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

Delphine Gobert1, Anne Schohl1, Elena Kutsarova1

  • 1Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada.

Developmental Neurobiology
|September 30, 2020
PubMed
Summary
This summary is machine-generated.

Target of Rapamycin Complex 1 (TORC1) signaling regulates dendritic growth and excitatory synapse maturation. Over-activation of TORC1 creates an excitatory-inhibitory imbalance, impacting neural circuit development and potentially autism spectrum disorder (ASD).

Keywords:
Xenopus laevisdevelopmentelectroporationmTORreceptive fieldretinotectal

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Newly synthesized proteins are crucial for neural circuit development.
  • Dysregulated protein translation is implicated in autism spectrum disorder (ASD).
  • The Target of Rapamycin Complex 1 (TORC1) pathway is a key regulator of cell growth and protein synthesis.

Purpose of the Study:

  • To investigate the role of TORC1 signaling in synaptic and dendritic development.
  • To determine how TORC1 affects excitatory and inhibitory synapse balance.
  • To understand TORC1's influence on neural circuit integration in vivo.

Main Methods:

  • Utilized the Xenopus laevis retinotectal system for in vivo studies.
  • Employed Rheb overexpression to acutely activate TORC1 signaling.
  • Assessed dendritic growth, branching, and synaptic maturation (excitatory and inhibitory).

Main Results:

  • TORC1 signaling was found to regulate dendritic growth and branching.
  • TORC1 over-activation enhanced excitatory synapse maturation by recruiting AMPA receptors.
  • TORC1 over-activation led to an imbalance in the excitatory-to-inhibitory ratio without affecting inhibitory transmission.
  • Rheb overexpression enlarged excitatory visual input fields, suggesting altered retinotopic refinement.

Conclusions:

  • Acute, local manipulation of TORC1 selectively regulates excitatory synapse number and maturity.
  • TORC1 plays a critical role in balancing excitatory and inhibitory synaptic transmission during brain development.
  • Findings highlight TORC1's specific role in excitatory synapse regulation, contrasting with broader effects seen in other studies.