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.

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.

The interaction between the dopaminergic forebrain projections and the medial prefrontal cortex is critical for memory of objects: implications for Parkinson's disease.

Neuropsychological and neuroimaging studies have implicated the dopaminergic nigrostriatal pathway and the prefrontal cortex in learning and memory deficits in patients with Parkinson's disease. However, little is known about how these two brain regions interact in the processing of learning and memory. We employed a disconnection procedure to test whether interaction of these regions contributes to performance in various memory tasks. Male rats received either a unilateral injection of 6-hydroxydopamine into the nigro-striatal tract or a unilateral NMDA lesion in the medial prefrontal cortex, or both these lesions combined in either the same or opposite hemispheres. Spontaneous object exploration, spatial working memory, locomotor, emotional and sensorimotor tests were administered. Only the group with both lesions placed in opposite hemispheres failed to show object recognition memory. None of the groups treated with 6-hydroxydopamine showed intact temporal order memory, whereas only the groups that received combined lesions failed to show object-in-place and spatial recognition memory. No differences between groups were found in the spatial working memory test. Our data indicate that locomotor, emotional and sensorimotor factors are not likely to confound the results of the memory tests. Thus, the interaction between the dopaminergic forebrain projections, particularly the nigrostriatal dopamine, and the medial prefrontal cortex is critical for object recognition memory but not for spatial working memory in rats.