UCLA

Long-lasting forms of synaptic plasticity—the ability of synaptic connections to change in strength and numbers—are thought to underlie behavioral learning and memory. Long-term potentiation (LTP) is a persistent increase in synaptic strength that relies on new gene transcription and translation during an early, critical time window following LTP induction. Although many genes have been implicated in LTP through single-gene studies, a comprehensive understanding of the molecular changes necessary for LTP persistence remains missing. Furthermore, the temporal component of gene expression within this early time window remains unexplored. To address these questions, I first tested parameters that would affect detectability of differential gene expression following stimulation in mouse acute hippocampal slices. Next, I utilized a cell-type specific and cell-type inclusive whole-genome approach to profile the temporal pattern of gene expression following LTP induction and found that gene expression within excitatory neurons of CA1 neurons was bidirectional and increased over time. The changes in gene expression were enriched for regulatory features in important regulatory regions, pointing toward coordinated regulation. I also found that gene expression changes occurred in non-neuronal cell-types following LTP induction. Following these conclusions, I then laid out a conceptual framework to guide other researchers in interpreting and presenting whole-genome data. Through this work emerges a clearer perspective of gene expression during LTP and of whole-genome methodologies.