Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans.

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_2CR) in regulating memory. Transgenic mice expressing a humanized HTR2C 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_2CRs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT_2CR agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse mo

SUBMITTER: Liu H 

PROVIDER: S-EPMC11212768 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature