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Author Notes:

Correspondence should be directed to: drainni@emory.edu, joanna.dabrowska@rosalindfranklin.edu

The authors would also like to thank Dr. Kerry Ressler from the Department of Psychiatry, Division of Depression and Anxiety Disorders, McLean Hospital and Harvard Medical School for providing CRFp3.0CreGFP transgenic mice. We also thank Dr. Sarah Daniel for helpful comments and edits of the manuscript.


Research Funding:

This work was supported by Grant Number R00MH-096746 from the National Institute of Mental Health and start-up funds from the Chicago Medical School, Rosalind Franklin University of Medicine Science to JD, R01MH-072908 to DGR from the National Institute of Mental Health, and by the National Institutes of Health’s Office of the Director, Office of Research Infrastructure Programs, P51OD011132.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Endocrinology & Metabolism
  • Neurosciences
  • Neurosciences & Neurology
  • corticotropin-releasing factor
  • bed nucleus of the stria terminalis
  • oval nucleus
  • hypothalamus
  • raphe nucleus
  • periaqueductal grey

Targeting Corticotropin-Releasing Factor Projections from the Oval Nucleus of the Bed Nucleus of the Stria Terminalis Using Cell-Type Specific Neuronal Tracing Studies in Mouse and Rat Brain


Journal Title:

Journal of Neuroendocrinology


Volume 28, Number 12


Type of Work:

Article | Post-print: After Peer Review


The bed nucleus of the stria terminalis (BNST) is known to play a critical role in mediating the behavioural and autonomic responses to stressors. The oval nucleus of the BNST (BNSTov) contains cell bodies that synthesise the stress hormone corticotropin-releasing factor (CRF). Although afferent fibres originating from the BNSTov have been shown to innervate several key structures of the neuroendocrine and central autonomic system, the question remains as to whether some of these fibres are CRF-positive. To directly address this question, we injected a 'floxed' anterograde tracer (rAAV5/EF1a-DIO-mCherry) into the BNSTov of CRFp3.0CreGFP transgenic mice, which express a green fluorescent protein (GFP) under the control of the CRF promoter. Serial sections were then analysed for the presence of double-labelled fibres in potential projection sites. To determine whether CRF neurons in the rat BNSTov send comparable projections, we infused rat BNSTov with an adeno-associated viral vector (AAV) in which the human synapsin promoter drives enhanced GFP expression. We then used CRF immunoreactivity to examine double-labelled fluorescent fibres and axon terminals in projection sites from brain sections of the AAV-infused rats. We have observed several terminal fields in the mouse and rat brain with double-labelled fibres in the Dorsal raphe nucleus (DRD), the paraventricular nucleus of the hypothalamus and, to a lesser extent, in the ventral tegmental area. We found double-labelled terminal boutons in the nucleus accumbens shell, prelimbic cortex and posterior basolateral nucleus of the amygdala. The most intense double-labelling was found in midbrain, including substantia nigra pars compacta, red nucleus, periaqueductal grey and pontine nuclei, as well as DRD. The results of the present study indicate that CRF neurons are the output neurons of the BNSTov and they send projections not only to the centres of neuroendocrine and autonomic regulation, but also regions modulating reward and motivation, vigilance and motor function, as well as affective behaviour.

Copyright information:

© 2016 British Society for Neuroendocrinology

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