Developmental Profile of Glutamatergic Synapses in Fragile X

FRAXA Research Foundation has awarded a $90,000 research fellowship to Dr. Tue Banke. With this award, Dr. Banke is investigating how glutamate receptors at neuronal synapses – essential building blocks of learning and memory – are impacted in Fragile X syndrome. Dr. Banke recently left Aarhus University in Denmark to continue his research first as a visiting scholar and now as an assistant professor at the University of Washington.

$90,000 Grant

Tue Banke, PhD
FRAXA Investigator

University of Washington
2019 FRAXA Research Grant
$90,000 over 2 Years

by Tue Banke, PhD

The formation of neuron-neuron connections (synapses) in the brain is known to be altered in both Fragile X syndrome (FXS) animals and patients, and as such is thought to be an important intervention point for a potential cure of the disorder. In FXS the altered synapse formations have often been characterized as “enhanced spine density” (higher number of spines/synapses) and altered neurophysiological properties like neurotransmission and/or synaptic plasticity. These processes are necessary for proper brain [circuitry] development.

Glutamate receptors are an important synaptic “building block” directly involved in forming synapses, shaping synaptic responses, and modifying the strength of synaptic connections. We have previously found that altering glutamate receptor function strongly impacts synapse properties: lack of synaptic potentiation observed in FXS animals can be fully restored by antagonizing (blocking) the glutamate receptor subunit GluN2A (ref). Furthermore, the expression level of GluN2 subunits controls the growth of new synapses, altering spine density (ref). These data suggest that changes in glutamate receptor expression – or its trafficking – can lead to altered synaptic and spine properties. These changes could explain the brain function deficits observed in FXS.

In this project, we will investigate in detail how loss of FMRP affects the expression of synaptic glutamate receptors and other synaptic proteins, and how their altered expression affects synaptic properties. Understanding the developmental profile of glutamate receptors and other key synaptic proteins is crucial for our understanding of Fragile X syndrome.

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