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Using optogenetics and neural tracing methods, scientists mapped the fight-or-flight reflex circuit in the brains of mice.

Neuroscientists from the Chinese Academy of Sciences have mapped the brain circuit underlying fight-or-flight fear response in mice using optogentics and neural tracing methods. Their work, published in Science, identified the neural substrate responsible for this innate fear response, and shed light on its processing between the eye and amgydala, the fear center of the brain.

Fight-or-flight response is an important fear reflex when faced with mortal danger of a looming predator. This fear reflex helps animals to either run from danger (flight) or engage in combat with the enemy (fight). Although this fear reflex is pivotal for survival, the neural mechanism underlying its processing in the brain remained largely unknown.

To start cracking this problem, the research group headed by Professor Cao Peng first activated all neurons in the superior colliculus-a structure that receives retinal inputs in the brain-by optogenetics. They found that the mice displayed escaping and freezing fear responses with such stimulation.

They went on to systematically activate different neuronal populations in the superior colliculus, and found that activation of neurons expressing parvalbumin (PV) resulted in the same fear response.

The researchers then asked if these PV neurons would respond to an incoming looming visual input. To address this question, they recorded the neuronal activity in the superior colliculus when the animals were presented a virtual incoming soccer ball. They observed that this was sufficient to provoke strong activity in the PV neurons, showing that this pathway is the bridge between incoming visual inputs and fear processing.

The authors also mapped the projections of PV neurons using virus tracing technique to three distinct regions in the brains, including the parabigeminal nucleus, which led to the amgydala. Activation of the parabigeminal pathway resulted in the same fear response as PV neuron activation in the superior colliculus.

Interestingly, they found differences in the fear response between male and female mice. They saw that male mice were more prone to freezing (analogous to fighting) while female mice were more likely to escape.

Although they did not see a difference in the neural hardwiring between male and female mice in this fear circuit, they speculated that there might be differences in the amgydala and hypothalamus of the male and female brain, giving rise to the differing responses.

This work is the first to identify the neural substrate of the fight-or-flight survival reflex in mice. It remains to be established if the same pathway exists in humans, and whether dysfunctions in this pathway is linked to any mental disorders. The article can be found at: Shang et al. (2015) A Parvalbumin-Positive Excitatory Visual Pathway to Trigger Fear Responses in Mice.

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