Editorial: Molecular Mechanisms for Reprogramming Hippocampal Development and Function by Early-Life Stress

The hippocampal formation is both a key component of the medial temporal lobe crucial for declarative memory and a main target of stress mediators (e.g., glucocorticoids and neuropeptides) and stress-related molecules (e.g., nutritional factors and cytokines). During the first weeks of life, the hippocampus significantly increases in volume (Zhang et al., 2005) and several critical developmental processes coincide: generation of new neurons, outgrowth of neurites, formation of synaptic contacts, and establishment of neuronal circuits (Khalaf-Nazzal and Francis, 2013). Although the neonatal hypothalamic-pituitary-adrenal (HPA) axis is relatively hyporesponsive to environmental challenges, age-appropriate stressors can activate stress response, which in turn alters hippocampal development and increases the risk to develop neuropsychiatric disorders later in life, dependent on adult life conditions, and genetic predispositions (for recent reviews, see Lucassen et al., dissecting the molecular mechanisms mediating the potentially detrimental consequences of early-life stress will provide insight into the pathophysiology and intervention of these disorders. Most studies so far focus on the mechanisms of the long-term impact of early-life stress on hippocampal plasticity in adolescence/adulthood, which are of clinical relevance. In comparison, molecular mechanisms on how stress shapes the developing hippocampus have received attention only recently (Gross et al. We therefore initiated this research topic to sum up recent findings with an emphasis on both the dynamic effects of early-life stress on hippocampal structure and function at different life stages and the immediate effects of stress on hippocampal development. Firstly, Huang provides an overview on the molecular and cellular alterations that modulate the effects of prenatal or postnatal stress on hippocampal development, and discusses how epigenetic modifications underlie the programming effects of early-life stress and contribute to the pathogenesis of epilepsy (Huang). In the dentate gyrus (DG) of the hippocampal formation, new neurons are continuously generated and selectively integrated to local circuits throughout the lifespan. Unlike the adult DG where most granule cells are mature and settled in place, during the first postnatal week the infrapyramidal blade of DG is yet to be formed and a majority of neurons are