Animal studies of amygdala function in fear and uncertainty: Relevance to human research

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Abstract

This article reviews research in both animals and humans on the considerable progress made in elucidating a brain circuitry of fear, particularly the importance of the amygdala in fear conditioning. While there is considerable agreement about the participation of the amygdala in fear in both animals and humans, there are several issues about the function of the amygdala raised by the human research that have not been addressed by or may be answered by animal research. Three of these are addressed in this article: (1) is the amygdala involved in or necessary for both fear learning and unconditioned fear? (2) Does the amygdala code for intensity of fear? (3) Is the amygdala preferentially involved in fear, or is it also activated when there are no overt fear or aversive stimuli, but where the situation can be described as uncertain? We present evidence indicating that the rodent amygdala is involved in some types of fear (conditioned fear), but not all types (unconditioned fear), and may therefore have significance for a differential neurobiology of certain anxiety disorders in humans. Further, similar to the human amygdala, the rodent amygdala responds to varying intensities of aversive stimulation. Finally, it is suggested that, similar to humans, the rodent amygdala is involved in the evaluation of uncertainty. We conclude that progress on elucidating the role of the amygdala in fear is facilitated by corroboration of findings from both animal and human research.

Section snippets

Neuroanatomy of the rat amygdala

The amygdala is comprised of 13 nuclei each having numerous subnuclei (Pitkanen, 2000). From numerous neuroscience methods, some of these are known to be important for conditioned fear (Davis and Whalen, 2001, LeDoux, 2000, Maren and Quirk, 2004, Rodrigues et al., 2004). These include the basolateral complex (BLA; consisting of the lateral, basal and accessory basal nuclei) and the central nucleus of the amygdala (CeA; subdivided into the capsular, lateral and medial divisions). These nuclei

Lesions of the primate amygdala and fear

The amygdala has been linked to the emotion of fear since the pioneering studies of Kluver and Bucy in the late 1930s (Kluver and Bucy, 1939), who found that monkeys with anterior temporal lobe lesions (including the amygdala, hippocampus and surrounding cortices) had several changes in behavior and psychological processing. These changes included visual agnosia, hypermetamorphosis (increased examination of objects), hypersexuality, tameness, and reduced fearfulness. Additional research found

Human brain imaging and the amygdala

In the 1990s the use of human brain imaging technology (e.g., PET, fMRI) to explore the function of the amygdala exploded and continues at a rapid rate today. Activity in the amygdala is predominantly measured during two basic paradigms: fear conditioning and presentation of faces, but has expanded to other emotional stimuli of various modalities. Fear conditioning has confirmed the human amygdala is activated during fear learning. LaBar et al. (1998) found that increases in amygdala activity

Is the amygdala involved in fear learning and unconditioned fear?

Neuroimaging studies with normal humans and studies of humans with amygdala lesions reliably demonstrate that the amygdala is critical for emotional learning in fear conditioning paradigms (Buchel and Dolan, 2000, Davis and Whalen, 2001, Dolan, 2002, Phelps and Anderson, 1997). Other studies employing non-learning paradigms suggest that the human amygdala is critical for evaluation or interpretation of fear in a number of modalities (for review, see Zald, 2003), whether it is learned or not

Does the amygdala code for intensity of fear?

Emotional stimuli carry at least two types of information: valence and intensity. While the strongest support of the role of the amygdala has been with the negative emotion of fear, there is now sufficient evidence that the amygdala is also involved in positively valenced emotion in both humans and animals (Baxter and Murray, 2002). Recent studies in humans also suggest that the amygdala codes for intensity of emotion, but possibly not valence (Anderson et al., 2003b; Small et al., 2003). Two

Does the amygdala detect uncertainty or ambiguity?

The previous two examples of amygdala activation in rats using gene expression as a measure of activity emphasized the amygdala's involvement in explicit conditioning of fear. However, the role of the amygdala is thought not to be limited and preferentially involved in processing fear, but to play a role in appraisal during times of uncertainty and heightened vigilance (Davis and Whalen, 2001, Rosen and Schulkin, 1998, Whalen, 1998). As indicated earlier, this notion has exquisitely been

Conclusions

In this article, we have described some parallels in the role of the human and rodent amygdala in fear. Fear conditioning experiments in both humans and rodents complement each other, where lesions and activity measures (PET, fMRI in humans; gene expression in rodents) demonstrate that the amygdala plays a crucial role in this type of learning. Other types of negative affect that are not explicitly learned (presentation of negatively valenced stimuli, affect disposition) are not consistently

Acknowledgement

Supported by NSF grant IBN-0129809 awarded to J.B.R.

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