Excitatory Amino Acid Pathway from the Hippocampus to the Prefrontal Cortex. Contribution of AMPA Receptors in Hippocampo‐prefrontal Cortex Transmission

Abstract

Previous experiments in the rat have demonstrated that field CA1 and the subiculum project to the prefrontal cortex and that this direct unilateral pathway is excitatory. In the present study, anatomical and electrophysiological approaches were used to determine the transmitter mediating the excitatory responses in prefrontal cortex neurons to low-frequency stimulation of the hippocampus. The method of selective retrograde d-[3H]aspartate labelling was used to identify putative glutamatergic and/or aspartatergic hippocampal afferent fibres to the prefrontal cortex. Unilateral microinjection of d-[3H]aspartate into the prelimbic area of the prefrontal cortex resulted in the retrograde labelling of a fraction of hippocampal neurons. Some labelled cell bodies were distributed in field CA1 and the subiculum but larger numbers of neurons were detected in the ventral and intermediary subiculum. In a second series of experiments, the excitatory transmission from the hippocampus to the prefrontal cortex was pharmacologically analysed to provide further evidence for the involvement of glutamate and/or aspartate in the pathway. All prefrontal cortex neurons responding to the stimulation of the hippocampus were activated by selective agonists of the glutamate receptor subtypes alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-d-aspartate (NMDA), and these effects were selectively antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (APV) respectively. Most of the excitatory responses of prefrontal cortex neurons to single and paired-pulse stimulation of the hippocampus were antagonized by CNQX. APV only affected the excitatory response in a few cells. These results suggest that the hippocampal input to the prefrontal cortex utilizes glutamate and/or aspartate as a transmitter. Even though prefrontal cortex neurons responding to the stimulation of the hippocampus appear to have both AMPA and NMDA receptors, low-frequency stimulation of the hippocampo-prefrontal cortex pathway activates cortical neurons mostly through AMPA receptors.

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

“…However, it is possible that a bimodal S D does not exert significant control over cocaine seeking in the presence of a more salient explicit CS or a cocaine priming injection and, under these conditions, cocaine-seeking behavior does not depend on the functional integrity of the DH as shown in Experiment 2. Alternatively, cocaine-seeking behavior is perhaps controlled by the S D , but the DH mediates contextual reinstatement via its cortically projecting output region, the lateral entorhinal cortex, as opposed to the dorsal subiculum (Jay et al, 1992;Ferbinteanu and McDonald, 2001). Overall, these and the present findings suggest that the DH does not appear to mediate the incentive motivational effects of explicit cocaine-paired CSs or cocaine itself.…”

“…In contrast, the integrity of the DH is necessary for 'background' contextual fear conditioning, since post-training DH lesions abolish conditioned fear to a context that previously served as a background to CS-shock pairings and impair context-dependent latent inhibition to an explicit CS (Kim and Fanselow, 1992;Phillips and LeDoux, 1994;Maren et al, 1997;Holt and Maren, 1999). The DH interacts with subcortical brain regions via its output structure, the dorsal subiculum (Jay et al, 1992;Ferbinteanu and McDonald, 2001). Thus, it is somewhat surprising that dorsal subiculum inactivation fails to alter cocaine-seeking behavior elicited by a combination of a light-tone contextual S D and an explicit CS, or by a combination of these stimuli and a cocaine priming injection (Black et al, 2004).…”

The Prefrontal Cortex as a Key Target of the Maladaptive Response to Stress

“…Hippocampal afferents, originating in the pyramidal cells of the subiculum and ventral CA1 regions, travel through the fimbriafornix system and terminate in the mPFC, where they establish glutamatergic contacts with both pyramidal cells and interneurons (Jay et al, 1992;Jay and Witter, 1995;Tierney et al, 2004). Therefore, the occurrence and strength of LTP in the hippocampus-to-PFC pathway reflects synaptic plasticity in the PFC (Jay et al, 1992). Although it can be argued that deficits in the hippocampus-to-PFC projections may be solely the conse- quence of damage to the projecting areas, there are several reasons why this is an unlikely explanation for the present results.…”

Excitotoxic Lesions of the Rat Medial Prefrontal Cortex Effects on Abnormal Behaviors Associated with Neonatal Hippocampal Damage

“…19 , NO . 6 behaviors that implicate dysfunction of the PFC (Chambers et al 1996;Sams-Dodd et al 1997), possibly because neonatal damage of the ventral hippocampus disrupts neuronal development of the PFC, with which the hippocampus is closely interconnected (Swanson 1981;Ferino et al 1987;Jay et al 1989;Laroche et al 1990;Jay et al 1992;Carr and Sesack 1996). Because PFC dysfunction has been shown in rodents (Adler 1961;Lynch et al 1969;Iversen 1971;Pycock et al 1980;Kolb 1984;Reibaud et al 1984;Louilot et al 1989;Jaskiw et al 1991;Vezina et al 1991;Deutch 1992;Jaskiw and Weinberger 1992;King and Finlay 1995;Taber et al 1995;Karreman and Moghaddam 1996) and in primates (Kolachana et al 1995;Roberts et al 1994) to affect subcortical dopamine activity, the effect of the VH lesion on dopamine function might be indirectly mediated by an alteration at the level of the mPFC.…”