April Flowers for redOrbit.com – Your Universe Online
A noise in the dark, a rustle in the undergrowth; these are sounds likely to make an animal or a person stop sharply and be still, anticipating a predator. Freezing is part of the natural fear response, a reaction to a stimulus in the environment and part of how the brain decides whether to be afraid of it.
A new study released by a neuroscience group at Cold Spring Harbor Laboratory (CSHL) examines how fear responses are learned, controlled and memorized, showing that a particular class of neurons in a subdivision of the amygdala place an active role in these processes.
Prior studies indicated that structures inside the amygdalae — a pair of almond-shaped formations that sit deep within the brain and are known to be involved in reward-based behaviors and emotions — might be part of the circuit controlling fear and memory. The central amygdala, or CeA, was believed to be a passive relay for the signal passed within this circuit.
The findings of this new study were released in a recent issue of Nature Neuroscience.
Assistant Professor Bo Li Ph.D.’s research group became intrigued when they observed that neurons in a region of the CeA called the lateral subdivision, or CeL, “lit up” while they were studying this circuit in a particular strain of mice.
“Neuroscientists believed that changes in the strength of the connections onto neurons in the central amygdala must occur for fear memory to be encoded,” Li says, “but nobody had been able to actually show this.”
In their investigation, the team started to ask the question: If the central amygdala stores fear memory, how is that memory trace read out and translated into fear responses?
The team trained a strain of mice to respond in a Pavlovian manner to auditory cues, in order to examine the behavior of the animals undergoing a fear test. When the mice heard one of the sounds they had been taught to fear, they began to “freeze,” a very common fear response.
The team wanted to study the particular neurons involved. They employed several methods to do this, and to understand the neurons in relation to the fear-inducing auditory cue. One method involved delivering a gene that encodes for a light-sensitive protein into the specific neurons they wanted to examine.
The team then implanted a very thin fiber-optic cable directly into the area with the photosensitive neurons. This allowed them to shine colored laser light with pinpoint accuracy onto the cells, activating them. This technique is known as optogenetics. Changes in the behavior of the mice in response to the laser were monitored.
Because there are two sets of neurons important in fear-learning and memory processes, the ability to probe genetically defined groups of neurons was vital. The team learned that the difference between the neuron sets was in the release of their message-carrying neurotransmitters into the spaces called synapses between neurons. Neurotransmitter release was enhanced in one subset and diminished in another. If, instead of this specific location study, measurements had been taken across the total cell population in the central amygdala, the levels of neurotransmitters from these two sets would have averaged out and not been detected.
Li and his colleagues found that fear conditioning induced experience-dependent changes in the release of neurotransmitters in excitatory synapses connected to inhibitory neurons, which are neurons that suppress the activity of other neurons, in the CeA. Changes in the strength of neuronal connections such as these are called synaptic plasticity.
Somatostatin-positive (SOM+) neurons are particularly important in this process as somatostatin is a hormone that affects the release of neurotransmitters. The scientists found that fear-memory formation was impaired when the activation of SOM+ neurons was prevented.
They also found that SOM+ neurons are necessary for recall of fear memories. The activity of these neurons alone is sufficient, they found, to drive fear responses. The team’s work demonstrates that the central amygdala is an active component, and is driven by input from the lateral amygdala, to which it is connected instead of being a passive relay for the signals driving fear learning and responses in mice.
“We find that the fear memory in the central amygdala can modify the circuit in a way that translates into action — or what we call the fear response,” explains Li.
Li and his colleagues are planning future research to understand how these processes may be altered in post-traumatic stress disorder (PTSD) and other disorders involving abnormal fear learning. One goal of this research is to develop pharmacological interventions for such disorders. Li is hopeful that with the discovery of specific cellular markers with techniques such as optogenetics, a breakthrough is possible.
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