Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38941473.
- Also identified by DOI 10.1126/sciadv.adl2675 and PMC identifier 11212768.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Declined memory is a hallmark of Alzheimer's disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of 5-HT 2C receptor (5-HT<sub>2C</sub>R) in regulating memory. Transgenic mice expressing a humanized <i>HTR2C</i> mutation exhibit impaired plasticity of hippocampal ventral CA1 (vCA1) neurons and reduced memory. Further, 5-HT neurons project to and synapse onto vCA1 neurons. Disruption of 5-HT synthesis in vCA1-projecting neurons or deletion of 5-HT<sub>2C</sub>Rs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT<sub>2C</sub>R agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HT<sub>2C</sub>R signaling regulates memory, which may inform the use of 5-HT<sub>2C</sub>R agonists in the treatment of dementia.
Medical subject headings
- Receptor, Serotonin, 5-HT2C
- Memory
- Mice, Transgenic
- Neuronal Plasticity
- Alzheimer Disease