The Role of CA3 Hippocampal NMDA Receptors in Paired Associate Learning

Rajji, Tarek K.; Chapman, David; Eichenbaum, Howard; Greene, Robert

doi:10.1523/jneurosci.4194-05.2006

Cited by 96 publications

(102 citation statements)

References 38 publications

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“…This involved unilateral infusion of an adenoassociated virus vector for Cre recombinase (AAV-Cre), into our mice, in which the gene for the NMDA receptor essential subunit NR1 was ''floxed'' (fNR1 mice). This approach, which minimizes potential developmental effects of the gene deletion, has been shown to cause a selective, functional removal of NMDAr-mediated synaptic transmission and plasticity, and a behavioral deficit in new learning in a paired associate task (Rajji et al, 2006). We observed that infusion of AAV-Cre into CA3 completely blocked the novelty-enhancement of beta2 oscillations (Fig.…”

Section: Ca3 Nmda Receptors Are Required For Novelty-evoked Oscillationsmentioning

confidence: 63%

“…In addition, the widespread connections of interneuron networks play a critical role in synchronizing oscillatory activity throughout hippocampus (Buzsáki, 2006). Altered NMDA function in interneuron populations with divergent connections may explain why we observed a substantial decrease in beta2 oscillations in both CA1 and CA3, following a viral manipulation that disrupted NMDA receptors in only a limited portion of the septo-temporal extent of CA3 (10-30%; Rajji et al, 2006). The same viral manipulation, when given bilaterally, is sufficient to disrupt new learning (Rajji et al, 2006).…”

Section: Discussionmentioning

confidence: 87%

“…Altered NMDA function in interneuron populations with divergent connections may explain why we observed a substantial decrease in beta2 oscillations in both CA1 and CA3, following a viral manipulation that disrupted NMDA receptors in only a limited portion of the septo-temporal extent of CA3 (10-30%; Rajji et al, 2006). The same viral manipulation, when given bilaterally, is sufficient to disrupt new learning (Rajji et al, 2006). Our observations suggest that, in addition to their better-characterized role gating calcium entry to affect local synaptic strength, CA3 NMDA receptors may contribute to learning via an influence over circuit-and systems-level dynamics.…”

Section: Discussionmentioning

confidence: 87%

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Transient 23–30 Hz oscillations in mouse hippocampus during exploration of novel environments

et al. 2008

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ABSTRACT:The hippocampus is a key brain structure for the encoding of new experiences and environments. Hippocampal activity shows distinct oscillatory patterns, but the relationships between oscillations and memory are not well understood. Here we describe bursts of hippocampal 23-30 Hz (beta2) oscillations in mice exploring novel, but not familiar, environments. In marked contrast to the relatively invariant 8 Hz theta rhythm, beta2 power was weak during the very first lap of the novel environment, increased sharply as the mice reencountered their start point, then persisted for only a few minutes. Novelty-evoked oscillations reflected precise synchronization of individual neurons, and participating pyramidal cells showed a selective enhancement of spatial specificity. Through focal viral manipulations, we found that novelty-evoked oscillations required functional NMDA receptors in CA3, a subregion critical for fast oscillations in vitro. These findings suggest that beta2 oscillations indicate a hippocampal dynamic state that facilitates the formation of unique contextual representations. V

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Section: Ca3 Nmda Receptors Are Required For Novelty-evoked Oscillationsmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 87%

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Transient 23–30 Hz oscillations in mouse hippocampus during exploration of novel environments

et al. 2008

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“…The CA3 region of the dorsal hippocampus is preferentially associated with acquisition, whereas the CA1 region is associated with retrieval of contextual fear memory (Lee and Kesner, 2004). Furthermore, studies suggest that it is the NMDA receptors in the CA3 region, particularly in the dorsal hippocampus, that are involved in the rapid, onetrial encoding of complex associations between contextual stimuli (Cravens et al, 2006;Rajji et al, 2006).…”

Section: Estrone and Estradiol Increase Synaptophysin Expression In Tmentioning

confidence: 99%

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

Barha

Dalton

Galea

2009

Neuropsychopharmacol

108

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Estrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. In particular, 17b-estradiol can improve, impair, or have no effect on hippocampus-dependent learning and memory depending on dose and time of administration. The effects of other forms of estrogen, such as estrone and 17a-estradiol, on hippocampus-dependent learning have not been as thoroughly investigated. Therefore, the purpose of this study was to investigate the effects of 17b-estradiol, estrone, and 17a-estradiol at three different doses on two different tasks: hippocampus-dependent contextual fear conditioning and hippocampusindependent cued fear conditioning. Adult ovariectomized female rats were injected with one of the estrogens at one of the three doses 30 mins before conditioning to assess the rapid effects of these estrogens on acquisition. Twenty-four hours later memory for the context was examined and 1 h later memory for the cue (tone) was assessed. Levels of synaptophysin were examined in the dorsal hippocampus of rats to identify a potential synaptic correlate of hormonal effects on contextual fear conditioning. Low 17b-estradiol and 17a-estradiol enhanced, whereas high 17b-estradiol and 17a-estradiol impaired, contextual fear conditioning. Only the middle dose of estrone severely impaired contextual fear conditioning. Estrogens did not alter performance in the hippocampus-independent cued task. Synaptophysin expression was increased by estrone (at a middle and high dose) and 17b-estradiol (at a middle dose) in the CA3 region of the hippocampus and was not correlated with cognition. The results of this study indicate that estradiol can positively or negatively influence hippocampus-dependent learning and memory, whereas estrone impairs hippocampus-dependent learning and memory in a dose-dependent manner. These results have important therapeutic implications, as estrone, a main component of a widely used hormone replacement therapy, was shown to have either a negative effect or no effect on learning and memory. It may be possible to use 17a-estradiol and lower doses of estrogens as potential alternatives in hormone replacement therapies.

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“…In this study, animals learned which of two stimulus items (what) was rewarded depending on the environmental context (where) in which the items were presented (Rajji et al 2006;Manns and Eichenbaum 2009). On each trial, a rat initially explored one of the two contexts, after which the two stimulus items were placed into different positions (corners) of the context (Fig.…”

mentioning

confidence: 99%

A mechanism for the formation of hippocampal neuronal firing patterns that represent what happens where

Tort¹,

Komorowski²,

Eichenbaum³

2011

Learn. Mem.

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The association of specific events with the context in which they occur is a fundamental feature of episodic memory. However, the underlying network mechanisms generating what-where associations are poorly understood. Recently we reported that some hippocampal principal neurons develop representations of specific events occurring in particular locations (item-position cells). Here, we investigate the emergence of item-position selectivity as rats learn new associations for reward and find that before the animal's performance rises above chance in the task, neurons that will later become itemposition cells have a strong selective bias toward one of two behavioral responses, which the animal will subsequently make to that stimulus. This response bias results in an asymmetry of neural activity on correct and error trials that could drive the emergence of particular item specificities based on a simple reward-driven synaptic plasticity mechanism.The hippocampus is critically involved in the acquisition of new episodic memories (Scoville and Milner 1957;Eichenbaum 2000). In particular, the formation of associations between events and the context where they occur, a fundamental feature of episodic memory, depends on hippocampal function (Manns and Eichenbaum 2006;Eichenbaum et al. 2007).We have recently shown that some hippocampal principal neurons develop representations of specific events occurring in particular locations (Komorowski et al. 2009). In this study, animals learned which of two stimulus items (what) was rewarded depending on the environmental context (where) in which the items were presented (Rajji et al. 2006;Manns and Eichenbaum 2009). On each trial, a rat initially explored one of the two contexts, after which the two stimulus items were placed into different positions (corners) of the context (Fig. 1A); the animal then investigated the items (scented flower pots), and should learn to dig (Go response) for a buried food reward in the appropriate pot for that context or not dig (NoGo) at pots where no reward was buried. All animals performed at no better than chance (50%) for the first 30 trials, then acquired the what-where associations, reaching an average accuracy of 86% in the last 30 trials of the training session (Fig. 1B).In this paradigm, we previously indentified principal neurons showing differential firing during the sampling of one of the two stimulus items when located in the same position (Fig. 1C, left), which we called as item-position (IP) cells (Komorowski et al. 2009). IP cell responses did not distinguish the items during the first 30 trials of the learning session, but did fire during item sampling at particular locations. Subsequently, we showed that many IP cells increased firing during the sampling of an item-position combination in parallel with learning (Fig. 1C, left). Importantly, we observed approximately equivalent selectivity for rewarded and nonrewarded item-position combinations (Fig. 1C, middle). We also identified principal neurons that were active during item sampl...

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The Role of CA3 Hippocampal NMDA Receptors in Paired Associate Learning

Cited by 96 publications

References 38 publications

Transient 23–30 Hz oscillations in mouse hippocampus during exploration of novel environments

Transient 23–30 Hz oscillations in mouse hippocampus during exploration of novel environments

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

A mechanism for the formation of hippocampal neuronal firing patterns that represent what happens where

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