Serotonin Strengthens a Developing Glutamatergic Synapse through a PI3K-Dependent Mechanism.

It is well established that, during neural circuit development, glutamatergic synapses become strengthened via NMDA receptor (NMDAR)-dependent upregulation of AMPA receptor (AMPAR)-mediated currents. In addition, however, it is known that the neuromodulator serotonin is present throughout most regions of the vertebrate brain while synapses are forming and being shaped by activity-dependent processes. This suggests that serotonin may modulate or contribute to these processes. Here, we investigate the role of serotonin in the developing retinotectal projection of the Xenopus tadpole. We altered endogenous serotonin transmission in stage 48/49 (∼10-21 days postfertilization) Xenopus tadpoles and then carried out a set of whole-cell electrophysiological recordings from tectal neurons to assess retinotectal synaptic transmission. Because tadpole sex is indeterminate at these early stages of development, experimental groups were composed of randomly chosen tadpoles. We found that pharmacologically enhancing and reducing serotonin transmission for 24 h up- and downregulates, respectively, AMPAR-mediated currents at individual retinotectal synapses. Inhibiting 5-HT2 receptors also significantly weakened AMPAR-mediated currents and abolished the synapse strengthening effect seen with enhanced serotonin transmission, indicating a 5-HT2 receptor-dependent effect. We also determine that the serotonin-dependent upregulation of synaptic AMPAR currents was mediated via an NMDAR-independent, PI3K-dependent mechanism. Altogether, these findings indicate that serotonin regulates AMPAR currents at developing synapses independent of NMDA transmission, which may explain its role as an enabler of activity-dependent plasticity.

A circadian-dependent preference for light displayed by Xenopus tadpoles is modulated by serotonin.

Innate visually guided behaviors are thought to promote survival by guiding organisms to sources of food and safety and away from harm without requiring learning. Historically, innate behaviors have been considered hard-wired and invariable, but emerging evidence shows that many innate behaviors are flexible and complex due to modulation. Here, we investigate the modulation of the innate preference for light displayed by the Xenopus laevis tadpole, an exceptionally invasive and well-studied organism that is known to display several different innate visually guided behaviors. We found that tadpoles display a circadian-regulated oscillation in their preference for light over dark which can be altered by experimentally increasing or decreasing levels of serotonin transmission. We also found that endogenous levels of serotonin transmission during the day maintain a consistently moderate preference for light. Theoretically, a moderate preference for light, as opposed to a strong preference, optimizes survival by rendering tadpoles' behavior less predictable.