Memory retrieval is a complex process that involves several neurotransmitter circuits, including acetylcholine, glutamate, gamma-aminobutyric acid, norepinephrine, and serotonin/5-hydroxytryptamine. Memories are stored as neurobiological traces in engram circuits of the brain, which interact with the neurotransmitter projections to facilitate retrieval. However, in patients with dementia, these circuits become less excitable due to degenerated neurotransmitter projections, making it difficult to retrieve acquired memories.
In this article, the authors suggest that artificial neuropharmacological stimulations of acquired memories with an excitation potential higher than a natural cue can excite engram circuits in the medial prefrontal cortex, which can help retrieve lost memories in dementia. They explain the neuropharmacological foundations of engram cell-mediated memory retrieval strategy in severe dementia and highlight the close interactions between periaqueductal gray, locus coeruleus, raphe nuclei, and medial prefrontal cortex and basolateral amygdala as treatment targets for memory loss.
Furthermore, the engram circuits projecting raphe nuclei, locus coeruleus, and pontomesencephalic tegmentum complex could be significant targets of memory editing and memory formation in the absence of experience, and a well-defined study of the neural events underlying the interaction of brain stem and memory will be relevant for such developments. The authors anticipate their perspective to be a starting point for more sophisticated in vivo models for neuropharmacological modulations of memory retrieval in Alzheimer’s dementia.
The article provides a comprehensive overview of memory formation and retrieval, highlighting the crucial role of neurotransmitter circuits in this process. It also proposes a new treatment strategy for memory loss in dementia and emphasizes the importance of understanding the neuropharmacological foundations of memory retrieval.
Overall, the article offers valuable insights into the complex mechanisms of memory formation and retrieval and provides a promising direction for future research in this field.
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