Molecular and cellular mechanisms of episodic memory formation through hippocampal synaptic plasticity
Abstract
Background: Recall of specific events, which is known as episodic memory, relies heavily on synaptic plasticity in the hippocampus. Molecular and cellular processes that mediate this phenomenon are intricate and include neuronal and glial functions, signaling pathways, and synaptic reorganization. Objective: This work will address the molecular and cellular aspects of synaptic plasticity in the hippocampus and its role in the formation of episodic memories through processes including dendritic spine remodelling, astrocytes and microglia, and epigenetics. Methodology: Literature review of recent findings and theoretical frameworks such as Morris’s neurobiological theory of the hippocampus was done to synthesize the molecular markers, signaling pathways, and neuromodulation. Experimental data regarding the involvement of calcium signaling, synaptic tagging, and protein synthesis dependent long-term potentiation (LTP) in memory formation were reviewed. Results: This paper discusses how calcium influx, CaMKII activation and CREB-mediated transcription contribute to the preservation of LTP. Dendritic spine remodeling is highlighted as a key structural process and astrocytes and microglia are identified to regulate synaptic plasticity and neural circuit function. Moreover, epigenetic mechanisms, such as histone acetylation and DNA methylation, relate synaptic activity to the expression of genes associated with memory. Conclusion: Results of this study explain the molecular and cellular mechanisms of hippocampal synaptic plasticity and the formation of episodic memory. These findings provide a basis for future research on potential treatment for memory related diseases and underscore the significance of molecular biology in cognitive neuroscience.
References
1. Martella G. Molecular Mechanisms of Synaptic Plasticity 2.0: Dynamic Changes in Neurons Functions, Physiological and Pathological Process. International Journal of Molecular Sciences. 2023; 24(16): 12685. doi: 10.3390/ijms241612685
2. Ranjan S, Dwivedi S, Singh S. Synaptic Plasticity and Its Uses. Synaptic Plasticity in Neurodegenerative Disorders; 2024.
3. Appelbaum LG, Shenasa MA, Stolz L, et al. Synaptic plasticity and mental health: methods, challenges and opportunities. Neuropsychopharmacology. 2022; 48(1): 113-120. doi: 10.1038/s41386-022-01370-w
4. de Sevilla DF, Nuñez A, Araque A, et al. Metabotropic Regulation of Synaptic Plasticity. Neuroscience. 2021; 456: 1-3. doi: 10.1016/j.neuroscience.2020.10.006
5. El Oussini H, Zhang CL, François U, et al. CA3 hippocampal synaptic plasticity supports ripple physiology during memory consolidation. Nature Communications. 2023; 14(1). doi: 10.1038/s41467-023-42969-x
6. Di Castro MA, Garofalo S, Mormino A, et al. Interleukin-15 alters hippocampal synaptic transmission and impairs episodic memory formation in mice. Brain, Behavior, and Immunity. 2024; 115: 652-666. doi: 10.1016/j.bbi.2023.11.015
7. Le AA, Lauterborn JC, Jia Y, et al. Metabotropic NMDAR Signaling Contributes to Sex Differences in Synaptic Plasticity and Episodic Memory. The Journal of Neuroscience. 2024; 44(50): e0438242024. doi: 10.1523/jneurosci.0438-24.2024
8. Le AA. Sexually Dimorphic Synaptic Plasticity: Development and Consequences for Episodic Memory [PhD thesis]. University of California, Irvine; 2023.
9. Liu H, Yang Z, Chen Y, et al. Neural oscillations and memory: unraveling the mechanisms of anesthesia-induced amnesia. Frontiers in Neuroscience. 2024; 18. doi: 10.3389/fnins.2024.1492103
10. Dong L, Zhao T, Jin Z, et al. Effect of music rhythm magnetic field on long-term potentiation of hippocampal Schaffer-CA1 synapse plasticity. Neuroscience Letters. 2024; 820: 137576. doi: 10.1016/j.neulet.2023.137576
11. Sharbafshaaer M, Cirillo G, Esposito F, et al. Harnessing Brain Plasticity: The Therapeutic Power of Repetitive Transcranial Magnetic Stimulation (rTMS) and Theta Burst Stimulation (TBS) in Neurotransmitter Modulation, Receptor Dynamics, and Neuroimaging for Neurological Innovations. Biomedicines. 2024; 12(11): 2506. doi: 10.3390/biomedicines12112506
12. Xu D. 2022. Learning in Biologically Plausible Neural Networks. In: Proceedings of the 36th Conference on Neural Information Processing Systems (NeurIPS 2022); 2022.
13. Asok A, Leroy F, Rayman JB, et al. Molecular Mechanisms of the Memory Trace. Trends in Neurosciences. 2019; 42(1): 14-22. doi: 10.1016/j.tins.2018.10.005
14. Loprinzi P, Ponce P, Frith E. Hypothesized mechanisms through which acute exercise influences episodic memory. Physiology International. 2018; 105(4): 285-297. doi: 10.1556/2060.105.2018.4.28
15. Djurisic M, Brott BK, Saw NL, et al. Activity-dependent modulation of hippocampal synaptic plasticity via PirB and endocannabinoids. Molecular Psychiatry. 2018; 24(8): 1206-1219. doi: 10.1038/s41380-018-0034-4
16. Akhondzadeh S. Hippocampal synaptic plasticity and cognition. Journal of clinical pharmacy and therapeutics. 1999; 24(4): 241-248.
17. Hollnagel JO, Cesetti T, Schneider J, et al. Lactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure. iScience. 2020; 23(7): 101316. doi: 10.1016/j.isci.2020.101316
18. Klinzing JG, Niethard N, Born J. Mechanisms of systems memory consolidation during sleep. Nature Neuroscience. 2019; 22(10): 1598-1610. doi: 10.1038/s41593-019-0467-3
19. Sateesh S, Abraham WC. Neurophysiological and molecular approaches to understanding the mechanisms of learning and memory. Journal of the Royal Society of New Zealand. 2020; 51(1): 4-23. doi: 10.1080/03036758.2020.1796719
20. Gershman SJ. The molecular memory code and synaptic plasticity: A synthesis. Biosystems. 2023; 224: 104825. doi: 10.1016/j.biosystems.2022.104825
Copyright (c) 2025 Author(s)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright on all articles published in this journal is retained by the author(s), while the author(s) grant the publisher as the original publisher to publish the article.
Articles published in this journal are licensed under a Creative Commons Attribution 4.0 International, which means they can be shared, adapted and distributed provided that the original published version is cited.
Submit a Paper
