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ABSTRACT The retinotectal projection, the direct synapse between retinal ganglion cells (RGCs) of the eye and tectal neurons of the optic tectum, is a major component of the amphibian visual system. A model of circuit formation, this projection has been studied in detail. There are, however, other retinorecipient targets that also comprise the amphibian visual system such as the pretectum and ventral midbrain tegmentum. Understanding how these other components of the visual system form and function will lead to a more comprehensive understanding of how the visual system, as a whole, assembles and functions. Toward this aim, here we describe the functional development of theXenopustadpole accessory optic system (AOS), a direct synaptic connection between RGC axons and the basal optic nucleus of the midbrain tegmentum. The AOS is highly conserved across vertebrates. It functions as the sensory side of the optokinetic and optomotor reflexes, compensatory eye and body movements, respectively, that stabilize the visual scene as the organism moves through it. Using an isolated brain preparation and whole‐cell electrophysiological approaches, we compared the development of the AOS and retinotectal projection. We found that these two retinofugal projections display distinct developmental programs, which appear to mirror their different functions. Retinotectal synapses moved through a dynamic phase of previously described NMDA receptor‐dependent refinement, a process that is known to sharpen the retinotopic map and thereby visual acuity. In contrast, the AOS synapse appeared more stable and activity independent across development, indicative of a hardwired circuit, built to support reflexive optic behaviors. 

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 theXenopustadpole. We altered endogenous serotonin transmission in stage 48/49 (∼10–21 days postfertilization)Xenopustadpoles 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-HT₂receptors also significantly weakened AMPAR-mediated currents and abolished the synapse strengthening effect seen with enhanced serotonin transmission, indicating a 5-HT₂receptor–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.