Evidence for a specific integrative mechanism for episodic memory mediated by AMPA/kainate receptors in a circuit involving medial prefrontal cortex and hippocampal CA3 region
Abstract
We asked whether episodic-like memory requires neural mechanisms independent of those that mediate its component memories for "what," "when," and "where," and if neuronal connectivity between the medial prefrontal cortex (mPFC) and the hippocampus (HPC) CA3 subregion is essential for episodic-like memory. Unilateral lesion of the mPFC was combined with unilateral lesion of the CA3 in the ipsi- or contralateral hemispheres in rats. Episodic-like memory was tested using a task, which assesses the integration of memories for "what, where, and when" concomitantly. Tests for novel object recognition (what), object place (where), and temporal order memory (when) were also applied. Bilateral disconnection of the mPFC-CA3 circuit by N-methyl-d-aspartate (NMDA) lesions disrupted episodic-like memory, but left the component memories for object, place, and temporal order, per se, intact. Furthermore, unilateral NMDA lesion of the CA3 plus injection of (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX) (AMPA/kainate receptor antagonist), but not AP-5 (NMDA receptor antagonist), into the contralateral mPFC also disrupted episodic-like memory, indicating the mPFC AMPA/kainate receptors as critical for this circuit. These results argue for a selective neural system that specifically subserves episodic memory, as it is not critically involved in the control of its component memories for object, place, and time.
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Episodic-like memory is not simply a combination of what, where and when memories, but a meta-system which integrates these three components into a complex and distinct compound system.
“Based on the experimental model, episodic-like memory has been found to be not simply a combination of “what”, “where” and “when” memories, but a meta-system which integrates these three components into a complex and distinct compound system (de Souza Silva et al., 2016).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as de Souza Silva et al., 2016
The counterintuitive result OS > OD indicates that the exploration pattern of objects according to their location is influenced by the temporal-order in which they were experienced.
“This counterintuitive result (OS > OD) indicates that the exploration pattern of objects according to their location is influenced by the temporal-order in which they have been experienced in the past (Chao et al., 2016a; Chao et al., 2017; de Souza Silva et al., 2016; Drieskens et al., 2017)”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as de Souza Silva et al., 2016
Disconnecting the PFC-CA3 circuit impaired performance in the ELM2-2 test, but did not interfere with performance in the individual NOP, OPP and TOM tests.
“By contrast, disconnecting the PFC-CA3 circuit also impaired performance in the ELM2–2 test, but did not interfere with performance in the individual NOP, OPP and TOM tests.”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as de Souza Silva et al., 2016
Pharmacological inactivation of the PFC in one hemisphere with CNQX, but not with AP-5, combined with lesions of CA3 in the opposite hemisphere disrupted episodic-like memory.
“Pharmacological inactivation of the PFC in one hemisphere with CNQX, but not with AP-5, combined with lesions of CA3 in the opposite hemisphere (disconnecting the CA3 and PFC gultamatergic circuit) disrupted episodic-like memory (de Souza Silva et al., 2016).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as de Souza Silva et al., 2016
Different extents of episodic-like memory deficits were observed depending on the region disconnected in studies disconnecting the mPFC from CA1, CA3 or LEC.
“Different extents of episodic-like memory deficits were observed, depending on the region disconnected in the studies of disconnecting the mPFC either from the CA1, CA3 or LEC (Chao et al., 2016a; Chao et al., 2017; de Souza Silva et al., 2016) (Table 5).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as de Souza Silva et al., 2016
When the PFC-CA3 pathway was disconnected, the interaction, as well as the where and when indexes were disrupted.
“When the PFC-CA3 pathway was disconnected, the interaction, as well as the where and when indexes were disrupted.”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as de Souza Silva et al., 2016
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Chao, O. Y., de Souza Silva, M. A., Yang, Y.-M., & Huston, J. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.007 · Cited by 158 · see citing works
Self-citationChao, O. Y., Nikolaus, S., Lira Brandão, M., Huston, J. P., & de Souza Silva, M. A. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.03.019 · Cited by 38 · see citing works
Self-citationCA1 inactivation impairs episodic-like memory in rats
Drieskens, D. C., Neves, L. R., Pugliane, K. C., de Souza, I. B. M. B., Lima, Á. D. C., Salvadori, M. G. D. S. S., Ribeiro, A. M., Silva, R. H., & Barbosa, F. F. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.08.008 · Cited by 31 · see citing works
- Authors
- de Souza Silva, M. A., Huston, J. P., Wang, A.-L., Petri, D., & Chao, O. Y.-H.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-06-05
- Volume
- 26
- Issue
- 7
- Pages
- 3000-3009
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2308904057
- Cited by
- 41
- References
- 66
- Citations by year
- 2026: 2 · 2024: 3 · 2022: 5 · 2021: 2 · 2020: 8 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 4
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- episodic-like memory, medial prefrontal cortex, hippocampal CA3, non-NMDA receptors, NMDA lesions, CNQX, novel object recognition, temporal order memory, memory integration
- MeSH terms
- Animals, Exploratory Behavior, Male, Neural Pathways, Time Perception, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Rats, Wistar, Prefrontal Cortex, Receptors, AMPA, Kainic Acid Receptors, Receptors, Kainic Acid, Neurotransmitter Agents, Recognition, Psychology, CA3 Region, Hippocampal, Memory, Episodic
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