Hippocampal CA3 NMDA Receptors Are Crucial for Memory Acquisition of One-Time Experience

Nakazawa, Kazu; Sun, Lillian; Quirk, Michael C.; Rondi-Reig, Laure; Wilson, Matthew A.; Tonegawa, Susumu

doi:10.1016/s0896-6273(03)00165-x

Cited by 444 publications

(408 citation statements)

References 39 publications

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“…accordance with evidence that demonstrate the importance of this structure in the rapid acquisition of new information (Nakazawa et al 2003;Leutgeb et al 2006;Miyashita et al 2009). In our task, the odor combination in a paired associate is session unique (see Materials and Methods).…”

Section: Discussionsupporting

confidence: 87%

Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events

Farovik¹,

Dupont²,

Eichenbaum³

2009

Learn. Mem.

128

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Previous studies have suggested that dorsal hippocampal areas CA3 and CA1 are both involved in representing sequences of events that compose unique episodes. However, it is uncertain whether the contribution of CA3 is restricted to spatial information, and it is unclear whether CA1 encodes order per se or contributes by an active maintenance of memories of sequential events. Here, we developed a new behavioral task that examines memory for the order of sequential nonspatial events presented as trial-unique odor pairings. When the interval between odors within a studied pair was brief (3 sec), bilateral dorsal CA3 lesions severely disrupted memory for their order, whereas dorsal CA1 lesions did not affect performance. However, when the inter-item interval was extended to 10 sec, CA1 lesions, as well as CA3 lesions, severely disrupted performance. These findings suggest that the role of CA3 in sequence memory is not limited to spatial information, but rather appears to be a fundamental property of CA3 function. In contrast, CA1 becomes involved when memories for events must be held or sequenced over long intervals. Thus, CA3 and CA1 are both involved in memory for sequential nonspatial events that compose unique experiences, and these areas play different roles that are distinguished by the duration of time that must be bridged between key events.Episodic memory involves the ability to encode and retrieve the order of events in individual experiences (Tulving 1983). Recent evidence in both animals and humans indicates that the hippocampus plays a critical role in this capacity. In animals, damage to the hippocampus impairs memory for the order of associated elements that compose an episode Kesner et al. 2002), and hippocampal neuronal activity reflects processing of the order of events in both spatial (Dragoi and Buzsáki 2006;Foster and Wilson 2007) and nonspatial episodes (Manns et al. 2007). In humans, hippocampal activation has also been related to memory for the order of elements (Kumaran and Maguire 2006;Lehn et al. 2009;Ross et al. 2009).Within the hippocampal circuitry, contributions of the CA3 and CA1 fields are probably most extensively studied, but this work has not yet clarified the distinct roles of these areas in sequence memory. Computational models suggest that the recurrent connections of CA3 cells operate as an attractor network that computes associations between elements (Norman and O'Reilly 2003;Rolls 2007) and is suitable for representing sequences of events in episodic memories (Jensen and Lisman 1996;Levy 1996;Lisman 1999). Studies on the effects of selective damage within the hippocampus have shown that CA3 is critical for remembering sequences of spatial locations (Hunsaker et al. 2008a), but not sequences of nonspatial events (Hoge and Kesner 2007). It is, therefore, uncertain whether CA3 is critical for sequence memory per se, rather than other aspects of spatial processing. Other observations suggest that CA1 may be involved in memory for the order of both spatial (Hunsaker et al. 2008a)...

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Section: Discussionsupporting

confidence: 87%

Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events

Farovik¹,

Dupont²,

Eichenbaum³

2009

Learn. Mem.

128

View full text Add to dashboard Cite

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“…Similar results were obtained with CA3-specific neurotoxic lesions (Lee and Kesner 2003). Nakazawa et al (2003) reported similar findings with a mouse strain in which the function of CA3 NMDA receptors was disrupted. These mutant mice were impaired in learning a novel platform location in a modified water maze task, whereas they were normal in finding familiar platform locations.…”

supporting

confidence: 82%

Disconnection analysis of CA3 and DG in mediating encoding but not retrieval in a spatial maze learning task

Jerman¹,

Kesner²,

Hunsaker³

2006

Learn. Mem.

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The dentate gyrus (DG) subregion of the hippocampus has been shown to be involved in encoding but not retrieval in a spatial maze task (modified Hebb-Williams maze). The first experiment in this study examined whether a lesion to the CA3 would contribute to a similar encoding deficit. A DG group was included in order to replicate previous results. Relative to controls, animals receiving CA3 lesions were impaired in encoding, not retrieval, on the modified Hebb-Williams maze-similar to a group that received DG lesions. This suggests the possibility that CA3 and DG are working together to mediate encoding processes. The second experiment in this study was designed to test the interaction between CA3 and DG using a disconnection paradigm. Animals with contralateral lesions (CA3 lesioned in one hemisphere, DG lesioned in the other hemisphere) showed a significant disruption effect on encoding, but not retrieval, when compared with animals with ipsilateral lesions (CA3 and DG lesioned in the same hemisphere, leaving the other hemisphere intact). This suggests an interaction between CA3 and DG in supporting encoding but not retrieval processes in a spatial maze learning task.

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“…The MECIII cells and Island cells appear less important for spatial contextual memory. Instead, the hippocampal CA3 region may be crucial for the formation of spatial contextual memory (Nakazawa et al 2003;Nakashiba et al 2008). Thus, the trisynaptic pathway from Ocean cells in ECII to CA1 via the trisynaptic circuit may primarily process spatial context, whereas the direct pathways from MECIII and Island-SL-INs may be responsible for temporal properties of episodic memory.…”

Section: Discussionmentioning

confidence: 99%

Entorhinal–hippocampal neuronal circuits bridge temporally discontiguous events

2015

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The entorhinal cortex (EC) -hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits subserving the temporal dimension are just beginning to be understood. In this review, we examine the evidence concerning the role of the EC in associating events separated by time-or temporal associative learning-with emphasis on the function of persistent activity in the medial entorhinal cortex layer III (MECIII) and their direct inputs into the CA1 region of HPC. We also discuss the unique role of Island cells in the medial entorhinal cortex layer II (MECII), which is a newly discovered direct feedforward inhibitory circuit to CA1. Finally, we relate the function of these entorhinal cortical circuits to recent findings concerning hippocampal time cells, which may collectively activate in sequence to bridge temporal gaps between discontiguous events in an episode.

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Hippocampal CA3 NMDA Receptors Are Crucial for Memory Acquisition of One-Time Experience

Cited by 444 publications

References 39 publications

Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events

Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events

Disconnection analysis of CA3 and DG in mediating encoding but not retrieval in a spatial maze learning task

Entorhinal–hippocampal neuronal circuits bridge temporally discontiguous events

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