One chapter in Water Margin, one of China’s four great classical novels, describes WU Song’s fight with a tiger. Words such as "immediately turned," "dodged," "evaded," "jumped," "grabbed," etc. capture the character’s psychological changes and physiological responses when facing danger. 

In psychology, this is known as the “fight or flight” response and refers to the body’s reaction to a perceived threat or danger – i.e., its preparation either to physically fight the danger or run away from it. As part of this process, certain hormones, such as adrenalin and cortisol, are released, speeding the heart rate, slowing digestion, shunting blood flow to major muscle groups, and changing various other autonomic nervous functions, giving the body a burst of energy and strength.  

When the perceived threat is gone, systems are designed to return to normal function via the relaxation response. As we all know, when in danger, it’s natural to feel afraid. This fear triggers many split-second changes in the body to prepare to defend against the danger or to avoid it. This “fight or flight” response is a healthy reaction meant to protect a person from harm. 

However, if people suffer excessively or repeatedly from the fight or flight response, it is bound to damage their health. This condition is defined as post-traumatic stress disorder (PTSD). People who suffer from PTSD may feel stressed or frightened even when they’re no longer in danger. PTSD was first brought to public attention in relation to war veterans, but it can result from a variety of traumatic incidents, such as mugging, rape, torture, being kidnapped or held captive, child abuse, car accidents, train wrecks, plane crashes, bombings, or natural disasters such as floods or earthquakes.  

Nowadays, PTSD has grown to be one of the hot topics in brain science. It is believed that the neural circuits causing the fight or flight response may be the source of PTSD pathogenesis. Yet little is known about the neural circuits specifically processing threat-relevant sensory information in the mammalian brain. 

In a new study published on June 26 in Science, a research group led by Professor CAO Peng of the Institute of Biophysics, Chinese Academy of Sciences, has made great progress in understanding the parvalbumin-positive excitatory visual pathway that triggers the fight or flight response in mice. 

By making use of an optogenetic approach, the research team found that activation of neurons expressing channelrhodopsin-2 (ChR2) in the superior colliculus in mice caused freezing. This encouraged the researchers’ systematic identification of the key neuronal subtypes underlying that behavior. 

The researchers found that parvalbumin-positive (PV+) excitatory projection neurons in the mouse superior colliculus are (SC) a key neuronal subtype for detecting looming objects and triggering the fight or flight response. These neurons, which are distributed mainly in the superficial superior colliculus (SC), divergently project into different brain areas, including the parabigeminal nucleus (PBG), namely, an intermediate station leading to the amygdala. Activation of the PV+ SC-PBG pathway caused a fight or flight response, induced conditioned aversion and resulted in depression-like behaviors. 

Researchers conclude that the SC PV+ neurons form a subcortical visual pathway that transmits threat-related visual information to the amygdala to cause fear responses, suggesting a “retina-SC-PBGN-amygdala hypothalamus” pathway for vision-induced fear responses.  

In addition, the SC PV+ neurons in the superficial gray layer are predominantly glutamatergic projection neurons with spiking patterns distinct from those of their counterparts in cortical regions. This finding broadens the concept of PV+ neurons and adds another perspective to understanding their function.  

Last but not least, the SC PV+ neurons may belong to the type-ρ looming detector category, supporting the notion that mathematically defined computational units correspond to specific neuronal subtypes. These outcomes lay a solid theoretical foundation for further study of PTSD pathogenesis. 

Fig. A) PV+ neurons detect soccer ball-like looming stimulus in the visual field. B) The morphological and physiological properties of PV+ neurons in SC. C) The downstream pathways formed by PV+ neurons in SC (Image by CAO Peng)