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J Neurosci. 2016 Jun 15;36(24):6488-96. doi: 10.1523/JNEUROSCI.4419-15.2016.

Central Amygdala Somatostatin Neurons Gate Passive and Active Defensive Behaviors.

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Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and.
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon 1400-038, Portugal.
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and


The central amygdala (CeA) has a key role in learning and expression of defensive responses. Recent studies indicate that somatostatin-expressing (SOM(+)) neurons in the lateral division of the CeA (CeL) are essential for the acquisition and recall of conditioned freezing behavior, which has been used as an index of defensive response in laboratory animals during Pavlovian fear conditioning. However, how exactly these neurons participate in fear conditioning and whether they contribute to the generation of defensive responses other than freezing remain unknown. Here, using fiber-optic photometry combined with optogenetic and molecular techniques in behaving mice, we show that SOM(+) CeL neurons are activated by threat-predicting sensory cues after fear conditioning and that activation of these neurons suppresses ongoing actions and converts an active defensive behavior to a passive response. Furthermore, inhibition of these neurons using optogenetic or molecular methods promotes active defensive behaviors. Our results provide the first in vivo evidence that SOM(+) neurons represent a CeL population that acquires learning-dependent sensory responsiveness during fear conditioning and furthermore reveal an important role of these neurons in gating passive versus active defensive behaviors in animals confronted with threat.


The ability to develop adaptive behavioral responses to threat is fundamental for survival. Recent studies indicate that the central lateral amygdala (CeL), in particular its somatostatin-expressing neurons, is crucial for both learning and the expression of defensive response. However, how exactly these neurons participate in such processes remains unclear. Here we show for the first time in behaving mice that the somatostatin-expressing neurons in the CeL acquire learning-dependent responsiveness to sensory cues predicting a threat. Furthermore, our results indicate that these neurons gate the behavioral output of an animal: whereas high activity in these neurons biases toward passive defensive responses, low activity in these neurons allows the expression of active defensive responses.


active avoidance; central amygdala; fear; fiber-optic photometry; optogenetics; somatostatin neurons

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