Understanding SynGAP1 regulatory mechanisms using an optical reporter of ERK activity

  • Awarded: 2018
  • Award Type: Bridge to Independence
  • Award #: 479737

A growing number of autism spectrum disorder (ASD) risk genes are found to play a role in synaptic plasticity. A subset of these genes are key regulators of intracellular signaling cascades with both the ERK pathway and its negative regulator, SynGAP1, being strongly implicated in ASD. However, the basic mechanisms by which SynGAP1 regulates ERK signaling and synaptic plasticity in the intact mammalian brain remains poorly understood, mainly due to technical difficulties associated with monitoring ERK and neuronal activity in the intact brain. This gap in our knowledge makes it difficult to understand how alterations in ERK/SynGAP1 signaling lead to an increase in ASD risk.

In order to elucidate the mechanisms by which SynGAP1 regulates ERK signaling, Sung Eun “Samuel” Kwon will use a recently developed optical reporter for ERK activity1, combined with a neuronal activity reporter, to monitor the dynamics of ERK signaling and neuronal activity in awake-behaving SynGAP heterozygous mutant mice. This will allow Kwon to test whether SynGAP deficiency leads to abnormalities in ERK signaling and neural plasticity in vivo. Kwon plans to combine this approach with intersectional genetic tools and mouse behavior to further identify specific cell types and circuits affected by SynGAP deficiency.


1.Regot S. et al. Cell 157, 1724-1734 (2014) PubMed
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