Roles of synaptic cell adhesion molecules in the neuromodulatory systems

Synaptic cell-adhesion molecules (CAMs), also known as trans-synaptic adhesion molecules, are essential for synapse development and maintenance by physically linking presynaptic terminals to postsynaptic structures. Extensive research has established that synaptic CAMs are critical for the formation and function of various synapse types, particularly glutamatergic and GABAergic synapses. However, their roles within modulatory systems, such as dopaminergic (DA) and serotonergic (5-HT) circuits, which utilize both synaptic and non-synaptic (volume) transmission, remain poorly understood. In this mini review, we analyzed published single-cell transcriptomic datasets of DA and 5-HT neurons to characterize presynaptic CAM expression in these systems. We further summarized current knowledge regarding the contribution of presynaptic CAMs to DA and 5-HT function and discuss how postsynaptic CAM-mediated mechanisms shape dopaminergic synaptic architecture.