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Coping with Danger: The Neural Basis of Defensive Behavior and Fearful Feelings

Kevin S. Labar, Joseph E. Ledoux

10.1002/cphy.cp070408

Source: Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Fear Conditioning
2 The Neural System Mediating Conditioned Fear Responses
2.1 Input Pathways
2.2 Output Pathways
3 Assessing Dangerous Environmental Contexts
4 Cortical Control of Fearful and Defensive Behavior
5 Fear Conditioning in Humans
6 Cellular Mechanisms Involved in Fear Conditioning
6.1 Electrophysiological Studies
6.2 Long‐Term Potentiation
7 Stress and Fear Circuits
8 From Evolutionary Reaction to Cognitive Coping
9 Defensive Behaviors and Fearful Feelings
10 Summary
Figure 1. Figure 1.

Classical conditioning paradigm. The time line for three acquisition and three extinction trials is depicted. CS, conditioned stimulus; US, unconditioned stimulus.
Figure 2. Figure 2.

Neural pathways of conditioned fear. Parallel projections from increasingly complex sensory processing areas are funneled through the lateral nucleus, integrated, and combined with inputs reaching the basal nuclei. Neocortical feedback projections (dashed lines) originate primarily from these nuclei. Intraamygdaloid processing is directed toward the central nucleus, which coordinates brain stem systems involved in defensive reactions and arousal. ACC BASAL, accessory basal nucleus; BNST, bed nucleus of the stria terminalis; RPC, nucleus reticularis pontis caudalis; RVL, rostral ventrolateral medullary nuclei.
Figure 3. Figure 3.

Dissociable contributions of the amygdala and hippocampus to cued and contextual fear. In contrast to both nonlesioned (a) and cortex‐lesioned (b) controls, rats with amygdaloid lesions (c) do not acquire conditioned freezing responses to either the explicit conditioned stimulus (CS) or contextual cues (pre‐CS). Hippocampal lesions (d) interfere selectively with conditioned fear responses to the context.

From Phillips and LeDoux 125 with permission
Figure 4. Figure 4.

Ventromedial prefrontal cortical lesions prolong the extinction of conditioned fear. Rats with pretraining lesions of the ventromedial prefrontal cortex (mPFC) took longer to extinguish a conditioned freezing response to an explicit conditioned stimulus (CS) than rats with sham lesions or unoperated controls. Extinction to contextual cues alone (pre‐CS) was comparable across all groups.

From Morgan et al. 108 with permission
Figure 5. Figure 5.

Impaired fear conditioning in temporal lobectomy patients. Difference skin conductance response (SCR) scores above 0 reflect intact discrimination performance during acquisition training. In contrast to both nonsurgical controls and epileptic controls with excision of other brain regions, temporal lobectomy patients exhibit impaired conditioned SCR acquisition. Scores are collapsed across trials within each experimental phase. μS, microsiemens.

From LaBar et al. 74 with permission
Figure 6. Figure 6.

Conditioning‐induced changes in simultaneously recorded unit responses in the lateral amygdala. Cross‐correlograms indicate (A) a conditioning‐induced direct interaction between lateral amygdaloid neurons with a latency of 3 ms (double arrows). This interaction was reversed following extinction training. In addition, conditioning‐induced synchronous firing between lateral amygdaloid neurons (synchronicity peak denoted by t = 0), which persisted following 30 trials of extinction training (B). This latter finding suggests that the lateral nucleus has access to an extinction‐resistant memory trace for the conditioning episode. Dashed line indicates a confidence interval of P<0.01. Bin width is 0.5 ms in A and 5.0 ms in B. LA, lateral amygdala.

From Quirk et al. 130 with permission
Figure 7. Figure 7.

Long‐term potentiation enhances auditory responses in the lateral nucleus of the amygdala. High‐frequency electrical stimulation of the auditory thalamus (medial portion of the medial geniculate and posterior intralaminar nuclei) induced long‐term potentiation of electrically evoked field potentials and a corresponding long‐lasting enhancement of auditory‐evoked responses in the lateral amygdala. Such posttreatment effects were not evident following low‐frequency control stimulation.

From Rogan and LeDoux 131 with permission
Figure 8. Figure 8.

Limbic forebrain regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis. Whereas the amygdala exerts a positive influence over the HPA axis, the hippocampus and medial prefrontal cortex (mPFC) exert a counteractive negative influence. BNST, bed nucleus of the stria terminalis; PVN, paraventricular nucleus of the hypothalamus; CRF, corticotropin‐releasing factor; ACTH, corticotropin.


Figure 1.

Classical conditioning paradigm. The time line for three acquisition and three extinction trials is depicted. CS, conditioned stimulus; US, unconditioned stimulus.



Figure 2.

Neural pathways of conditioned fear. Parallel projections from increasingly complex sensory processing areas are funneled through the lateral nucleus, integrated, and combined with inputs reaching the basal nuclei. Neocortical feedback projections (dashed lines) originate primarily from these nuclei. Intraamygdaloid processing is directed toward the central nucleus, which coordinates brain stem systems involved in defensive reactions and arousal. ACC BASAL, accessory basal nucleus; BNST, bed nucleus of the stria terminalis; RPC, nucleus reticularis pontis caudalis; RVL, rostral ventrolateral medullary nuclei.



Figure 3.

Dissociable contributions of the amygdala and hippocampus to cued and contextual fear. In contrast to both nonlesioned (a) and cortex‐lesioned (b) controls, rats with amygdaloid lesions (c) do not acquire conditioned freezing responses to either the explicit conditioned stimulus (CS) or contextual cues (pre‐CS). Hippocampal lesions (d) interfere selectively with conditioned fear responses to the context.

From Phillips and LeDoux 125 with permission


Figure 4.

Ventromedial prefrontal cortical lesions prolong the extinction of conditioned fear. Rats with pretraining lesions of the ventromedial prefrontal cortex (mPFC) took longer to extinguish a conditioned freezing response to an explicit conditioned stimulus (CS) than rats with sham lesions or unoperated controls. Extinction to contextual cues alone (pre‐CS) was comparable across all groups.

From Morgan et al. 108 with permission


Figure 5.

Impaired fear conditioning in temporal lobectomy patients. Difference skin conductance response (SCR) scores above 0 reflect intact discrimination performance during acquisition training. In contrast to both nonsurgical controls and epileptic controls with excision of other brain regions, temporal lobectomy patients exhibit impaired conditioned SCR acquisition. Scores are collapsed across trials within each experimental phase. μS, microsiemens.

From LaBar et al. 74 with permission


Figure 6.

Conditioning‐induced changes in simultaneously recorded unit responses in the lateral amygdala. Cross‐correlograms indicate (A) a conditioning‐induced direct interaction between lateral amygdaloid neurons with a latency of 3 ms (double arrows). This interaction was reversed following extinction training. In addition, conditioning‐induced synchronous firing between lateral amygdaloid neurons (synchronicity peak denoted by t = 0), which persisted following 30 trials of extinction training (B). This latter finding suggests that the lateral nucleus has access to an extinction‐resistant memory trace for the conditioning episode. Dashed line indicates a confidence interval of P<0.01. Bin width is 0.5 ms in A and 5.0 ms in B. LA, lateral amygdala.

From Quirk et al. 130 with permission


Figure 7.

Long‐term potentiation enhances auditory responses in the lateral nucleus of the amygdala. High‐frequency electrical stimulation of the auditory thalamus (medial portion of the medial geniculate and posterior intralaminar nuclei) induced long‐term potentiation of electrically evoked field potentials and a corresponding long‐lasting enhancement of auditory‐evoked responses in the lateral amygdala. Such posttreatment effects were not evident following low‐frequency control stimulation.

From Rogan and LeDoux 131 with permission


Figure 8.

Limbic forebrain regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis. Whereas the amygdala exerts a positive influence over the HPA axis, the hippocampus and medial prefrontal cortex (mPFC) exert a counteractive negative influence. BNST, bed nucleus of the stria terminalis; PVN, paraventricular nucleus of the hypothalamus; CRF, corticotropin‐releasing factor; ACTH, corticotropin.

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Article Title: Coping with Danger: The Neural Basis of Defensive Behavior and Fearful Feelings
 

How to Cite

Kevin S. Labar, Joseph E. Ledoux. Coping with Danger: The Neural Basis of Defensive Behavior and Fearful Feelings. Compr Physiol 2011, Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms: 139-154. First published in print 2001. doi: 10.1002/cphy.cp070408