Hypothalamic effector neurons and extended circuitries activated in "neurogenic" stress: a comparison of footshock effects exerted acutely, chronically, and in animals with controlled glucocorticoid levels

J Comp Neurol. 1998 Apr 6;393(2):244-66.


Immunolocalization of Fos protein was used to identify and characterize hypothalamic visceromotor populations responsive to acute and chronic intermittent footshock stress, and candidate afferent mediators of hypothalamic effects. Exposure to a single 30 minute footshock session induced maximal Fos expression in the paraventricular hypothalamic nucleus (PVH) 2 hours after the challenge; activated cells corresponded principally to hypophysiotropic neurons expressing corticotropin-releasing factor, with secondary involvement of magnocellular oxytocinergic and autonomic-related projection neurons. Extrahypothalamic cell groups activated in response to acute footshock included ones associated with the processing or modulation of somatosensory/nociceptive inputs, the limbic region of the telencephalon, and visceral sensory mechanisms. Rats with constant corticosterone levels displayed enhanced footshock-induced Fos expression in the parvicellular compartment of the PVH, as well as in certain limbic and somatosensory cell groups, the locus coeruleus, but not in medullary catecholaminergic cell groups. Animals subjected to chronic intermittent stress (2 sessions/day for 7 days) showed only modest evidence of habituation of cellular activation responses in the PVH and most extrahypothalamic regions. Rats bearing retrograde tracer deposits in the PVH and killed 2 hours after acute footshock displayed Fos-positive retrogradely labeled neurons principally in medullary catecholaminergic cell groups, with secondary foci in the hypothalamus, limbic region, and pontine tegmentum. This characterization of footshock-responsive systems identifies cell groups that are in a position to (1) mediate acute stress effects on hypothalamic visceromotor neurons, (2) comprise targets for corticosteroid negative feedback effects, and/or (3) underlie habituation of the neuroendocrine limb of the stress response.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autonomic Nervous System / cytology
  • Catecholamines / metabolism
  • Corticosterone / metabolism*
  • Corticosterone / pharmacology
  • Corticotropin-Releasing Hormone / metabolism
  • Electroshock
  • Glucocorticoids / metabolism*
  • Hypothalamo-Hypophyseal System / cytology
  • Limbic System / cytology
  • Male
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Neurosecretory Systems / cytology
  • Paraventricular Hypothalamic Nucleus / cytology*
  • Pituitary-Adrenal System / cytology
  • Prosencephalon / cytology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Somatosensory Cortex / cytology
  • Stress, Physiological / physiopathology*
  • Time Factors


  • Catecholamines
  • Glucocorticoids
  • Proto-Oncogene Proteins c-fos
  • Corticotropin-Releasing Hormone
  • Corticosterone