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It is well established that, during neural circuit development, glutamatergic synapses become strengthened via NMDA receptor (NMDAR)-dependent up-regulation 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 (approximately 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 comprised of randomly chosen tadpoles. We found that pharmacologically enhancing and reducing serotonin transmission for 24 hours up- and down-regulates, respectively, AMPAR-mediated currents at individual retinotectal synapses. Inhibiting 5HT-2 receptors also significantly weakened AMPAR-mediated currents and abolished the synapse strengthening effect seen with enhanced serotonin transmission, indicating a 5HT-2 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 synapse independent of NMDA transmission, which may explain its role as an enabler of activity-dependent plasticity.Significance Statement Glutamate is the main excitatory transmitter in the central nervous system, and so the formation of synapses to support robust glutamatergic transmission is important for healthy brain function. It is well established that, during development, activity-dependent, Hebbian-like plasticity strengthens and refines glutamatergic synapses. Here, we report that the neuromodulator serotonin also strengthens developing glutamatergic synapses. This strengthening occurs through an activity independent mechanism that involves the activation of phosphoinositide signaling. Overall, this study suggests that a combination of activity dependent and independent mechanisms strengthens glutamatergic synapses during development.
Akerman,
Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo.
2006, Pubmed,
Xenbase
Akerman,
Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo.
2006,
Pubmed
,
Xenbase
Arendt,
PIP3 controls synaptic function by maintaining AMPA receptor clustering at the postsynaptic membrane.
2010,
Pubmed
Baroncelli,
Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex.
2010,
Pubmed
Bastos,
Fluoxetine-induced plasticity in the rodent visual system.
1999,
Pubmed
Belmer,
Mapping the connectivity of serotonin transporter immunoreactive axons to excitatory and inhibitory neurochemical synapses in the mouse limbic brain.
2017,
Pubmed
Bowe,
Developmental increase in the sensitivity to magnesium of NMDA receptors on CA1 hippocampal pyramidal cells.
1990,
Pubmed
Bruno,
A circadian-dependent preference for light displayed by Xenopus tadpoles is modulated by serotonin.
2022,
Pubmed
,
Xenbase
Butt,
Sculpting the visual map: the distribution and function of serotonin-1A and serotonin-1B receptors in the optic tectum of the frog.
2002,
Pubmed
Cheng,
Activation and inhibition of tph2 serotonergic neurons operate in tandem to influence larval zebrafish preference for light over darkness.
2016,
Pubmed
Conn,
Selective 5HT-2 antagonists inhibit serotonin stimulated phosphatidylinositol metabolism in cerebral cortex.
1984,
Pubmed
De Lucchini,
Expression of 5-HT2B and 5-HT2C receptor genes is associated with proliferative regions of Xenopus developing brain and eye.
2003,
Pubmed
,
Xenbase
Deeg,
Sensory modality-specific homeostatic plasticity in the developing optic tectum.
2011,
Pubmed
,
Xenbase
Dong,
Visual avoidance in Xenopus tadpoles is correlated with the maturation of visual responses in the optic tectum.
2009,
Pubmed
,
Xenbase
Durand,
Long-term potentiation and functional synapse induction in developing hippocampus.
1996,
Pubmed
González,
Neonatal tryptophan dietary restriction alters development of retinotectal projections in rats.
2008,
Pubmed
Gu,
Involvement of serotonin in developmental plasticity of kitten visual cortex.
1995,
Pubmed
Hamodi,
Region-specific regulation of voltage-gated intrinsic currents in the developing optic tectum of the Xenopus tadpole.
2014,
Pubmed
,
Xenbase
Hunt,
An Innate Color Preference Displayed by Xenopus Tadpoles Is Persistent and Requires the Tegmentum.
2020,
Pubmed
,
Xenbase
Kirkwood,
Serotonergic control of developmental plasticity.
2000,
Pubmed
Kojic,
Columnar distribution of serotonin-dependent plasticity within kitten striate cortex.
2000,
Pubmed
Korn,
Quantal analysis and synaptic efficacy in the CNS.
1991,
Pubmed
Lauder,
Serotonin as a differentiation signal in early neurogenesis.
1978,
Pubmed
Leinekugel,
Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus.
1997,
Pubmed
Liao,
Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice.
1995,
Pubmed
Liu,
Serotonin-induced growth of pulmonary artery smooth muscle requires activation of phosphatidylinositol 3-kinase/serine-threonine protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase 1.
2006,
Pubmed
Liu,
Presenilin Regulates Retinotectal Synapse Formation through EphB2 Receptor Processing.
2018,
Pubmed
,
Xenbase
Maya Vetencourt,
The antidepressant fluoxetine restores plasticity in the adult visual cortex.
2008,
Pubmed
McCorvy,
Structure and function of serotonin G protein-coupled receptors.
2015,
Pubmed
Nguyen,
Neurotransmitters as early signals for central nervous system development.
2001,
Pubmed
Niswender,
Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin.
2003,
Pubmed
Penedo,
Nutritional tryptophan restriction impairs plasticity of retinotectal axons during the critical period.
2009,
Pubmed
Pratt,
Homeostatic regulation of intrinsic excitability and synaptic transmission in a developing visual circuit.
2007,
Pubmed
,
Xenbase
Pratt,
An Evolutionarily Conserved Mechanism for Activity-Dependent Visual Circuit Development.
2016,
Pubmed
Shihan,
A simple method for quantitating confocal fluorescent images.
2021,
Pubmed
Shutoh,
Long term depletion of serotonin leads to selective changes in glutamate receptor subunits.
2000,
Pubmed
Sodhi,
Serotonin and brain development.
2004,
Pubmed
Vanhaesebroeck,
Synthesis and function of 3-phosphorylated inositol lipids.
2001,
Pubmed
Wang,
Blockade of serotonin-2C receptors by mesulergine reduces ocular dominance plasticity in kitten visual cortex.
1997,
Pubmed
Wu,
Maturation of a central glutamatergic synapse.
1996,
Pubmed
,
Xenbase
Xu,
Structure and plasticity of silent synapses in developing hippocampal neurons visualized by super-resolution imaging.
2020,
Pubmed
Xu-Friedman,
Probing fundamental aspects of synaptic transmission with strontium.
2000,
Pubmed
