Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-releasing Hormone on the Acoustic Startle Reflex

Overview

Journal J Neurosci

Specialty Neurology

Date 1997 Aug 15

PMID 9236251

Citations 179

Authors

Y Lee

M Davis

Affiliations

Soon will be listed here.

Abstract

Previously, we demonstrated that transection of the fimbria/fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRH-enhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses.

Citing Articles

The lateralized LC-NAergic system distinguishes vicarious versus direct fear in mice.

Kim J, Choi D, Shin H Nat Commun. 2025; 16(1):2364.

PMID: 40064917 PMC: 11894102. DOI: 10.1038/s41467-025-57701-0.

Abnormal cytoskeletal remodeling but normal neuronal excitability in a mouse model of the recurrent developmental and epileptic encephalopathy-susceptibility KCNB1-p.R312H variant.

Bortolami A, Forzisi Kathera-Ibarra E, Balatsky A, Dubey M, Amin R, Venkateswaran S Commun Biol. 2024; 7(1):1713.

PMID: 39738805 PMC: 11685548. DOI: 10.1038/s42003-024-07344-6.

Beyond awareness: the binding of reflexive mechanisms with the conscious mind: a perspective from default space theory.

Jerath R, Beveridge C Front Hum Neurosci. 2024; 18:1520138.

PMID: 39726692 PMC: 11670070. DOI: 10.3389/fnhum.2024.1520138.

Effects of early maternal care on anxiety and threat learning in adolescent nonhuman primates.

Morin E, Siebert E, Howell B, Higgins M, Jovanovic T, Kazama A Dev Cogn Neurosci. 2024; 71():101480.

PMID: 39642805 PMC: 11665541. DOI: 10.1016/j.dcn.2024.101480.

Acute stress yields a sex-dependent facilitation of signaled active avoidance in rats.

Plas S, Oleksiak C, Pitre C, Melton C, Moscarello J, Maren S Neurobiol Stress. 2024; 31:100656.

PMID: 38994219 PMC: 11238190. DOI: 10.1016/j.ynstr.2024.100656.

References

Merlo Pich E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob G . Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J Neurosci. 1995; 15(8):5439-47. PMC: 6577636. View

Arnold F, De Lucas Bueno M, Shiers H, Hancock D, Evan G, Herbert J . Expression of c-fos in regions of the basal limbic forebrain following intracerebroventricular corticotropin-releasing factor in unstressed or stressed male rats. Neuroscience. 1992; 51(2):377-90. DOI: 10.1016/0306-4522(92)90322-s. View

Helmstetter F, Bellgowan P . Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. Behav Neurosci. 1994; 108(5):1005-9. DOI: 10.1037//0735-7044.108.5.1005. View

Sun N, Roberts L, Cassell M . Rat central amygdaloid nucleus projections to the bed nucleus of the stria terminalis. Brain Res Bull. 1991; 27(5):651-62. DOI: 10.1016/0361-9230(91)90041-h. View

Holstege G, Meiners L, Tan K . Projections of the bed nucleus of the stria terminalis to the mesencephalon, pons, and medulla oblongata in the cat. Exp Brain Res. 1985; 58(2):379-91. DOI: 10.1007/BF00235319. View

Dunn A, Berridge C . Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses?. Brain Res Brain Res Rev. 1990; 15(2):71-100. DOI: 10.1016/0165-0173(90)90012-d. View

Honkaniemi J . Colocalization of peptide- and tyrosine hydroxylase-like immunoreactivities with Fos-immunoreactive neurons in rat central amygdaloid nucleus after immobilization stress. Brain Res. 1992; 598(1-2):107-13. DOI: 10.1016/0006-8993(92)90173-7. View

Rassnick S, Heinrichs S, Britton K, Koob G . Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. Brain Res. 1993; 605(1):25-32. DOI: 10.1016/0006-8993(93)91352-s. View

Cummings S, Elde R, ELLS J, LINDALL A . Corticotropin-releasing factor immunoreactivity is widely distributed within the central nervous system of the rat: an immunohistochemical study. J Neurosci. 1983; 3(7):1355-68. PMC: 6564441. View

10.

Sawchenko P, Swanson L . Localization, colocalization, and plasticity of corticotropin-releasing factor immunoreactivity in rat brain. Fed Proc. 1985; 44(1 Pt 2):221-7. View

11.

Sofroniew M . Direct reciprocal connections between the bed nucleus of the stria terminalis and dorsomedial medulla oblongata: evidence from immunohistochemical detection of tracer proteins. J Comp Neurol. 1983; 213(4):399-405. DOI: 10.1002/cne.902130404. View

12.

Gray T, Magnuson D . Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat. Peptides. 1992; 13(3):451-60. DOI: 10.1016/0196-9781(92)90074-d. View

13.

Liang K, Lee E . Intra-amygdala injections of corticotropin releasing factor facilitate inhibitory avoidance learning and reduce exploratory behavior in rats. Psychopharmacology (Berl). 1988; 96(2):232-6. DOI: 10.1007/BF00177566. View

14.

DE SOUZA E, PERRIN M, Insel T, Rivier J, Vale W, Kuhar M . Corticotropin-releasing factor receptors in rat forebrain: autoradiographic identification. Science. 1984; 224(4656):1449-51. DOI: 10.1126/science.6328656. View

15.

Gray T, Magnuson D . Neuropeptide neuronal efferents from the bed nucleus of the stria terminalis and central amygdaloid nucleus to the dorsal vagal complex in the rat. J Comp Neurol. 1987; 262(3):365-74. DOI: 10.1002/cne.902620304. View

16.

Charney D, Deutch A, Krystal J, Southwick S, Davis M . Psychobiologic mechanisms of posttraumatic stress disorder. Arch Gen Psychiatry. 1993; 50(4):295-305. DOI: 10.1001/archpsyc.1993.01820160064008. View

17.

Gray T, Piechowski R, Yracheta J, Rittenhouse P, Bethea C, Van de Kar L . Ibotenic acid lesions in the bed nucleus of the stria terminalis attenuate conditioned stress-induced increases in prolactin, ACTH and corticosterone. Neuroendocrinology. 1993; 57(3):517-24. DOI: 10.1159/000126400. View

18.

Canteras N, Swanson L . Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat. J Comp Neurol. 1992; 324(2):180-94. DOI: 10.1002/cne.903240204. View

19.

ARATO M, Banki C, Bissette G, Nemeroff C . Elevated CSF CRF in suicide victims. Biol Psychiatry. 1989; 25(3):355-9. DOI: 10.1016/0006-3223(89)90183-2. View

20.

Nemeroff C, Widerlov E, Bissette G, Walleus H, Karlsson I, Eklund K . Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science. 1984; 226(4680):1342-4. DOI: 10.1126/science.6334362. View