Title: Effect of thyroid hormone on cortical neuron maturation and activity
Directors: Frédéric FLAMANT and WONG Jieming
Discipline: Biology
Status: Ongoing Project
Starting date: 2022
Directors
Summary
The aim of the project is to clarify the influence of thyroid hormone receptors, which are nuclear receptors encoded by the Thra and Thrb genes, on the maturation and function of a specific type of neurons within the cortex: the GABAergic neurons. For this purpose we will also address the influence of thyroid hormone on gene expression. We will also perform an in vivo analyses of gene expression in GABAergic neurons extracted from the cortex of mice expressing a Thra mutation, or specifically in fast-spiking interneurons. We will then focus on the analysis on genes that encode components of the extracellular matrix. More specifically, fast-spiking interneurons elaborate a highly glycosylated extracellular matrix called the perineuronal net. The perineuronal net is known to exert an important influence on synaptic plasticity. Our working hypothesis is that thyroid hormone is required for the synthesis of the perineuronal net, and that the cognitive alterations observed in patients with thyroid hormone deficiency are due to a defect in this process. Immunohistochemistry, protein biochemistry and electrophysiology will be used to complete the gene expression analysis and gain a global view on the influence of thyroid hormone on the maturation of the cortical neuronal network.