TORC1 selectively regulates synaptic maturation and input convergence in the developing visual system

• Published in: Developmental neurobiology (Hoboken, N.J.) Vol. 80; no. 9-10; pp. 332 - 350
• Main Authors: Gobert, Delphine, Schohl, Anne, Kutsarova, Elena, Ruthazer, Edward S.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2020
• Subjects: Autism; Dendritic branching; development; electroporation; Functional morphology; Gene deletion; Maturation; mTOR; Neural networks; Rapamycin; receptive field; Regulatory proteins; Retina; retinotectal; Superior colliculus; Synaptogenesis; TOR protein; Visual pathways; Visual system; Xenopus laevis; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; mTOR; receptive field; development; retinotectal; electroporation; Xenopus laevis
• ISSN: 1932-8451; 1932-846X
• DOI: 10.1002/dneu.22782

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.