Background
Safety signals exert a powerful buffering effect when provided during exposure to
uncontrollable stressors. We evaluated the role of the sensory insular cortex (Si)
and the extend amygdala in this “safety signal effect.”
Methods
Rats were implanted with microinjection cannula, exposed to inescapable tailshocks
either with or without a safety signal, and later tested for anxiety-like behavior
or neuronal Fos expression.
Results
Exposure to the uncontrollable stressor reduced later social exploration but not when
safety signals were present. Temporary inhibition of Si during stressor exposure but
not during later behavioral testing blocked the safety signal effect on social exploration.
The stressor induced Fos in all regions of the amygdala, but safety signals significantly
reduced the number of Fos immunoreactive cells in the basolateral amygdala and ventrolateral
region of the bed nucleus of the stria terminalis (BNSTlv). Inhibition of BNSTlv neuronal
activity during uncontrollable stressor exposure prevented the later reduction in
social exploration. Finally, safety signals reduced the time spent freezing during
uncontrollable stress.
Conclusions
These data suggest that safety signals inhibit the neural fear or anxiety response
that normally occurs during uncontrollable stressors and that inhibition of the BNSTlv
is sufficient to prevent later anxiety. These data lend support to a growing body
of evidence that chronic fear is mediated in the basolateral amygdala and BNSTlv and
that environmental factors that modulate fear during stress will alter the long-term
consequences of the stressor.
Key Words
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References
- Phenomonology of anxiety disorders.in: Blanchard R.J. Blanchard D.C. Griebel G. Nutt D. Handbook of Anxiety and Fear. 1st ed. Associated Press, Amsterdam2008: 365-393
- Posttraumatic stress disorder may be associated with impaired fear inhibition: Relation to symptom severity.Psychiatry Res. 2009; 167: 151-160
- Changing fear: The neurocircuitry of emotion regulation.Neuropsychopharmacology. 2010; 35: 136-146
- Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear.Neuroscience. 2007; 146: 1495-1503
- Stress-induced enhancement of fear learning: An animal model of posttraumatic stress disorder.Neurosci Biobehav Rev. 2005; 29: 1207-1223
- Lesions of the basolateral amygdala reverse the long-lasting interference with shuttle box escape produced by uncontrollable stress.Behav Brain Res. 2010; 211: 71-76
- The role of prior stressor controllability and the dorsal raphe nucleus in sucrose preference and social exploration.Behav Brain Res. 2008; 193: 87-93
- Fear conditioned with escapable and inescapable shock: Effects of a feedback stimulus.J Exp Psychol Anim Behav Process. 1984; 10: 307-323
- The sensory insular cortex mediates the stress-buffering effects of safety signals but not behavioral control.J Neurosci. 2008; 28: 13703-13711
- Shock signals and the development of stress-induced analgesia.J Exp Psychol Anim Behav Process. 1987; 13: 226-238
- Conditioned inhibition and the UCS-CS interval.Anim Learn Behav. 1976; 4: 217-220
- Modeling signal features of escape response: Effects of cessation conditioning in “learned helplessness” paradigm.J Exp Psychol Anim Behav Processes. 1990; 16: 123-136
- Effects of coping behavior with and without a feedback signal on stress pathology in rats.J Comp Physiol Psychol. 1971; 77: 22-30
- Auditory, somatosensory, and multisensory insular cortex in the rat.Cereb Cortex. 2008; 18: 2941-2951
- 5-hydroxytryptamine 2C receptors in the basolateral amygdala are involved in the expression of anxiety after uncontrollable traumatic stress.Biol Psychiatry. 2010; 67: 339-345
- Chemical lesion of the bed nucleus of the stria terminalis blocks the behavioral consequences of uncontrollable stress.Behav Neurosci. 2004; 118: 443-448
- The role of the amygdala and dorsal raphe nucleus in mediating the behavioral consequences of inescapable shock.Behav Neurosci. 1993; 107: 377-388
- Phasic vs sustained fear in rats and humans: Role of the extended amygdala in fear vs anxiety.Neuropsychopharmacology. 2010; 35: 105-135
- The Rat Brain in Stereotaxic Coordinates.4th ed. Academic Press, New York1998
- Medial prefrontal cortical activation modulates the impact of controllable and uncontrollable stressor exposure on a social exploration test of anxiety in the rat.Stress. 2009; 12: 445-450
- A review of 25 years of the social interaction test.Eur J Pharmacol. 2003; 463: 35-53
- c-Fos as a transcription factor: A stressful (re)view from a functional map.Neurochem Int. 1998; 33: 287-297
- Glutamate receptor agonists increase the expression of Fos, Fra, and AP-1 DNA binding activity in the mammalian brain.J Neurosci Res. 1989; 24: 72-80
- Activation of phenotypically distinct neuronal subpopulations in the anterior subdivision of the rat basolateral amygdala following acute and repeated stress.J Comp Neurol. 2008; 508: 458-472
- Conditioned and unconditional components of post-shock freezing.Pavlov J Biol Sci. 1980; 15: 177-182
- Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review.Neurosci Biobehav Rev. 2006; 30: 188-202
- LTP is accompanied by commensurate enhancement of auditory-evoked responses in a fear conditioning circuit.Neuron. 1995; 15: 127-136
- Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse.Neuron. 2005; 46: 309-320
- Fear and safety learning differentially affect synapse size and dendritic translation in the lateral amygdala.Proc Natl Acad Sci U S A. 2010; 107: 9418-9423
- Synaptic correlates of fear extinction in the amygdala.Nat Neurosci. 2010; 13: 489-494
- Cascade projections from somatosensory cortex to the rat basolateral amygdala via the parietal insular cortex.J Comp Neurol. 1998; 399: 469-491
- Cortical afferents to the extended amygdala.Ann N Y Acad Sci. 1999; 877: 309-338
- Pain pathways involved in fear conditioning measured with fear-potentiated startle: Lesion studies.J Neurosci. 1999; 19: 420-430
- Dissociating pain from its anticipation in the human brain.Science. 1999; 284: 1979-1981
- Activation of the left amygdala to a cognitive representation of fear.Nat Neurosci. 2001; 4: 437-441
- Equipotentiality of thalamo-amygdala and thalamo-cortico-amygdala circuits in auditory fear conditioning.J Neurosci. 1992; 12: 4501-4509
Article info
Publication history
Published online: June 20, 2011
Accepted:
April 6,
2011
Received in revised form:
March 11,
2011
Received:
October 26,
2010
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
