Characterization of corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus of Crh-IRES-Cre mutant mice

PLoS One. 2013 May 28;8(5):e64943. doi: 10.1371/journal.pone.0064943. Print 2013.


Corticotropin-releasing hormone (CRH)-containing neurons in the paraventricular nucleus of the hypothalamus (PVN) initiate and control neuroendocrine responses to psychogenic and physical stress. Investigations into the physiology of CRH neurons, however, have been hampered by the lack of tools for adequately targeting or visualizing this cell population. Here we characterize CRH neurons in the PVN of mice that express tdTomato fluorophore, generated by crosses of recently developed Crh-IRES-Cre driver and Ai14 Cre-reporter mouse strains. tdTomato containing PVN neurons in Crh-IRES-Cre;Ai14 mice are readily visualized without secondary-detection methods. These neurons are predominantly neuroendocrine and abundantly express CRH protein, but not other PVN phenotypic neuropeptides. After an acute stress, a large majority of tdTomato cells express neuronal activation marker c-Fos. Finally, tdTomato PVN neurons exhibit homogenous intrinsic biophysical and synaptic properties, and can be optogenetically manipulated by viral Cre-driven expression of channelrhodopsin. These observations highlight basic cell-type characteristics of CRH neurons in a mutant mouse, providing validation for its future use in probing neurophysiology of endocrine stress responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Corticotropin-Releasing Hormone / metabolism*
  • Glutamic Acid / metabolism
  • Integrases / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neurons / metabolism*
  • Neurons / physiology
  • Optogenetics
  • Paraventricular Hypothalamic Nucleus / cytology*
  • Paraventricular Hypothalamic Nucleus / physiology
  • Phenotype
  • Ribosomes / metabolism*
  • Stress, Physiological
  • Synaptic Transmission
  • gamma-Aminobutyric Acid / metabolism


  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Corticotropin-Releasing Hormone
  • Cre recombinase
  • Integrases