title: 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.
authors.affiliation: Center for Behavioral Neuroscience, University of Düsseldorf, Düsseldorf 40225, Germany.
authors.forename: Maria A
authors.initials: MA
authors.lastname: de Souza Silva
authors.affiliation: Center for Behavioral Neuroscience, University of Düsseldorf, Düsseldorf 40225, Germany.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Huston
authors.affiliation: Center for Behavioral Neuroscience, University of Düsseldorf, Düsseldorf 40225, Germany.
authors.forename: An-Li
authors.initials: AL
authors.lastname: Wang
authors.affiliation: Center for Behavioral Neuroscience, University of Düsseldorf, Düsseldorf 40225, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Petri
authors.affiliation: Center for Behavioral Neuroscience, University of Düsseldorf, Düsseldorf 40225, Germany.
authors.forename: Owen Yuan-Hsin
authors.initials: OY
authors.lastname: Chao
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D061212:Memory, Episodic; D016202:N-Methylaspartate / Q000378:metabolism / Q000633:toxicity; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013998:Time Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D016202:N-Methylaspartate; D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate
keywords: AMPA receptor; CA3; NMDA receptor; episodic-like memory; medial prefrontal cortex