Decoding experience-dependent transcription in the regulation of neural circuit and behavioral plasticity

Animal brains are wired according to genetic programs that evolved
over millions of years. Much of our behavior, however, is shaped by
experiences during life that reprogram the brain by altering gene
expression. Here we aim to deliver a much-needed understanding of
how these lasting changes alter brain function. Many genes
regulated by experience have been identified. Yet, how they sculpt
neural circuits and behavior is poorly understood. To bridge this gap,
we will use the mini-brain of C. elegans and its homeostatic circuit for
gas sensing. We recently discovered that activity-dependent gene
expression in this circuit modulates behavioral responses to sensory
input. We will use recently developed tools to identify which genes
are regulated by different experiences in the gas-sensing neurons.
Pilot data suggests these include several genes conserved between
C. elegans and humans. We will study how these genes contribute to
experience-dependent changes in neural activity and behavior, and
unravel the cellular pathways regulating their expression. This project
will shed light on fundamental mechanisms that underpin experiencedependent
gene expression and its role in neural plasticity. Because
the molecular pathways and gene targets involved in activityregulated
transcription are evolutionarily ancient and well conserved,
from worms to humans, we expect our findings will contribute to
insights on how experience reprograms more complex brains.