Amygdala microcircuits mediating fear expression and extinction

doi:10.1016/j.conb.2012.02.014

Current Opinion in Neurobiology

Volume 22, Issue 4, August 2012, Pages 717-723

https://doi.org/10.1016/j.conb.2012.02.014 Get rights and content

This review summarizes the latest developments in our understanding of amygdala networks that support classical fear conditioning, the experimental paradigm most commonly used to study learned fear in the laboratory. These recent advances have considerable translational significance as congruent findings from studies of fear learning in animals and humans indicate that anxiety disorders result from abnormalities in the mechanisms that normally regulate conditioned fear. Because of the introduction of new techniques and the continued use of traditional approaches, it is becoming clear that conditioned fear involves much more complex networks than initially believed, including coordinated interactions between multiple excitatory and inhibitory circuits within the amygdala.

Highlights

► Transmission of information about conditioned stimuli from the lateral amygdala to fear output neurons in the central medial amygdala is indirect. ► Glutamatergic basal amygdala neurons connect the input and output stations of the amygdala for conditioned fear. ► Multiple interacting layers of inhibition control fear output neurons in the central medial nucleus of the amygdala. ► Fear extinction depends on multiple parallel mechanisms.

Section snippets

Transmission of CS information from LA to fear output Ce neurons

While the original model invoked direct projections from LA to Ce, and from there, to fear effector neurons (Figure 1a), it was pointed out [9] that there are no direct links between LA, the main point of entry for thalamic and cortical information about CSs [10, 11], and the medial sector of Ce (CeM), contributing most amygdala projections to brainstem fear effectors (Figure 1b) [12, 13]. These results suggested that downstream of LA, was one or more population(s) of cells relaying CS

Multiple interacting layers of inhibition control CeM fear output neurons

As mentioned above, the contrasting effects of pre-training versus post-training BA lesions suggest that besides BA, there is an additional relay between LA and CeM. The possibility that CeL neurons performed this function was initially dismissed because they were expected to generate a feed-forward inhibition of CeM. However, recent findings suggest that this reasoning might be incorrect. Below, we summarize the organization of inhibitory inputs to CeM and then consider their contribution to

Fear extinction depends on multiple parallel mechanisms

The CS responsiveness of CeM neurons closely parallels fear expression levels [16••, 17••] and is reduced by extinction training [17^••].²

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgments

We thank our colleagues, Drs. Taiju Amano, Alon Amir, and Daniela Popa, for their vital contributions to many of the experiments described here. This work was supported by R01 grant MH-083710 from NIMH.

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View full text

Amygdala microcircuits mediating fear expression and extinction

Highlights

Section snippets

Transmission of CS information from LA to fear output Ce neurons

Multiple interacting layers of inhibition control CeM fear output neurons

Fear extinction depends on multiple parallel mechanisms

References and recommended reading

Acknowledgments

Nature

J Neurosci

Exp Brain Res

J Neurosci

Nat Neurosci

Neuron

J Neurosci

J Neurosci

Eur J Neurosci

Nat Neurosci

Emotional memory: in search of systems and synapses

Ann NY Acad Sci

Pharmacological analysis of fear-potentiated startle

Braz J Med Biol Res

Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear

Physiol Rev

The medial geniculate, not the amygdala, as the root of auditory fear conditioning

Hear Res

Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala

Nature

A neural switch for active and passive fear

Neuron

Prefrontal control of fear: more than just extinction

Curr Opin Neurobiol

Intra-amygdaloid projections of the lateral nucleus in the cat: PHA-L anterograde labeling combined with post-embedding GABA and glutamate immunocytochemistry

J Comp Neurol

Somatosensory and auditory convergence in the lateral nucleus of the amygdala

Behav Neurosci

The organization of projections from the central nucleus of the amygdala to brainstem sites involved in central autonomic regulation: a combined retrograde transport-immunohistochemical study

Brain Res

A description of the amygdaloid complex in the rat and cat with observations on intra-amygdaloid axonal connections

J Comp Neurol

Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala

Trends Neurosci

Encoding of conditioned fear in central amygdala circuits

Nature

Lesions of the basal amygdala block expression of conditioned fear but not extinction

J Neurosci

Damage to the lateral and central, but not other, amygdaloid nuclei prevents the acquisition of auditory fear conditioning

Learn Mem