Contextual Conditioned Fear Blocks the Induction But Not the Maintenance of Lateral Septal LTP in Behaving Mice
René Garcia,
Rose Marie Vouimba, and
Robert Jaffard
Laboratoire de Neurosciences Comportementales et Cognitives, Centre National de la Recherche Scientifique, Unité de Recherche Associée 339, Université de Bordeaux I, 33405 Talence, France
 |
ABSTRACT |
Garcia, René, Rose Marie Vouimba, and Robert Jaffard. Contextual conditioned fear blocks the induction but not the maintenance of lateral septal LTP in behaving mice. J. Neurophysiol. 78: 76-81, 1997. High-frequency stimulation (HFS) of the fimbria induces long-term potentiation (LTP) in the lateral septum. This study was aimed at investigating the effect of contextual fear conditioning on septal LTP with the use of behaving C57 BL/6 mice as subjects. For the acquisition of contextual fear conditioning, animals were placed in a conditioning chamber, where they were subjected to footshocks (FSs, 0.6 mA); the following day (retention), animals were reexposed to the chamber. Animals from the first group received HFS in their home cages before being submitted to conditioning; animals from the second group were first submitted to conditioning before receiving HFS during reexposure to the conditioning chamber; animals from the third group were submitted to the same regimen as those from the second group, except that no FS was delivered in the conditioning chamber; and animals from the fourth group received FS in the conditioning chamber but were maintained in their home cages the day after for LTP induction. Before conditioning, animals from the first group, placed in a familiar context (home cage), displayed an LTP of the N3 wave of septal field potential. After conditioning, reexposure of these animals to the conditioning chamber produced a transient decrease in the amplitude of N3 but did not interfere with the duration of maintenance of LTP. Conversely, in animals from the second group, when HFS was applied during reexposure to the conditioning chamber the induction of LTP was totally blocked. However, mice from the two other groups (3rd and 4th) displayed normal levels of LTP. Taken together with previous findings, these data suggest that contextual conditioned fear may interfere with certain forms of learning via blockade of hippocampal-septal LTP.
 |
INTRODUCTION |
Anatomic studies have shown that a major afferent projection to the lateral septum (LS) arises from the hippocampal formation by the way of the fimbria fibers (Raisman 1966
; Staiger and Nürnberger 1989
; Swanson and Cowan 1979
). More recently, a number of biochemical and electrophysiological studies have provided evidence that the hippocampal input to the LS is mediated by the excitatory amino acid glutamate (Joëls and Urban 1984; Storm-Mathisen and Woxen-Opsahl 1978
; Zaczek et al. 1979
). Using rat LS slices, Van den Hooff et al. (1989)
showed that high-frequency stimulation (HFS) of these glutamatergic fimbria fibers induced a long-lasting increase in the amplitude of the evoked LS field potential. Our recent studies, carried out with the use of anesthetized mice, showed that a subset of hippocamposeptal synapses (corresponding to the negative N3-evoked component of the LS field potential) exhibited a similar long-lasting increase in efficacy following HFS of fimbria fibers (Garcia and Jaffard 1992
, 1993
). This experimentally induced increase in synaptic efficacy in the LS corresponds to the phenomenon known as long-term potentiation (LTP). LTP of intrinsic pathways of the hippocampal formation has attracted much attention because it may represent an artificial induction of the type of plasticity that has been postulated to occur naturally during memory formation in tasks for which the hippocampus is necessary (Lynch and Baudry 1984
; Teyler and DiScenna 1984
). Several types of experiments have attempted to provide experimental support for this hypothesis, among them manipulations that both block the induction of hippocampal LTP and also interfere with learning (Grant et al. 1992
; Morris et al. 1986
; Staubli et al. 1989
; Silva et al. 1992
; for review see Martinez and Derrick 1996
). Most specifically, some experiments have been conducted with the aim of relating the detrimental effect of exposure to aversive and stressful events on acquisition of learning tasks to the impairment of LTP in intrinsic pathways of the hippocampal formation. On the whole, these experiments have provided evidence that, in certain conditions, stress can interfere with the induction of hippocampal LTP (Diamond et al. 1990
; Shors et al. 1989
), but without necessarily interfering with the acquisition of hippocampal-dependent learning (Warren et al. 1991
).
Recent experiments have shown that the acquisition of certain learning tasks in both mice (Garcia et al. 1993
, 1995
; Jaffard et al. 1996
) and rats (Urban et al. 1995
) was associated with long-lasting changes in synaptic efficacy in the LS, and that the magnitude of these changes was related to the ability of individuals to master the task. One can thus suppose that conditioned fear, which has previously been shown to acutely modulate hippocampal-septal synaptic transmission (Garcia and Jaffard 1996
), may, at least in part, interfere with learning through alterations in these training-induced long-lasting changes in synaptic weight in the LS.
In this study we present experiments that address this question. Using behaving mice as subjects, we show that Pavlovian fear conditioning to contextual conditioned stimuli (CSs), but not previous exposure to the physical stressor (unconditioned stimulus, US), interferes with the induction but not the maintenance of LTP in the LS.
 |
METHODS |
Subjects and surgery
The experiments were performed with the use of young (4-6 mo) male mice of the C57 BL/6 JI Co strain weighing between 28 and 32 g at the time of surgery. They were individually housed in a room (23°C) with a 12-h light:dark cycle. For the implantation of electrodes, animals were anesthetized with pentobarbital sodium (100 mg/kg ip). The stimulating and recording electrodes were made of two twisted platinium-iridium wires (90 µm diam) insulated except at the tip. These were respectively positioned in the fimbria (0.6 mm posterior to bregma and 0.6 mm lateral to midline) and the LS (1 mm anterior to bregma and 0.4 mm lateral to midline) at a location generating a maximum amplitude of the field potential negative complex (comprising the N2 and N3 waves). The entire miniature system was fixed in place with dental cement. Mice were then allowed to recover in their home cages for 10 days before recording sessions. The animals had continuous access to food and water. Animals were handled daily from the 3rd day postsurgery to the end of experiment.
Stimulating and recording procedures
LS field potentials evoked by single-pulse fimbria stimulation (0.1-ms rectangular biphasic pulses) were recorded through JFET operational amplifiers placed on the heads of the animals and amplified (gain = 1,000, band-pass filtered at 1-1,000 Hz), displayed on an oscilloscope, recorded by a microcomputer for on-line averaging (each average was established with 17-20 responses at 0.2 Hz), and stored on disks for off-line analysis. Stimulation intensity was chosen (from the baseline input/output curves: 60-600 µA) according to what produced a response representing ~80% of the maximal level.
To determine whether the excitatory negative components of the field potential (i.e., N2 and N3) are synaptic responses or are generated by LS cell firing, extracellular single-unit activity were recorded on mice (n = 10) acutely prepared under anesthesia. Fimbrial stimulation was performed as above, but with low stimulation intensities. LS responses were recorded with the use of glass microelectrodes filled with 2 M-NaCl, having tip diameters of 1-10 µm and DC resistances in saline between 1 and 5 M
. The responses were filtered, amplified (band pass: 0.3-10 kHz,gain = 10,000 for unitary activity; band-pass: 1-1,000 Hz,gain = 1,000 for field potentials) and displayed on an oscilloscope for printing. Recording placements were determined by the response pattern of the recorded field potential (Fig. 1).

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| FIG. 1.
Example of unit activation during fimbrial-stimulation-evoked septal field potential. Traces were recorded with same electrode with different filter settings adjusted to reveal either field potential or single-unit activity. Latency of single-unit activity coincided with peak latency of N3 component of field potential.
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Experimental protocol
The baseline was established over a 4-day period (1 recording session per day). For each recording session, animals were maintained in their home cages, which were transferred from the animal room to the room used for electrophysiological tests. Immediately after the last recording session on day 4, animals were randomly divided into 4 groups. Animals from the first group (HFS/FS-cc group, n = 7) received HFS of the fimbria in the home cage before being submitted to contextual fear conditioning with the use of footshocks (FSs). Twenty-four hours later, these animals were reexposed to the conditioning chamber (cc) for electrophysiological recording as described below. Animals from the second group (FS/HFS-cc group, n = 6) were first submitted to contextual fear conditioning and received HFS of the fimbria the following day, i.e., during reexposure to the conditioning chamber. The two other groups were submitted to the same regimen as the second one except that for the third group (NFS/HFS-cc group, n = 6), no FS was delivered in the conditioning chamber, whereas animals of the 4th group (FS/HFS-hc group, n = 6) that had received FSs in the conditioning chamber were not reexposed to the chamber the day after but were maintained in their home cages for LTP induction. For all groups, HFS of the fimbria consisted of three trains (0.2 Hz) of 200 pulses at 200 Hz that produced significantly larger LTP than a train of 100 pulses over a 1-s period (100 Hz, see Fig. 3A, left).

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| FIG. 3.
A: mean N3 wave amplitude in the HFS/FS-cc group (left) during baseline establishment (days 1-4), following (day 4 at +15 min, +1 h, and +24 h) fimbrial HFS at either 100 or 200 Hz, and (right) at different time periods (day 6) during reexposure to conditioning chamber (200-Hz group alone) 24 h after conditioning on day 5. Triple asterisk: significantly different from baseline (post hoc Scheffé F tests): P < 0.001. B: mean N3 wave amplitude during baseline establishment (left), and (right, day 6) before ( 10 and 6 min) and after (+15 min, +1 h, and +24 h) tetanus given either in conditioning chamber (the 2 cc groups) or in home cage (hc group) following (the 2 FS groups) or not (NFS group) conditioning on day 5. Double asterisk: significantly different from the 2 other groups (post hoc Scheffé F tests): P < 0.01. Section symbol: significantly different from the FS/HFS-cc group (post hoc Scheffé F tests): P < 0.05. Time periods of the 1st 2 recording sessions on day 6 (20 s and 4 min in A, and 10 and 6 min in B) were very closed with respect to beginning of reexposure to conditioning chamber, so that a direct comparison of N3 wave amplitude between the HFS/FS-cc (A) and FS/HFS-cc (B) groups can be performed (see RESULTS).
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FSs were administered in a gray plastic chamber (30 × 24 × 22 cm) equipped with a stainless steel grid floor connected to a shock generator. Two minutes after being placed in this conditioning chamber, mice were subjected to 4 FSs (0.6 mA, 2 s in duration, 20 s apart), each of which was capable of inducing the startle reflex and sometimes the emission of a vocalization. Immediately afterward, mice were replaced in their home cages and transferred to the animal room. Twenty-four hours later, animals were placed back into the conditioning chamber (except for the 4th group, see above) for a period of ~1 h, during which the animals were left undisturbed. For the HFS/FS-cc group, field potentials were recorded at the beginning (20 s and 4 min) and at the end (1 h) of the session. For the three other groups (i.e., FS/HFS-cc, NFS/HFS-cc, and FS/HFS-hc), two recording sessions were performed during the first 10 min that preceded the delivery of HFS and, as for the HFS/FS-cc group (see Fig. 3A, left), at 15 min, 1 h, and 24 h after that stimulation (see Fig. 3B, right).
Histology and data analysis
After completion of experiments, all mice were given an overdose of pentobarbital sodium and perfused with saline (0.9%) followed by Formalin (10%). The exact placement of the electrodes was then verified by conventional histological methods.
Changes in the N3 wave amplitude are presented as the means ± SE of the individual values of animals from each group. Statistical analysis of the data was performed with the use of analysis of variance (ANOVA).
 |
RESULTS |
Lateral septal responses to fimbria stimulation
Fimbria stimulation evoked characteristic field responses in the LS (Garcia and Jaffard 1992
, 1993
, 1996
; Garcia et al. 1993
, 1996
). Single stimuli delivered to fimbria evoked single action potentials in LS neurons, the latency of which (varying from 6 to 10 ms, mean = 7.5 ms, n = 14) coincided with the excitatory negative N3 component of the field potentials (Fig. 1). Moreover, the majority of such neurons was located in the same area from which the amplitudes of the N3 component were highest and the latencies shortest.
Effects of tetanus frequency
The amplitudes of negative components (N2 and N3) of the field potential were measured according to the method described previously (Garcia and Jaffard 1992
, 1993
, 1996
). Only the N3 component displayed an increase in amplitude following the stimulation train (see Fig. 2). As shown in Fig. 3A, left, HFS paradigm at 200 Hz resulted in a larger increase in the amplitude of N3 (LTP) than at 100 Hz. A two-way ANOVA with recording periods (7 levels) as within-subjects factor and frequency (200 vs. 100 Hz) as between-groups factor indicated a significant period × group interaction [F(6,66) = 11.3, P < 0.001]. In the 200-Hz group, one-way ANOVA indicated that the amplitudeof N3 changed significantly during the recording sessions[F(6,36) = 36.2, P < 0.001]. Post hoc Fischer tests revealed that significant LTP first occurred following (15 min, 1 h, and 24 h) the 200-Hz stimulation (all P values <0.001). The same analysis performed on data from the 100-Hz train revealed that although there were significant changes in the N3 amplitude during recording sessions [F(5,30) = 3,26, P < 0.05], the changes that followed the 100-Hz traindid not reach statistical significance (Fisher tests, all P values >0.05).

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| FIG. 2.
Top: representative example of changes in field potentials recorded in a subject of the HFS/FS-cc group. Top left: during baseline establishment in home cage (hc). Top middle: 1 h after high-frequency stimulation (HFS). Top right: 24 h after footshocks (FSs) in conditioning chamber (cc). Bottom: representative example of field potentials recorded in a subject of the FS/HFS-cc group. Bottom left: during baseline establishment. Bottom middle: 24 h after FS in conditioning chamber. Bottom right: 1 h after HFS given in conditioning chamber.
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Effects of conditioned fear stress on the maintenance of LTP
Twenty-four hours after the induction of LTP, animals were transferred from their home cages (where pre- and post-LTP recordings were performed) to the conditioning chamber for contextual fear conditioning. As shown in Fig. 3A, right, the day after conditioning, when animals were reexposed to the conditioning chamber, the amplitude of N3 remained slightly but not significantly above baseline. Importantly, however, the amplitude of N3 was significantly greater (HFS/FS-cc group: 20 s, 104.6 ± 5.6%, mean ± SE; 4 min, 105.1 ± 7.2%) than that recorded at the same time periods in the FS/HFS-cc group (see Fig. 3B, right), which was submitted to the same regimen but had not yet been subjected to HFS [74.0 ± 9.3% and 81.3 ± 7.2%, F(1,11) = 7.6 and 6.2, P < 0.02 and P < 0.05, respectively]. A two-way ANOVA performed on data from these two groups (4 baselines + 2 periods × 2 groups) also indicated a significant period × group interaction [F(5,55) = 6.6, P < 0.001].
Effects of contextual fear conditioning on the induction of LTP
Results are summarized in Fig. 3B. A two-way ANOVA indicated that before conditioning, the amplitude of N3 was stable across the 4 days of baseline recording sessions in home cages, with no significant between-group difference norgroup × session interaction (all F values <1, see Fig. 3B, left). When reexposed to the conditioning chamber (Fig. 3B, right), animals that had received FSs the day before (the FS/HFS-cc group) displayed a reduction (20-25%) in the amplitude of N3 with respect to animals that had not received the FSs (NFS/HFS-cc group). Although of weaker magnitude, there was also a tendency for animals that received FSs but that were maintained in their home cages (the FS/HFS-hc group) to exhibit a reduction in the amplitude of N3 (~10% with respect to the NFS/HFS-cc group). A two-way ANOVA performed on these data indicated that, with respect tobaseline, there was a significant session × group interaction[F(10,75) = 3.79, P < 0.001], with, as revealed by repeated-measures ANOVA, no significant change in the amplitude of N3 in the NFS group [F(5,25) = 0.53] but significant changes in both the FS/HFS-cc group [F(5,25) = 7.0, P < 0.001] and the FS/HFS-cc group [F(5,25) = 3.41, P < 0.05]. To compensate for individual differences in the degree of conditioned-fear-induced decreases in N3 amplitude (in both the FS/HFS-cc and the FS/HFS-hc groups), the intensity of subsequent tetanic stimulation was individually adjusted (increased) to evoke an N3 wave amplitude as close as possible to baseline. The intensity of pulses used for subsequent posttetanic recordings was readjusted to the pretetanic value. As shown in Fig. 3B, right, a stimulation train at 200 Hz resulted in an increase in the amplitude of N3 (LTP) in both the NFS/HFS-cc and FS/HFS-hc groups but not in the FS/HFS-cc group. A two-way ANOVA with recording periods in the conditioning chamber (5 levels) as within-subjects factor and the three groups as between-groups factor indicated a significant period × group interaction [F(8,60) = 5.83, P < 0.001]. Specifically, in both the NFS/HFS-cc and FS/HFS-hc groups, one-way ANOVA indicated that the amplitude of N3 changed significantly during the recording sessions [F(4,20) = 19.0 and 19.6, respectively, P values <0.001]. Post hoc Fisher tests revealed that in both groups, significant LTP first occurred following (i.e., 15 min, 1 h, and 24 h) the 200-Hz train (all P values < 0.01). The same analysis performed on data from the FS/HFS-cc group did not reveal any significant changes in the amplitude of N3 [F(4,20) = 1.90, P > 0.15]. Finally, it may be noted that, with respect to baseline, the magnitude and time course of LTP in the three groups that displayed LTP (including the group that was subjected to HFS before conditioning, see Fig. 3A, left) were highly similar with respect to baseline [2-way ANOVA, session (7 levels) × group interaction: F(12,96) = 0.77].
 |
DISCUSSION |
The major finding in the present study is that conditioned fear, elicited by reexposure to the specific context (conditioning chamber) wherein animals had received FSs 24 h previously, totally blocked the induction of lateral septal LTP. However, once induced, conditioned fear does not affect its maintenance. Moreover, the presently observed blockade of LTP cannot be a simple result of previous exposure to the FSs themselves, because animals that were not reexposed to the conditioning chamber but that were maintained in their home cages (the FS/HFS-hc group) displayed normal levels of LTP.
In the present experiments, no significant changes were observed for the N2 wave component of the field potentials evoked by fimbria stimulation. Our previous recording data on depth profiles of these field potentials with the use of anesthetized mice revealed that 1) the N2 and N3 waves are mediated by depolarization of target cells that 2) represent the responses of the dorsal (N3) and ventral (N2) populations of neurons located in the medial part of the LS, and that 3) only the amplitude of the N3 component displayed a long-lasting enhancement following HFS of the fimbria (Garcia and Jaffard 1992
, 1993
). Combining these observations with the present findings and those discussed below, mediodorsal LS synapses thus appear to be more prone to exhibit both HFS-induced and behaviorally induced plastic changes than the more ventral synapses. It must be noted that in previous in vivo and in vitro studies on LTP in the LS of the rat (Racine et al. 1983
; Van den Hooff et al. 1989
), the authors did not distinguish the two N2 and N3 components. Although we used a tetanic stimulation paradigm (i.e., 3 trains at 0.2 Hz of 200 pulses at 200 Hz) different from the one used in our previous studies carried out in anesthetized mice (20 trains at 0.2 Hz of 8 pulses each at 400 Hz) (Garcia and Jaffard 1992
, 1993
), our present data again show that only the amplitude of the N3 wave displayed a significant increase. Single action potentials recording performed in the present study are consistent with the electrophysiological findings of McLennan and Miller (1974)
showing that the latency of the action potentials caused by fimbrial stimulation coincided with the N3 wave. This result and the ability of the N3 component to follow a relatively high frequency of stimulation (see Garcia and Jaffard 1992
) suggest that this component of the field potential is monosynaptic and generated by cell firing.
Recent experiments have provided evidence that the acquisition of several learning tasks in mice (Garcia et al. 1993
, 1995
; Jaffard et al. 1996
) and rats (Urban et al. 1995
) is associated with long-term changes in synaptic efficacy in the LS. Specifically, depending on the form of memory under investigation (i.e., spatial reference vs. working memory) and/or the ability of each individual to master the task (Garcia et al. 1993
; Jaffard et al. 1996
; Urban et al. 1995
), both testing-induced enhancement (LTP) and depression (long-term depression, LTD) of synaptic transmission in the LS have been reported. Of particular interest in the present context are the recent findings of Urban et al. (1995)
showing that, in rats, high shuttle box (active avoidance) performance is associated with LTP induction in the LS, whereas low shuttle box performance is associated with LTD. Indeed, it was suggested that the low performance in the shuttle box task may be, at least partially, due to a conflict between conditional freezing behavior to the CSs and running to the safe compartment. Accordingly, it is possible that an increase in activity of LS neurons via LTP may facilitate the initiation of the active conditioned response to the tone conditioned stimulus (CS) by reducing contextual conditioned fear. Such a hypothesis seems congruent with several findings. First, it has been shown that conditioned inhibitors of fear produce an increase in unit activity in the LS (Thomas 1988
; Thomas et al. 1991
). Second, recent experiments (Garcia and Jaffard 1996
) in which Pavlovian fear conditioning was used both to CSs and to a phasic auditory cue (CS) showed that when the tone CS was made predictive of the shock US (by pairing the tone CS and the US), subsequent reexposure to the context alone did not produce the decrease in septal excitability that was otherwise observed either when the CS and US were unpaired or when, as presently observed (see Fig. 3B, right, before tetanus), the tone CS was omitted. Third, vasopressin, which has been shown both to increase the transmission between fimbria fibers and LS neurons and to facilitate maintenance of LTP in the LS (Van den Hooff et al. 1989
), is known to markedly improve active avoidance learning when administered either peripherally (De Wied 1991
) or intraseptally (Engelman et al. 1992
).
Taken as a whole, these data suggest that the level of excitability of LS neurons might play a role in attention to more significant (i.e., predictive) events. More specifically, an increase in lateral septal cell excitability would favor attention to the more (predictive) tone CS while overshadowing the less predictive (background) context, whereas a decrease in septal excitability would be associated with attention to the less pertinent contextual cues (see Garcia and Jaffard 1996
). Accordingly, the presently observed blockade of induction of lateral septal LTP would prevent (or slow down) subsequent instrumental learning tasks using discrete unimodal CS predictive of the occurrence of the US (i.e., "learned helplessness") (Maier and Seligman 1976
; Overmaier and Seligman 1967
). Along with this assumption, adding a CS that is consistently paired with the US to the protocol we have presently used should release lateral septal LTP from blockade. Although this possibility remains to be directly tested, it seems congruent with previous experiments showing that signaled FSs preclude the occurence of subsequent impairment of escape learning (Jackson and Minor 1988
), and it is reminiscent of previous experiments conducted by Shors et al. (1989)
showing that inescapable but not escapable shocks block LTP in the rat hippocampus. Beyond the fact that this phenomenon was described in the Schaffer collateral-CA1 hippocampal synapses, there are, nevertheless, important differences between the findings of Shors et al. and our present data. First, LTP was measured in vitro in hippocampal slices so that the observed blockade of LTP induction was clearly not related to contextual conditioning as presently demonstrated. Second, because subjects were not presented with a CS before the occurrence of the shock US, it may only be assumed that the controlability and not the predictibility of the US modulates subsequent synaptic plasticity.
In conclusion, the present experiment shows that contextual conditioned fear blocks the induction of LTP by high-frequency electrical stimulation in the LS. Because previous experiments have shown that these synapses exhibit long-lasting changes in efficacy that are associated with the rate of acquisition of certain learning tasks (i.e., "behavioral LTP/LTD"), this phenomenon offers a unique opportunity to identify the specific conditions in which a stressful stimulus may produce a detrimental effect on learning, via concomitant alterations in training-induced changes in synaptic efficacy in the LS. Experiments aimed at testing this hypothesis are currently in progress. More widely, the present results again emphasize the functional importance of plasticity of LS glutamatergic synapses, the alteration of which (see also Garcia and Jaffard 1993
) may compromise, through impaired feedback regulation of hippocampal activity, specific learning and memory processes (see Jaffard et al. 1996
).
 |
ACKNOWLEDGEMENTS |
We thank Dr. T. P. Durkin for helpful comments on the manuscript.
This work was supported by the Centre National de la Recherche Scientifique and by the Conseil Régional d'Aquitaine.
 |
FOOTNOTES |
Address reprint requests to R. Garcia.
Received 18 October 1996; accepted in final form 18 March 1997.
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REFERENCES |
-
DE WIED, D.
The effects of neurohypophyseal hormones and related peptides on learning and memory processes.
In: Peripheral Signalling of the Brain,
edited by
R.C.A. Frederickson,
J. L. McGaugh,
and D. L. Felten
. Toronto: Hogreffe and Huber, 1991, p. 335-350
-
DIAMOND, D. M.,
BENNETT, M. C.,
STEVENS, K. E.,
WILSON, R. L.,
ROSE, G. M.
Exposure to a novel environment interferes with the induction of hippocampal primed burst potentiation.
Psychobiology
18: 273-281, 1990.
-
ENGELMAN, M.,
LUDWIG, M.,
LANDGRAF, R.
Microdialysis administration of vasopressin and vasopressin antagonists into the septum during pole-jumping behavior.
Bevav. Neural Biol.
58: 51-57, 1992.
-
GARCIA, R.,
JAFFARD, R.
The hippocampo-septal projection in mice: long-term potentiation in the lateral septum.
Neuroreport
3: 193-196, 1992.[Medline]
-
GARCIA, R.,
JAFFARD, R. A
comparative study of age-related changes in inhibitory processes and long-term potentiation in the lateral septum of mice.
Brain Res.
620: 229-236, 1993.[Medline]
-
GARCIA, R.,
JAFFARD, R.
Changes in synaptic excitability in the lateral septum associated with contextual and auditory fear conditioning in mice.
Eur. J. Neurosci.
8: 809-815, 1996.[Medline]
-
GARCIA, R.,
TOCCO, G.,
BAUDRY, M.,
THOMPSON, R. F.
Polysynaptic potentiation in the lateral septum following stimulation of the fimbria in anesthetized rats.
Brain Res.
737: 169-174, 1996.[Medline]
-
GARCIA, R.,
VOUIMBA, R. M.,
JAFFARD, R.
Spatial discrimination learning induces LTP-like changes in the lateral septum of mice.
Neuroreport
5: 329-332, 1993.[Medline]
-
GARCIA, R.,
VOUIMBA, R. M.,
JAFFARD, R.
Differential effects of spatial reference and working memory testing on synaptic efficacy in the lateral septum of mice.
Soc. Neurosci. Abstr.
19: 376, 1995.
-
GRANT, S.G.N.,
O'DELL, T. J.,
KARL, K. A.,
STEIN, P. L.,
SORIANO, P.,
KANDEL, E. R.
Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.
Science Wash. DC
258: 1903-1910, 1992.[Medline]
-
JACKSON, R. L.,
MINOR, T. L.
Effects of signaling the inescapable shock on subsequent escape learning: implications for theories of coping and "learned helplessness."
J. Exp. Psychol. Anim. Behav. Processes
14: 390-400, 1988.[Medline]
-
JAFFARD, R.,
VOUIMBA, R. M.,
MARIGHETTO, A.,
GARCIA, R.
Long-term potentiation and long-term depression in the lateral septum in spatial working and reference memory.
J. Physiol. Paris
90: 339-341, 1996.[Medline]
-
JOËLS, M.,
AND URBAN, I.J.A.
Amino acid neurotransmission between fimbria-fornix fibers and neurons in the lateral septum of the rat: a microiontophoretic study.
Exp. Neurol.
84: 126-139, 1984.[Medline]
-
LYNCH, G.,
BAUDRY, M.
The biochemistry of memory: a new specific hypothesis.
Science Wash. DC
224: 1057-1063, 1984.[Medline]
-
MAIER, S. F.,
SELIGMAN, M.E.P.
Learned helplessness: theory and evidence.
J. Exp. Psychol. Gen.
105: 3-45, 1976.
-
MARTINEZ, J. L.,
DERRICK, B. E.
Long-term potentiation and learning.
Annu. Rev. Psychol.
47: 173-203, 1996.[Medline]
-
MCLENNAN, H.,
MILLER, J. J.
The hippocampal control of neuronal discharges in the septum of the rat.
J. Physiol. Lond.
237: 607-624, 1974.[Medline]
-
MORRIS, R.G.M.,
ANDERSON, E.,
LYNCH, G. S.,
BAUDRY, M.
Selective impairment of learning and blockade of long-term potentiation of a N-methyl-D-aspartate receptor antagonist, AP5.
Nature Lond.
319: 774-776, 1986.[Medline]
-
OVERMAIER, J. B.,
SELIGMAN, M.E.P.
Effects of inescapable schock upon subsequent escape and avoidance responding.
J. Comp. Physiol. Psychol.
63: 28-33, 1967.[Medline]
-
RACINE, R. J.,
MILGRAM, N. W.,
HAFNER, S.
Long-term potentiation phenomena in the rat limbic forebrain.
Brain Res.
260: 217-231, 1983.[Medline]
-
RAISMAN, G.
An experimental analysis of the efferent projection of the hippocampus.
Brain
89: 83-108, 1966.[Medline]
-
SHORS, T. J.,
SEIB, T. B.,
LEVINE, S.,
THOMPSON, R. F.
Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus.
Science Wash. DC
244: 224-226, 1989.[Medline]
-
STAIGER, J. F. AND NÜRNBERGER, F. Pattern of afferents to the lateral septum in the guinea pig, Cell Tissue Res. 257: 471-490, 1989.
-
STAUBLI, U.,
THIBAULT, O.,
DILORENZO, M.,
LYNCH, G.
Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory.
Behav. Neurosci.
103: 54-60, 1989.[Medline]
-
SILVA, A. J.,
STEVENS, C. F.,
TONEGA, S.,
WANG, Y.
Deficient hippocampal long-term potentiation in calcium/calmodulin kinase II mutant mice.
Science Wash. DC
257: 201-206, 1992.[Medline]
-
STORM-MATHISEN, J.,
WOXEN-OPSAHL, M.
Aspartate and/or glutamate may be transmitters in hippocampal efferents to septum and hypothalamus.
Neurosci. Lett.
9: 65-70, 1978.
-
SWANSON, L. W.,
COWAN, W. M.
The connections of the septal region in the rat.
J. Comp. Neurol.
186: 621-656, 1979.
-
TEYLER, T. J.,
DISCENNA, P.
Long-term potentiation as a candidate mnemonic device.
Brain Res. Rev.
7: 17-28, 1984.
-
THOMAS, E.
Forebrain mechanisms in the relief of fear: the role of the lateral septum.
Psychobiology
16: 36-44, 1988.
-
THOMAS, E.,
YADIN, E.,
STRICKLAND, C. E.
Septal unit activity during classical conditioning: a regional comparison.
Brain Res.
547: 303-308, 1991.[Medline]
-
URBAN, I.J.A.,
ONTSKUL, A.,
CROISET, G.,
CHENG, Y.,
DE WIED, D. A.
Long-lasting increase and decrease in synaptic excitability in the rat lateral septum are associated with high and low shuttle box performance, respectively.
Behav. Brain Res.
68: 173-183, 1995.[Medline]
-
VAN DEN HOOFF, P.,
URBAN, I.J.A.,
DE WIED, D.
Vasopressin maintains long-term potentiation in rat lateral septum slices.
Brain Res.
505: 181-186, 1989.[Medline]
-
WARREN, D. A.,
CASTRO, C. A.,
RUDY, J. W.,
MAIER, S. F.
No spatial learning impairment following exposure to inescapable shock.
Psychobiology
19: 127-134, 1991.
-
ZACZEK, R.,
HEDREEN, J. C.,
COYLE, J. T.
Evidence for a hippocampal-septal glutamatergic pathway in the rat.
Exp. Neurol.
65: 145-156, 1979.[Medline]