Neuroplasticity of the hypothalamic-pituitary-adrenal axis early in life requires recurrent recruitment of stress-regulating brain regions

Kristina A. Simeone, Yuncai Chen, Tallie Z. Baram

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

An eloquent example of experience-induced neuroplasticity involves the enduring effects of daily "handling" of rat pups on the expression of genes regulating hormonal and behavioral responses to stress. Handling-evoked augmentation of maternal care of pups induces long-lasting reduction of hypothalamic corticotropin releasing hormone (CRH) expression and upregulates hippocampal glucocorticoid receptor levels. These changes promote a lifelong attenuation of hormonal stress responses. We have found previously that handling-evoked downregulation of CRH expression occurs already by postnatal day 9, implicating it as an early step in this experience-induced neuroplasticity. Here, we investigated the neuronal pathways and cellular mechanisms involved. CRH mRNA expression in hypothalamic paraventricular nucleus (PVN) diminished after daily handling but not after handling once only, indicating that "recurrent" handling was required for this effect. Return of handled pups to their cage provoked a burst of nurturing behavior in dams that, in turn, induced transient, coordinate Fos expression in selected regions of the pups' brains. These included central nucleus of the amygdala (ACe) and bed nucleus of the stria terminals (BnST), regions that are afferent to PVN and influence CRH expression there. Whereas handling once sufficed to evoke Fos expression within ACe and BnST, expression in thalamic paraventricular nucleus, a region involved in storing and processing stress-related experience, required recurrent handling. Fos induction in all three regions elicited reduced transcription factor phosphorylation, followed by attenuated activation of CRH gene transcription within the PVN. These studies provide a neurobiological foundation for the profound neuroplasticity of stress-related genes evoked by early-life experience.

Original languageEnglish
Pages (from-to)2434-2442
Number of pages9
JournalJournal of Neuroscience
Volume26
Issue number9
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

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Neuronal Plasticity
Corticotropin-Releasing Hormone
Brain
Paraventricular Hypothalamic Nucleus
Midline Thalamic Nuclei
Pituitary Hormone-Releasing Hormones
Handling (Psychology)
Glucocorticoid Receptors
Genes
Transcription Factors
Up-Regulation
Down-Regulation
Phosphorylation
Mothers
Gene Expression
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Neuroplasticity of the hypothalamic-pituitary-adrenal axis early in life requires recurrent recruitment of stress-regulating brain regions. / Simeone, Kristina A.; Chen, Yuncai; Baram, Tallie Z.

In: Journal of Neuroscience, Vol. 26, No. 9, 01.03.2006, p. 2434-2442.

Research output: Contribution to journalArticle

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