Excess of serotonin (5-HT) alters the segregation of ispilateral and contralateral retinal projections in monoamine oxidase A knock-out mice: possible role of 5-HT uptake in retinal ganglion cells during development
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Retinal ganglion cell (RGCs) project to the ipsilateral and contralateral sides of the brain in the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). Projections from both eyes are initially intermingled until postnatal day 3 (P3) but segregate into eye-specific layers by P8. We report that this segregation does not occur in monoamine oxidase A knock-out mice (MAOA-KO) that have elevated brain levels of serotonin (5-HT) and noradrenaline. The abnormal development of retinal projections can be reversed by inhibiting 5-HT synthesis from P0 to P15. We found that in MAOA-KO mice, 5-HT accumulates in a subpopulation of RGCs and axons during embryonic and early postnatal development. The RGCs do not synthesize 5-HT but reuptake the amine from the extracellular space. In both MAOA-KO and normal mice, high-affinity uptake of 5-HT and serotonin transporter (SERT) immunoreactivity are observed in retinal axons from the optic cup to retinal terminal fields in the SC and dLGN. In the dLGN, transient SERT labeling corresponds predominantly to the ipsilateral retinal projection fields. We show that, in addition to SERT, developing RGCs also transiently express the vesicular monoamine transporter gene VMAT2: thus, retinal axons could store 5-HT in synaptic vesicles and possibly use it as a borrowed neurotransmitter. Finally we show that the 5-HT-1B receptor gene is expressed by RGCs throughout the retina from E15 until adult life. Activation of this receptor is known, from previous studies, to reduce retinotectal activity; thus 5-HT in excess could inhibit activity-dependent segregation mechanisms. A hypothesis is proposed whereby, during normal development, localized SERT expression could confer specific neurotransmission properties on a subset of RGCs and could be important in the fine-tuning of retinal projections.
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Excess 5-HT produces dystrophic serotonergic neurons and migration defects in retinal projection neurons, thalamocortical axons, and cortical interneurons.
“Excess 5-HT produces dystrophic serotonergic neurons (Daubert et al., 2010) and migration defects in retinal projection neurons (Upton et al., 1999), thalamocortical axons (Vitalis et al., 2002) and cortical interneurons (Riccio et al., 2009).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Upton et al., 1999
The paper reports a defect in the postnatal segregation of retinal axon projections, not migration defects in retinal projection neurons. In “Elevated serotonin levels prevent segregation of RGC projections” (page unavailable), it says early axon topography was normal and excess 5-HT instead affected later segregation; “Number and distribution of ipsilaterally projecting RGCs” (page unavailable) reports no significant difference in the neurons’ retinal distribution. (LLM, conf=0.86)
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References 78 · Cited by 173
- Authors
- Upton, A. L., Salichon, N., Lebrand, C., Ravary, A., Blakely, R., Seif, I., & Gaspar, P.
- Affiliations
- Inserm (FR)
- Institut Curie (FR)
- Vanderbilt University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-08-15
- Volume
- 19
- Issue
- 16
- Pages
- 7007-7024
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782873
- OpenAlex
- W1604476977
- Cited by
- 173
- References
- 78
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 10 · 2016: 1 · 2015: 4 · 2014: 7 · 2013: 5 · 2012: 6
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- serotonin, retinal ganglion cells, retinal projections, dorsal lateral geniculate nucleus, superior colliculus, serotonin transporter, serotonin uptake, vesicular monoamine transporter 2, 5-HT1B receptor, norepinephrine
- MeSH terms
- Animals, Carrier Proteins, Geniculate Bodies, Functional Laterality, Membrane Glycoproteins, Mice, Inbred C3H, Mice, Inbred C57BL, Monoamine Oxidase, Nerve Tissue Proteins, Norepinephrine, Retina, Retinal Ganglion Cells, Serotonin, Superior Colliculi, Visual Pathways, Mice, Knockout, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins, Mice
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