{Reference Type}: Journal Article
{Title}: Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans.
{Author}: Liu H;He Y;Liu H;Brouwers B;Yin N;Lawler K;Keogh JM;Henning E;Lee DK;Yu M;Tu L;Zhang N;Conde KM;Han J;Yan Z;Scarcelli NA;Liao L;Xu J;Tong Q;Zheng H;Sun Z;Yang Y;Wang C;He Y;Farooqi IS;Xu Y;
{Journal}: Sci Adv
{Volume}: 10
{Issue}: 26
{Year}: 2024 Jun 28
{Factor}: 14.957
{DOI}: 10.1126/sciadv.adl2675
{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-HT2CR) 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-HT2CRs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT2CR agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HT2CR signaling regulates memory, which may inform the use of 5-HT2CR agonists in the treatment of dementia.