Read more about this study in Nature Neuroscience
A pair of small almond-shaped structures called the amygdalae are often said to be the human brain’s “fear centers.” Many experiments have shown their involvement in the fear response—a complex series of biological processes that are set in motion when we are, for instance, startled or perceive a threat in our environment. Disorders involving the fear response include post-traumatic stress disorder (PTSD), where fear is experienced in the absence of an immediate threat (often via the involuntary recall of traumatic memories).
But how are fear memories stored and in which nerve cells, exactly? These questions were central to research published this week in Nature Neuroscience, conducted by a team at Cold Spring Harbor Laboratory on Long Island, led by NARSAD Young Investigator Grantee Bo Li, Ph.D. and including NARSAD Distinguished Investigator Grantee Z. Josh Huang, Ph.D. and NARSAD Young Investigator Grantee Hiroki Taniguchi, Ph.D.
By training mice to respond in Pavlovian fashion to fear cues, and using technology called optogenetics first introduced by Foundation Scientific Council Member Karl Deisseroth, M.D., Ph.D.—which makes it possible to switch individually selected neurons “on” and “off” with beams of colored laser light—the scientists were able to pick apart the process by which stored fear memories are “read out” and translated into physiological fear responses.
Li’s group found that fear conditioning induced changes in the central amygdala, in the release of neurotransmitters in excitatory synapses that connect with inhibitory neurons—neurons that suppress the activity of other neurons. These changes in the strength of neuronal connections are known as synaptic plasticity. Particularly important, they discovered, were somatostatin-positive (SOM+) neurons. Somatostatin is a hormone that affects neurotransmitter release. Li and colleagues found that fear-memory formation was impaired when they prevented activation of SOM+ neurons.
SOM+ neurons are necessary for recall of fear memories, the team also found. Indeed, the activity of these neurons alone proved sufficient to drive fear responses. The team’s work demonstrates that the central amygdala is an active component in fear, and is driven by input from the lateral amygdala, to which it is connected. These discoveries support the team’s longer term goal of discovering points of intervention for new therapeutics.