Project R-15998

Cellular and Subcellular Mapping of Glycine Receptor α2 Activity in the Adult Striatum (Research)

Due to its decline in expression after birth, the role of the Glycine α2 receptor (GlyRα2) in the adult brain has been largely overlooked. However, we recently demonstrated significant GlyRα2 expression in the adult striatum, a key structure involved in reward-motivated behavior, and discovered that it acts as a potent modulator of striatal activity. These findings position the adult striatum as a hotspot for α2 biology. Yet, crucial knowledge on its expression profile in the adult striatum, and its functional role and subcellular localization in distinct striatal cell types is missing. Therefore, this project aims to visualize the location and elucidate the function of the GlyRα2 in the adult striatum using innovative tools. Novel GlyRα2-specific antibodies and high-resolution imaging, will allow us to map its regional and cell-type-specific expression pattern in the adult striatum. Next, using a recently developed GlyRα2 conditional knockout model and electrophysiological techniques, we will determine how GlyRα2 modulates activity in specific striatal cell types and how this affects striatal output. Finally, leveraging our innovative chimeric mClYFP-GlyRα2, which combines GlyRα2 with a yellow fluorescent Cl- sensor, we will elucidate GlyRα2's subcellular localization and activity in these striatal cell types using high-resolution and super-resolution imaging. Together, this study will provide fundamental insights into GlyRα2's role as a neuromodulator in the adult striatum.

01 November 2025 - 31 October 2029