Memory Formation: The Sequence of Biochemical Events in the Hippocampus and Its Connection to Activity in Other Brain Structures
Abstract
Recent data have demonstrated a biochemical sequence of events in the rat hippocampus that is necessary for memory formation of inhibitory avoidance behavior. The sequence initially involves the activation of three different types of glutamate receptors followed by changes in second messengers and biochemical cascades led by enhanced activity of protein kinases A, C, and G and calcium-calmodulin protein kinase II, followed by changes in glutamate receptor subunits and binding properties and increased expression of constitutive and inducible transcription factors. The biochemical events are regulated early after training by hormonal and neurohumoral mechanisms related to alertness, anxiety, and stress, and 3-6 h after training by pathways related to mood and affect. The early modulation is mediated locally by GABAergic, cholinergic, and noradrenergic synapses and by putative retrograde synaptic messengers, and extrinsically by the amygdala and possibly the medial septum, which handle emotional components of memories and are direct or indirect sites of action for several hormones and neurotransmitters. The late modulation relies on dopamine D1, beta-noradrenergic, and 5HT1A receptors in the hippocampus and dopaminergic, noradrenergic, and serotoninergic pathways. Evidence indicates that hippocampal activity mediated by glutamate AMPA receptors must persist during at least 3 h after training in order for memories to be consolidated. Probably, this activity is transmitted to other areas, including the source of the dopaminergic, noradrenergic, and serotoninergic pathways, and the entorhinal and posterior parietal cortex. The entorhinal and posterior parietal cortex participate in memory consolidation minutes after the hippocampal chain of events starts, in both cases through glutamate NMDA receptor-mediated processes, and their intervention is necessary in order to complete memory consolidation. The hippocampus, amygdala, entorhinal cortex, and parietal cortex are involved in retrieval in the first few days after training; at 30 days from training only the entorhinal and parietal cortex are involved, and at 60 days only the parietal cortex is necessary for retrieval. Based on observations on other forms of hippocampal plasticity and on memory formation in the chick brain, it is suggested that the hippocampal chain of events that underlies memory formation is linked to long-term storage elsewhere through activity-dependent changes in cell connectivity.
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The amygdala appears to remain in phase 1 longer than the hippocampus, but eventually, the phase 2 (inhibitory) period develops, perhaps while the amygdala is involved in the consolidation of the emotional memory.
“The amygdala appears to remain in phase 1 longer than the hippocampus, but eventually, the phase 2 (inhibitory) period develops, perhaps while the amygdala is involved in the consolidation of the emotional memory (Izquierdo and Medina [347]; Pelletier and Paré [348]; McGaugh [88]).”
From The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes-Dodson Law (2007) · cites this paper as Izquierdo and Medina [347]
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- Authors
- Izquierdo, I., & Medina, J. H.
- Affiliations
- Universidad de Buenos Aires (AR)
- Corresponding author
- Medina, Jorge H.
- ORCID
- Medina, Jorge H.
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 1997-11
- Volume
- 68
- Issue
- 3
- Pages
- 285-316
- ISSN
- 1074-7427 (ISSN-L)
- OpenAlex
- W1965591468
- Cited by
- 959
- References
- 6
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 15 · 2023: 21 · 2022: 28 · 2021: 18 · 2020: 21 · 2019: 38 · 2018: 29 · 2017: 30 · 2016: 33 · 2015: 33 · 2014: 44 · 2013: 38 · 2012: 40
- FWCI
- 18.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- memory formation, hippocampus, passive avoidance, memory consolidation, glutamate receptors, AMPA receptors, NMDA receptor, protein kinases, calcium/calmodulin-dependent protein kinase II, transcription factors, stress hormones, amygdala, medial septum, entorhinal cortex, posterior parietal cortex, dopaminergic pathways, noradrenergic pathways, serotonin pathway, GABAergic synapses, cholinergic synapses, memory retrieval, hippocampal plasticity
- MeSH terms
- Animals, Avoidance Learning, Brain, Brain Mapping, Hippocampus, Nerve Net, Synaptic Transmission, Mental Recall, Retention, Psychology, Second Messenger Systems, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Receptors, AMPA, Neurotransmitter Agents, Rats
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