 1992 for review). In rats, MES stimulation reversibly disrupts hippocampal LTP (Hesse and Teyler, 1976Go), and LTP induction is impaired in slices taken from rats that have undergone repeated MES stimulation (Anwyl et al., 1987Go). On the other hand, MES itself has been shown to produce potentiation effects in the hippocampus (Stewart et al., 1994Go) lasting several months (Burnham et al., 1995Go) and these data have raised the possibility that the prevention of potentiation associated with the prior application of MES is itself the result of an LTP-like synaptic saturation (Stewart and Reid, 1993Go; Barnes et al., 1994Go).

The experiments presented here demonstrate that MES stimulation (i) induces a temporally graded blockade of neocortical LTP induction when administered following the application of high-frequency stimulation; (ii) transiently disrupts established LTP in the neocortex; and (iii) does not result in the LTP-like potentiation effects normally recorded in the hippocampus following the repeated application of MES.

Portions of these data have been presented previously in abstract form (Trepel and Racine, 1997Go).


    Materials and Methods
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 Footnotes
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Animals and Surgery

Thirty male Long–Evans hooded rats from the McMaster University Breeding Colonies were used in these experiments. At the time of surgery, the animals weighed 300–400 g. They were housed individually, maintained on an ad libitum feeding schedule, and kept on a 12 h on/ 12 h off light cycle.

Twisted wire bipolar electrodes were prepared from Teflon-coated, stainless steel wire (120 µm in diameter). The average tip separation was 1.0 and 0.5 mm for the recording and stimulating electrodes respectively. The animals were anaesthetized with sodium pentobarbital (65 mg/kg) and received atropine sulfate (1.2 mg/kg) to prevent respiratory distress. In each animal, a bipolar recording electrode was implanted into primary motor cortex (M1) near the border of somatosensory cortex (S1) 2.0 mm anterior and 4.0 mm lateral to the midline (Paxinos and Watson, 1997). A stimulating electrode was implanted into the forceps minor corpus callosum 2.0 mm anterior and 2.0 mm lateral to the midline. These two electrodes were adjusted during surgery to provide optimal response amplitudes. The resulting mean depths for the callosal stimulating and cortical recording electrodes were 3.0 and 1.8 mm ventral to dura respectively. The electrodes were connected to gold-plated male pins that were then inserted into a nine-pin miniature connector plug that was mounted onto the skull with dental cement and anchored with stainless steel screws. One of the screws served as the ground electrode. Data acquisition began 2 weeks following surgery.

Baseline Measures and Induction of Neocortical LTP

Three field potential measures, spaced at 48 h, were taken to establish a series of baseline input/output (I/O) curves. Pulses of increasing intensity were delivered to the corpus callosum at a frequency of 0.1 Hz. Ten responses of 50 ms were evoked, amplified, digitized (at 10 kHz) and averaged at each of ten logarithmically spaced intensities (16, 32, 64, 100, 160, 250, 500, 795, 1000, 1260 µA).

LTP-inducing stimulation sessions were delivered once every 48 h according to the schedule described below. Each session consisted of 60 eight-pulse, 24 ms trains (delivered at a frequency of 0.1 Hz). The intra-train pulse frequency was 300 Hz and the pulse duration 0.1 ms. Intensity was set at 1260 µA to maximize the LTP effects. I/O measures were taken every day during this period to monitor LTP induction. EEG activity was recorded during train delivery to ensure that epileptiform discharges were not triggered.

Maximal Electroconvulsive Shock Administration

Beginning 24 h after the third baseline I/O test, animals received MES stimulation at 2 day intervals according to group designation. The MES stimulus consisted of 150 mA, 60 Hz sine-waves delivered for 200 ms via corneal electrodes. The first group was an MES control (MES only, n = 4) which was included to verify that MES by itself had no effect on the baseline response. Animals in this group received five MES sessions spaced 48 h apart over a total of 10 days. The second, third and fourth groups received 60 high-frequency trains once every 48 h, followed 5 min (MES 5 min after trains, n = 6), 1 h (MES 1 h after trains, n = 5) or 6 h (MES 6 h after trains, n = 5) later by MES stimulation. A fifth group (trains only, n = 5) received high-frequency trains alone every 48 h to provide a baseline level of LTP. I/O measures were collected every day. On the days when high-frequency trains and MES stimulation were delivered, the I/O measures were collected immediately preceding the administration of high-frequency trains. These regimens were followed for 10 days. One week following the trains/MES protocol, animals that received MES alone, MES immediately or MES 1 h after trains were given 60 high-frequency trains every 48 h in the absence of MES stimulation for 10 days to confirm that LTP could be induced in these animals. I/O measures were again collected daily throughout the LTP induction procedure, and were subsequently collected for 2 weeks following the delivery of trains.

A separate group of animals (n = 5) received 60 high-frequency trains every 48 h for 10 days and then received a single MES stimulation to determine the effects of MES on an already established LTP. This was done to test for depotentiation effects of MES. I/O measures were collected each day throughout the LTP induction procedure and were then collected 5 min, 30 min, 1 h, 6 h, 12 h and 24 h following the MES stimulation.

Analyses

Changes in the field potentials over LTP-induction and decay sessions were measured by subtracting the final baseline responses from all other baseline and potentiated responses at a single I/O intensity that best reflected potentiation of the late component. The intensity that evoked a response that was approximately half the maximum amplitude was chosen for analysis. This was the fifth intensity in the I/O series (160 µA) in almost all cases.

The early (average latency-to-peak 9.28 ms) and late (average latency-to-peak 20.81 ms) components were measured at fixed latencies corresponding to the peak response of the components being analysed (Fig. 3Go shows where both early and late component measures were taken in a typical response). The early component reflects both population EPSPs and population spikes (Chapman et al., 1998Go). The population spikes are distributed over the full duration of the early component, their polarity (in our bipolar recordings) is opposite to that of the population EPSP, and they show a large potentiation effect. Consequently, there is often a polarity reversal in the early component measure following LTP induction. We measured the full amplitude shift (in mV) from the baseline to the potentiated response.



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Figure 3.  Representative sweeps recorded before (solid) and after (dashed) the LTP induction regimen for groups that received high-frequency trains alone (A), high-frequency trains followed 6 h (B), 1 h (C) or 5 min (D) later by MES stimulation or MES stimulation alone (E). Also shown in (A) are examples of the cursor positions used to measure the changes in the early (left cursor) and late (right cursor) response components. All response components were enhanced following the delivery of high-frequency stimulation alone, or high-frequency trains followed 6 h later by MES stimulation, but LTP was blocked when MES was delivered 1 h or 5 min after the high-frequency trains. Note that, unlike previous reports for the hippocampus, MES stimulation alone did not induce potentiation. All sweeps were evoked at 160 µA. Vertical calibration: 1.0 mV; horizontal calibration: 10 ms.

 
The late components are polysynaptic (Chapman et al., 1998Go), and they also show a strong potentiation effect. In some animals, the late component peaks are not always clear prior to the induction of potentiation. Consequently, control animals were analysed using the means of the latencies determined from the experimental animals. Again, we measured the amplitude shift, following the LTP induction in the experimental animals, from the baseline to potentiated levels.

High-frequency stimulation produces an amplitude shift in the early component that reflects primarily population spike potentiation. An additional population spike measure was taken from the largest amplitude response in the I/O tests, immediately before and 24 h after LTP induction. The height (in mV) of all population spikes within a response were measured from their respective turnover points and then summed to provide a measure of total spike height for that response. The very first downward-going spike in each sweep also potentiates, but it was excluded from the calculations because of possible contributions of antidromic effects or distortions due to the stimulus artifact (see Chapman et al., 1998).

Repeated-measures ANOVAs were calculated over the induction and post-MES periods. Following collection of all electrophysiological measures, animals were perfused and the brains were sliced and stained with Cresyl Violet to verify electrode placements.


    Results
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 Footnotes
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Histology

The stimulating electrode spanned the forceps minor corpus callosum in all animals. The ventral tips of the recording electrodes were placed in anterior primary somatosensory cortex (S1) or the posterior aspect of primary motor cortex (M1) (Paxinos and Watson, 1997) in all cases.

Response Morphologies

Neocortical field potentials were similar to those described previously (Chapman et al., 1998Go; Trepel and Racine, 1998Go). Briefly, they appeared to have two main components: an early surface-negative response (average latency-to-peak 9.28 ms, range 7.0–11.0 ms), and a larger (post-LTP) late response (average latency-to-peak 20.81, range 17.0–25.5 ms). Superimposed on the early response in all cases were at least one, and usually several, population spikes which typically grew in amplitude and number following potentiation. Representative preand post-LTP sweeps from each of the experimental groups are shown in Figure 3Go.

Behaviour

Most animals (~90%) showed an ipsilateral postural deflection during delivery of the trains. These animals did not appear to potentiate any differently from animals that did not show this reaction. Additionally, many animals displayed strong cortical spindles following high-frequency trains or test pulses of 250 µA and above. The presence or absence of cortical spindles showed no relationship with the incidence or magnitude of the neocortical LTP effects. None of the animals showed any evidence of seizure activity during, or post-ictal depression following, the stimulation protocols.

Animals that received MES stimulation reliably displayed a tonic–clonic convulsion which lasted between 10 and 25 s. The severity of the seizures appeared to increase slightly as the experiment progressed.

Experiment 1: Temporally Graded Blockade of Neocortical LTP with MES Stimulation

The repeated application of electroconvulsive shock blocked the induction of neocortical LTP in a temporally graded fashion. Figure 1Go shows changes in the early and late components for control animals and animals receiving MES immediately, 1 h or 6 h following high-frequency stimulation. There was a significant interaction effect between session and group for the early component [F(48,240) = 2.85, P < 0.001]. The animals receiving trains alone potentiated normally, showing an amplitude shift in the early component that was dominated by an increase in population spike amplitude (Chapman et al., 1998Go). The result of this potentiation is that the early component is first reduced, and then, with further potentiation, reverses polarity. There was a nearly complete blockade of this amplitude shift in the animals receiving MES immediately after the trains. A substantial suppression of LTP was also seen in the groups receiving MES at 1 h and 6 h after the trains. MES alone had no effect. The related population spike measures showed a significant interaction effect between session and group [F(4,20) = 2.87, P < 0.04]. The control group and the groups that received MES 1 h and 6 h after trains all showed population spike enhancements, while the animals that received MES either immediately after trains or alone showed reductions in population spike amplitude (Fig. 2Go). These changes can be clearly seen in Figure 3Go, where representative sweeps are shown for single animals from each of the experimental groups. These sweeps demonstrate that a substantial LTP was induced in all response components in the animals that received high-frequency trains either without MES or with a delayed (6 h) MES. The other groups do not appear to have potentiated.



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Figure 1.  The effects of MES applied at different intervals on the induction of long-term potentiation. The mV differences between the last baseline and all other sweeps are plotted in these figures for the baseline (pre-LTP) and LTP induction (LTP) periods. Top: Changes in the early component over days. Animals that received high-frequency train sets every 48 h showed a strong amplitude shift in the early component (indicated as a negative mV shift from baseline). We have plotted these curves in the downward direction, because the population spike potentiation produces an amplitude shift in a direction opposite to the population EPSP in our bipolar recordings (see Figs 3 and 6GoGo). Animals that received similar high-frequency train sets followed immediately, 1 h later or 6 h later by MES stimulation showed a reduced early component effect. Animals that received MES alone showed a negligible change in the early component. Bottom: Changes in the late component over days. Only those animals receiving LTP-inducing trains alone or trains followed 6 h later by MES showed a significant enhancement of the late component. All other groups showed no change from baseline. Note that, contrary to the effects seen in the hippocampus, MES administered alone does not cause potentiation of the late components. All measures were taken from sweeps that represented the half-maximal response amplitude (160 µA for most animals).

 


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Figure 2.  Total population spike height measures are shown for time-points prior to LTP induction (pre-LTP) and 24 h following the induction protocols (post-LTP). Animals that received LTP-inducing trains alone and those that underwent MES 6 h following trains showed population spike enhancements, while animals in all other groups showed no enhancement. Note that animals in the MES only and 1 h MES conditions appeared to show small decreases in population spike height.

 
There was also a significant interaction between group and session for the late component [F(48,240) = 6.06, P < 0.001]. For this component, only the animals that received 48 h spaced trains alone, and those animals that received MES 6 h following trains showed potentiation of the late components, with the latter showing approximately half as much potentiation as the former.

The groups in which potentiation was blocked by MES were left for 1 week and then repotentiated. All of these animals showed potentiation of all components. This indicates that the application of MES stimulation did not cause long-lasting deleterious effects.

Experiment 2: MES Disruption of Previously Established LTP

To test for possible depotentiating effects of MES, we applied MES to animals in which LTP had already been established. The effects of MES stimulation on the early and late components of fully potentiated neocortical responses are shown in Figure 4Go. There was an overall effect of session for both the early [F(18,72) = 2.30, P < 0.01] and late [F(18,72) = 16.63, P < 0.001] components. The application of MES caused some increase in variability, but the most striking effect was a shift in amplitude back towards baseline levels. This effect, however, lasted for <12 h. The population spike amplitudes, which showed a significant effect of session [F(7,28) = 6.21, P < 0.001], were also depressed by MES (Fig. 5Go). These amplitudes were reduced to baseline levels when measured 5 min following MES, and then recovered over the next 24 h. By 24 h, the group measures were no longer significantly different from their potentiated levels (Tukey's HSD test: P > 0.36). Figure 6Go shows a set of representative sweeps taken before and after LTP induction, and following the six post-MES time-points (5 min, 30 min, 1 h, 6 h, 12 h and 24 h).



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Figure 4.  The effects of a single MES seizure on a fully potentiated neocortical evoked potential. The mV differences between the last baseline and all other sweeps are plotted in these figures for the baseline (pre-LTP), LTP induction (LTP) and post-MES (post-MES) periods. Top: Changes in the early component over days. The application of MES appeared to cause a small loss of the amplitude shift normally associated with potentiation of this component, though it was still well within the range of a potentiated response. Bottom: Changes in the late component over days. Along with the population spikes, this component showed the largest effect overall, being reduced to a near-baseline state for a period of ~1 h. Thereafter, the late component recovered back to its fully potentiated level within 12 h.

 


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Figure 5.  Total population spike height measures are shown for time-points prior to LTP induction (pre-LTP), following the induction of LTP (LTP) and at various times following a single session of MES (5 min, 30 min, 1 h, 6 h, 12 h and 24 h following MES). Five minutes following the application of MES the population spikes were significantly depressed. By 30 min post-MES they had recovered to a point where they were no longer statistically different from pre-MES responses.

 


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Figure 6.  Representative sweeps recorded during the course of recovery from the effects of a single session of MES. The first set of sweeps (A) shows a baseline (solid) response compared to a fully potentiated response (dashed). The next six sets of sweeps compare a fully potentiated response (solid in all cases) to a response recorded 5 min post-MES (B), 30 min post-MES (C), 1 h post-MES (D), 6 h post-MES (E), 12 h post-MES (F) and 24 h post-MES (G). The response in this animal had returned to near baseline levels by 6 h post-MES (E). All sweeps were evoked at 160 µA. Vertical calibration: 1.0 mV; horizontal calibration: 10 ms.

 

    Discussion
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 Footnotes
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The present study was designed to investigate the effects of MES stimulation on the induction and expression of neocortical LTP in the awake, freely moving rat. The induction of neocortical LTP was interrupted or blocked by the application of MES stimulation 5 min or 1 h after the administration of high-frequency trains. These data are in agreement with previous hippocampal studies in which the repeated application of MES stimulation served to suppress the induction of hippocampal LTP by as much as 83.5% (Hesse and Teyler, 1976Go; Anwyl et al., 1987Go). On the other hand, a recent study has shown that hippocampal LTP could be enhanced by pairing high-frequency stimulation with MES (Barnes et al., 1994Go). This difference might be due to the lack of a delay between the high-frequency stimulation and the MES in the latter study. Our shortest delay was 5 min and resulted in a complete block of LTP induction in our neocortical site. We were surprised to find that MES alone produced no potentiation effects in the neocortical response. Such effects have been found in the hippocampus (Stewart et al., 1994Go; Burnham et al., 1995Go).

Neocortical GABAergic systems may be more strongly engaged, and potentiated, in response to the convulsive stimuli. An enhanced inhibition might then act against the development of potentiation at excitatory synapses and thereby prevent the induction of neocortical LTP. Another possibility is that the activation of alternate pathways, during MES, might lead to a heterosynaptic long-term depotentiation effect. Similarly, the potentiated pathways might be activated at a low frequency during MES, or the subsequent seizure discharge, leading to a homosynaptic depotentiation effect. In either case, the potentiating trains and the MES stimulation must occur within about a 1 h window, because we found only weak effects in the 6 h group and MES produced no long-lasting depotentation of previously established LTP. Hesse and Teyler (1976) also showed a partial or complete reversal of existent LTP with MES stimulation. Our responses, however, returned to their fully potentiated levels within 12 h post-MES, confirming that the blockade of LTP induction by MES was not due to some non-specific decrease in excitability of the tissue. Further research into the interactions between LTD and depotentiation is required before the role of depotentiation phenomena can be accurately assessed.

There have been a number of short-and long-term changes reported following repeated MES seizures. These include the down-regulation of ß-adrenergic receptors (Pandey et al., 1979Go) and increases in both serotonin-2 (Biegon and Isreali, 1987Go) and {alpha}2-adrenergic receptors (Stockmeier et al., 1987Go). One of the most interesting changes, however, is the increase observed in neuropeptide-Y (NPY) levels following MES stimulation. NPY immunoreactivity (Wahlestedt et al., 1990Go; Stenfors et al., 1992Go; Kragh et al., 1994Go) has been shown to increase in both the hippocampus and neocortex in response to MES. There is also considerable evidence that NPY may modulate memory. Intraventricular administration of NPY enhances memory retention for T-maze footshock avoidance and step-down passive avoidance training in mice (Flood et al., 1987Go, 1989Go). NPY administration post-training, however, produces a dose-dependent, inverted U-shaped dose–response curve for task retention (Flood et al., 1987Go; for review of effects of NPY on memory, see Morley and Flood, 1990).

It is possible that MES stimulation, following high-frequency stimulation, is causing a sudden increase in NPY levels, resulting in compromised potentiation. Bath application of NPY causes a long-lasting, reversible reduction of the orthodromic EPSP recorded intracellularly from CA1 pyramidal neurons in in vitro preparations (Colmers et al., 1987Go). This work has led to the assertion that NPY acts presynaptically in the CA1 region to reduce excitatory input to pyramidal neurons (Colmers et al., 1987Go), a hypothesis supported by the subsequent observation that NPY directly suppresses synaptic transmission in CA1 (Klapstein and Colmers, 1993). This reduction in excitation may serve to suppress events that normally follow high-frequency stimulation, thereby weakening or preventing the induction of LTP.

Electroconvulsive stimulation can produce a retention deficit if it is administered shortly following a learning task in both rats (e.g. Quartermain et al., 1965) and humans (Squire et al., 1981Go; for review see Abrams, 1992). The severity of this deficit declines with the interval between the learning task and ECS administration (McGaugh and Herz, 1972Go; Maki, 1985Go; Bohbot et al., 1996Go). This retrograde amnesia gradient is believed to reflect the time course of memory consolidation, but, as we indicated in the Introduction, it is influenced by many variables. Bohbot et al. (1996) trained rats in the Morris water maze and then applied ECS at varying intervals following a single escape to the new platform location. In this study of spatial learning, memory was disrupted when ECS was applied 0–15 s after a learning trial. At intervals of 30 s and longer, however, the ECS had no effect. On the other hand, Gold et al. (1973) paired inhibitory avoidance training in rats with ECS delivered directly to the neocortex and demonstrated retrograde amnesia gradients between 5 s and 240 min. The length of the gradient depended on the location and intensity of the stimulation. The longest of these gradients fall between our 1 h and 6 h time-points, indicating some compatibility with our data. The similarity between some of the demonstrated consolidation gradients for learning tasks, and the gradients demonstrated here for LTP, raises the possibility that similar mechanisms may be engaged in each process. As pointed out earlier, however, consolidation gradient analyses are difficult to interpret, because of the highly variable outcomes. Nevertheless, the LTP suppression demonstrated here may represent one way by which memory consolidation can be disrupted by electroconvulsive shock.


    Notes
 
This work was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) to R.J.R., and an NSERC Postgraduate Scholarship to C.T.

Address correspondence to Dr R. J. Racine, Department of Psychology, McMaster University, Hamilton, Ontario, Canada L8S 4K1. Email: racine{at}mcmaster.ca.


    Footnotes
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 Footnotes
 Abstract
 Introduction
 Materials and Methods
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 Discussion
 References
 
1 Present address: W.M. Keck Foundation Center for Integrative Neuroscience and Department of Physiology, Box 0444, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA Back


    References
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 Footnotes
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
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