TORC1 selectively regulates synaptic maturation and input convergence in the developing visual system
| Autor: | Elena Kutsarova, Anne Schohl, Edward S. Ruthazer, Delphine Gobert |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Superior Colliculi Xenopus TORC1 signaling AMPA receptor Mechanistic Target of Rapamycin Complex 1 Biology Inhibitory postsynaptic potential Xenopus laevis 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Developmental Neuroscience Biological neural network Animals Humans Visual Pathways biology.organism_classification Microscopy Fluorescence Multiphoton 030104 developmental biology Receptive field Synapses Excitatory postsynaptic potential biology.protein Neuroscience 030217 neurology & neurosurgery RHEB |
| Zdroj: | Developmental Neurobiology. 80:332-350 |
| ISSN: | 1932-846X 1932-8451 |
| DOI: | 10.1002/dneu.22782 |
| Popis: | Newly synthesized proteins support the development of functional neural circuits and previous work has suggested that dysregulated translation mediates certain forms of autism spectrum disorder (ASD). Here, we investigated the role of Target of Rapamycin Complex 1 (TORC1) in synaptic and dendritic development in vivo in the retinotectal system of Xenopus laevis tadpoles. We found that TORC1 signaling regulates dendritic growth and branching and that acute over-activation of TORC1 by Rheb overexpression drove enhanced maturation of excitatory synapses by recruiting AMPA receptors. Interestingly, TORC1 over-activation did not affect inhibitory transmission, resulting in a significant imbalance in the excitatory-to-inhibitory ratio. Rheb overexpression also enlarged excitatory visual input fields in tectal neurons, consistent with dysregulation of retinotopic input refinement and integration of the cell into the circuit. In contrast to other reports that mainly found impairments in synaptic inhibition using broad systemic deletion or mutation of TORC1 regulatory proteins, our findings from acute, local manipulation of TORC1 reveal its critical role in selectively regulating the number and maturity of excitatory, but not inhibitory, synapses in the developing brain. |
| Databáze: | OpenAIRE |
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