Spatial learning without NMDA receptor-dependent long-term potentiation

Saucier, Deborah M.; Cain, Donald P.

doi:10.1038/378186a0

Cited by 307 publications

(274 citation statements)

References 21 publications

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“…Perceptual learning, which can refer to a learned change in the salience and discriminability of a stimulus, is a well-documented and widespread consequence of stimulus exposure, and it profoundly alters how a subject learns about the CS during subsequent conditioning (Hall, 1991). These results are consistent with studies from spatial learning (Bannerman et al, 1995;Saucier & Cain, 1995;Saucier et al, 1996), Pavlovian contextual fear conditioning (Sanders & Fanselow, 2003) and one-trial inhibitory avoidance learning (Roesler et al, 1998), showing that the preexposure to the stimuli or actions to be learned about can determine the effects of NMDA receptor antagonism on later learning. In the case of fear extinction, the present results raise the question: What aspect of fearextinction learning do NMDA receptor antagonists normally disrupt?…”

Section: Discussionsupporting

confidence: 78%

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Chan

McNally

2009

Behavioral Neuroscience

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Six experiments studied the role of conditioned stimulus (CS) familiarity in determining the effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on fear extinction. Systemic administration of MK-801 (0.1 mg/kg) impaired initial extinction but not reextinction learning. MK-801 impaired reextinction learning when the CS was relatively novel during reextinction training but not initial extinction learning when the CS was relatively familiar during initial extinction training. A context change failed to reinstate the sensitivity of initial fear extinction learning about a relatively familiar CS to MK-801. These experiments show that CS familiarity is an important determinant of effects of MK-801 on fear extinction learning: MK-801 impaired extinction learning about novel stimuli but spared extinction learning about familiar stimuli.

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Section: Discussionsupporting

confidence: 78%

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Chan

McNally

2009

Behavioral Neuroscience

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“…However, it was found recently that either pretraining or pre-exposure to the task apparatus could prevent the amnesia induced by intrahippocampal infusion of AP5 (Roesler et al 1998). This resembles the finding that both nonspatial (Saucier and Cain 1995) and spatial (Bannerman et al 1995) pretraining prevent the impairing effect of NMDA receptor antagonists on spatial recall of the Morris water maze, a task that depends on the hippocampus. This observation led Morris and colleagues to speculate that the amnestic effect of the NMDA blockers was more a response to novelty than to the specificity of the task per se.…”

Section: Introductionmentioning

confidence: 53%

Two Time Windows of Anisomycin-Induced Amnesia for Inhibitory Avoidance Training in Rats: Protection from Amnesia by Pretraining but not Pre-exposure to the Task Apparatus

et al. 1999

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We have studied the effect of training conditions on hippocampal protein synthesis-dependent processes in consolidation of the inhibitory avoidance task. Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.4 mA foot shock, 24 hr training-test interval). Fifteen minutes before or 0, 3, or 6 hr after training, animals received a 0.8-µl intrahippocampal infusion of the protein-synthesis inhibitor anisomycin (80 µg) or vehicle (PBS, pH 7.4). The infusion of anisomycin impaired retention test performance in animals injected 15 min before and 3 hr after the training session, but not at 0 or 6 h post-training. Pretraining with a low foot shock intensity (0.2 mA) 24 hr before training, prevented the amnestic effect of anisomycin injected at 15 min before or 3 hr after training. However, simple pre-exposure to the inhibitory avoidance apparatus did not alter the amestic effects of anisomycin. The results suggest that hippocampal protein synthesis is critical in two periods, around the time of, and 3 hr after training. A prior weak training session, however, which does not itself alter step-down latencies, is sufficient to prevent the amnestic effect of anisomycin, suggesting that even if not behaviorally detectable, weak training must be sufficient to produce some lasting cellular expression of the experience.

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“…It has been shown, for example, that standard water maze performance is not disturbed by N-methyl-D-aspartate (NMDA) receptor antagonists (37,38), but that the delayed-matching-to place (DMP) task in the water maze is impaired at long (20 min) but not short (15 s) delays (16). If this explanation is correct, then temporary inactivation of one hippocampus should impair DMP at long delays too.…”

Section: Discussionmentioning

confidence: 99%

Inactivating one hippocampus impairs avoidance of a stable room-defined place during dissociation of arena cues from room cues by rotation of the arena

Cimadevilla

Wesierska

Fenton

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

150

136

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Unilateral intrahippocampal injections of tetrodotoxin were used to temporarily inactivate one hippocampus during specific phases of training in an active allothetic place avoidance task. The rat was required to use landmarks in the room to avoid a room-defined sector of a slowly rotating circular arena. The continuous rotation dissociated room cues from arena cues and moved the arena surface through a part of the room in which foot-shock was delivered. The rat had to move away from the shock zone to prevent being transported there by the rotation. Unilateral hippocampal inactivations profoundly impaired acquisition and retrieval of the allothetic place avoidance. Posttraining unilateral hippocampal inactivation also impaired performance in subsequent sessions. This allothetic place avoidance task seems more sensitive to hippocampal disruption than the standard water maze task because the same unilateral hippocampal inactivation does not impair performance of the variable-start, fixed hidden goal task after procedural training. The results suggest that the hippocampus not only encodes allothetic relationships amongst landmarks, it also organizes perceived allothetic stimuli into systems of mutually stable coordinates. The latter function apparently requires greater hippocampal integrity.T he rodent hippocampus is a key neural system for processing information about the current spatial arrangement of stimuli and events (1-4), but it is still unclear what spatial computations the hippocampus actually does. One direction of the current experimental effort in this area is studying what aspects of spatial information the hippocampal network stores (5-12); a second is studying what spatial computations an intact hippocampal system is necessary for (13)(14)(15)(16)(17)(18)(19).It is crucial for this latter approach that there are behavioral paradigms, with clearly defined demands, that subjects must solve by using a limited set of potential solutions. The standard, variable-start, fixed hidden goal place navigation task in the water maze (20) has been invaluable because it allows the optimal solution to be readily distinguished from other less efficient strategies. The optimal strategy is for the rat to learn the allothetic relationships between distant, typically visual stimuli and the position of the escape platform. The absence of stable stimuli on the liquid substrate, like visual and tactile marks and odor cues, and the use of variable start locations make it difficult after standard training for the rat to solve the task optimally by using beacon-guided, praxis, or route-following strategies.Since the early eighties, place learning in the water maze has been used in lesion studies to elucidate the role of the hippocampus in spatial cognition (21,22). Selective bilateral lesions of the dentate gyrus and CA3-CA4 were found to severely impair water maze performance (23). However, in that study, unilateral dentate gyrus lesions, but not CA3-CA4 lesions disturbed water maze performance.One difficulty in interpreting t...

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Spatial learning without NMDA receptor-dependent long-term potentiation

Cited by 307 publications

References 21 publications

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Two Time Windows of Anisomycin-Induced Amnesia for Inhibitory Avoidance Training in Rats: Protection from Amnesia by Pretraining but not Pre-exposure to the Task Apparatus

Inactivating one hippocampus impairs avoidance of a stable room-defined place during dissociation of arena cues from room cues by rotation of the arena

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