Project 4. Molecular mechanisms of myelin deficits in a mouse model of developmental alcohol exposure

Prenatal alcohol exposure (PAE) is the most common environmental cause of neurodevelopmental brain injury, resulting in the development of fetal alcohol spectrum disorders (FASDs). Children with FASD exhibit persistent learning and behavioral disabilities, which may be due to white matter injury in the brain. The goal of our stud is to investigate how alcohol impacts the gene expression and function of oligodendrocytes, the major glial cell type that is responsible for myelinating white matter tracts in a mouse model of FASD.

Transcriptional Programs for Oligodendrocyte Differentiation​

• Investigating the transcriptional programs essential for differentiating oligodendrocyte precursors into oligodendrocytes in both gray and white matter. ​
• Utilizing powerful transgenic reporter mice, advanced transcriptomics, and touch screen learning paradigms to study myelin plasticity in cortico-thalamic neuronal circuits.​

Myelin Plasticity and Cognitive Function​

• Exploring activity-dependent, experience-mediated myelin plasticity in the adolescent brain, focusing on the mediodorsal thalamic nucleus, medial prefrontal cortex, cortico-thalamic tracts, and corpus callosum.​
• Implementing optogenetic stimulation and visuospatial cognitive learning tasks to investigate how developmental alcohol exposure impacts oligodendrocyte development and white matter plasticity.​

Molecular Mechanisms of Myelin Deficits​

• Examining the molecular mechanisms underlying myelin deficits in a mouse model of developmental alcohol exposure.​
• Investigating the role of oligodendrocyte precursor cells in differentiating into oligodendrocytes, crucial for insulating neuronal axons with the myelin sheath.​

Impact of Alcohol Exposure on Myelination​

• Studying the adaptive myelination process, which is essential for learning and memory, and how it is disrupted by alcohol exposure.​
• Addressing the vulnerability of oligodendrocyte precursor cells to alcohol exposure and the resulting decreased myelination of major white matter tracts.​
• These efforts aim to uncover novel mechanisms by which developmental alcohol exposure affects oligodendrocyte development and white matter plasticity, enhancing our understanding of functional connectivity and cognitive deficits in FASD.​