Exciting information is arising about epigenetic mechanisms and their role in long-lasting changes of neuronal gene expression that underlie important changes of neuronal and brain function. Whereas these mechanisms are active throughout life, much work points to a critical window of early postnatal development during which neuronal gene expression may be persistently “re-programmed” via epigenetic modifications. However, it remains unclear how the epigenetic machinery is modulated. Here we focus on an important example of early-life programming: the effect of sensory input from the mother on expression patterns of key stress-related genes in the developing brain. We focus on the lasting effects of this early life experience on corticotropin releasing hormone (CRH) gene expression in the hypothalamus, and describe recent work that integrates organism-wide signals and especially rhythms and patterns of maternal care, with cellular signals that in turn impact epigenetic regulation. We describe the operational brain networks that convey sensory input to CRH-expressing cells, and highlight the resulting “re-wiring” of synaptic connectivity to these neurons. We then move from intercellular to intracellular mechanisms, speculating about the induction and maintenance of lifelong CRH repression provoked by early-life experience. Elucidating such pathways is critical for understanding the enduring links between experience and gene expression. In the context of responses to stress, such mechanisms should contribute to vulnerability or resilience to stress-related disorders.

Supported By NIH Grants MH73136; P50 MH 096889 NS28912