Neuroplasticity of the Hypothalamic–Pituitary–Adrenal Axis Early in Life Requires Recurrent Recruitment of Stress-Regulating Brain Regions

In PVT (unlike ACe and BnST), major Fos activation requires recurrent handling. The number of Fos-labeled cells in PVT, ACe, and BnST were compared in pups handled daily during P2–P9 (and perfused 30 min after their return to the dam on P9), handled once on P9 (and perfused at the same time point), deprived of maternal care for 3 h on P9 (and not returned to the home cage; a “negative control” for maternal sensory input), or remaining undisturbed during P2–P9. The number of Fos-positive cells in PVT of pups handled once (bar with diagonal lines) was not different from that in undisturbed pups (black bar), whereas recurrent handling (white bar) caused a threefold increase in Fos-labeled cells (F_(3,16) = 20.87; p < 0.01). In ACe and BnST, single and recurrent handling induced Fos expression to similar extents. ACe, n = 2–3 brains per time point; BnST, n = 2–3 brains per time point; PVT, n = 3–4 brains per time point. * indicates that values differ statistically from maternally deprived and undisturbed control groups; ** indicates that values are significantly different from all other groups; p < 0.05.