Funding outcome

The hippocampus is a brain region crucial for learning and memory, which are commonly affected in neurodevelopmental disorders. Our lab recently found that Cajal-Retzius (CR) neurons, a cell population important for hippocampal development, produce PD-L1, an immune-related signaling molecule that has recently been found to inhibit memory formation in adult mice. However, the role of this molecule in the developing brain remains unexplored. As the brain matures, memory becomes more precise. This increase in memory precision relies on the activity of a type of neurons called interneurons. Interestingly, when PD-L1 was deleted from CR neurons, adult mice showed improved memory, which was accompanied by increased numbers of a unique subtype of interneurons. I will test the hypothesis that CR neurons regulate the increase in memory precision during brain maturation by coordinating interneuron development via PD-L1. I will investigate the role of PD-L1 in hippocampal interneuron migration and survival (Aim 1) and function in the emergence of memory precision (Aim 2). I will do this using a combination of techniques such as genetic manipulation, immunofluorescence staining, confocal microscopy, and behavioral tests. My project will shed light on the role of PD-L1 in the transition from imprecise to precise memory during brain maturation. Understanding the contributions of this molecule to brain development might lead to repurposing PD-L1/PD-1 inhibitors, currently used in cancer therapies, to ameliorate cognitive impairments in individuals affected by neurodevelopmental disorders.