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.
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The hippocampus-mPFC pathway makes synaptic contact both with glutamatergic pyramidal neurons and GABAergic interneurons within the mPFC.
“This hippocampus-mPFC pathway makes synaptic contact both with glutamatergic pyramidal neurons and GABAergic interneurons within the mPFC”
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 Jay et al., 1992
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- Authors
- Jay, T. M., Thierry, A., Wiklund, L., & Glowinski, J.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Jay, Thérèse M.
- ORCID
- Jay, Thérèse M.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 1992-12
- Volume
- 4
- Issue
- 12
- Pages
- 1285-1295
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2100346695
- Cited by
- 187
- References
- 66
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 7 · 2022: 2 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 10 · 2012: 9
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- AMPA receptors, NMDA receptor, glutamate, aspartic acid, excitatory neurotransmission, hippocampal subiculum, prefrontal cortex, prelimbic cortex, CNQX, APV, paired-pulse stimulation, glutamatergic afferents
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