Neurobiology of Fear #1

Expression of defensive behaviors varies with intensity of danger

• Predators consuming prey go through procurement, pursuit and strike
• Prey have adapted to these predator behaviors with anxiety, fear and panic-related behaviors (increasing intensity of danger)

++ anxiety and fear related behaviors our kinds of expressions of defensive behavior of animals have when they are facing danger and threatening situation.

++ lots of research has been done in mice and rats because they are prey animals. Their primary defensive behaviors is to protect against predators (hide and escape rather than fighting)

++ when predators try to get prey, they go through three phases (procurement, pursuit, and strike) and prey

Procurement (lion - observe that there are lots of zebras near the lake, so i should go there)

Pursuit 추격(weaker zebra this location, .?)

Strike  (strike the prey and attempt to eat or sth)

++ these three defensive states are mediated by different neuro mechanisms and different brain regions

 

 

Different circuits mediate response to various levels of threat

++ three different defensive states are elicited by different amounts of danger, the danger could be distance from the predator, or probability of threat occuring.

++ (more or fewer shocks) - fewer shocks elicit anxiety that controlled by prefrontal cortex and amygdala then freezing behavior is largely mediated by amygdala /and escape behavior is mediated by brainstem (periaqueductul gray)

 

 

Mouse exposed to a live predator escapes near the rat and freezes far from the rat

++ (rat eat mice) mouse slowly approaching to rat, when near the rat gets scared -> escape behavior (most intensive behavior panic) - more far away (freeze to avoid visual detection from the rat)

++ different things happen depending on the distance from the rat

++ different behaviors are mediated by different regions of the brain

 

 

Characterization of predator exposure assays

++ freezing happens when the mouse is far away from the rat. / In the middle, approaching to the rat(rist-assessment위험도 분석), mouse gets elongated, they try to sense smell/ when near the rat, escape behavior

++ when exposed to control object (toy rat), none of those behaviors are shown

 

 

Escape induced by close proximity(가까움) to a live predator

++ we can change the pattern of behavior based on control of the geometry of the environment (ex. Make other situation that Rat is very near the mouse, and there is not enouch spaces to escape - too close to freeze for visual detection, the rat already saw the mouse)

++ primary behavior that mouse does is escaping. When the rat is near the mouse and the mouse escapes like climbing the wall

++ when the danger is alway intense bc the rat is too close to the mouse, then primary behavior is escaping

++ when there are more room to hide, then the primary behavior is freeze and stay away from the rat

 

 

Periaqueductual gray (PAG) drives defensive responses

• PAG consists of sausage-like columns that surround the aqueduct(송수로) in the midbrain and brainstem
• PAG contains neural circuits that perform a variety of different funcitons, many of which are involved in defensive "fight-or-flight"(투쟁-도피 반응) behaviors:
• Dorsal (dPAG) and ventral (vPAG) columns drive competing defensive responses

++ these freezing and flight are controlled by different subregions within periaqueductal gray regions. PAG has this name bc it is surrounding aqueduct which is one of fluid-filled chamber. PAG can be divdied into dorsal and ventral part.

++ stimulation of dorsal part causes escape behaviors / stimulation of ventral part causes freezing behavior.

++ stimulate this regions, bc also some attempts to electrical stimulates dorsal PAG bc also controls analgesia, and then the idea was stimulating this region we can cause analgesia in the person and he will be able to control symptoms like chronic back pain..

++10:30 even in human, this region is related to panic bc stimulating this region to try to get analgesia, it actually provoke the full dlkjl panic attack. "i feel like sth chasing me" "catastrophic fear of dying" - even though there's not anything chasing them, they still have unpleasant feeling???????

 

 

Optogenetic activation of vPAG and dPAG cause freezing and flight, respectively

++ what happens if you stimulate those regions in mouse. Optogenetic activate :

++ ventral part(freezing), when the light is on, mouse freezes

++ dorsal part(flight), when the mouse reaches the red region, the light will be turned on. It will provoke the rapid escape to far away from the red region.

 

 

Innate anxiety can be measured by avoidance of open spaces and bright lights

• Mice spend relatively more time walking in the periphery in the open field test, and avoid the center of the field

++ anxiety behavior happen in this lower threat situation, and rice and mice will high in the corner of the bed and inside of newspaper (innate anxiety related behavior) avoidance of bright light and open spaces which make them more vulnerable to predators

 

 

Pavlovian Fear Conditioning

• People and animals can be trained to be afraid of cues that predict danger, a process known as Pavlovian fear conditioning

++ learned fear conditioning behavior - pairing auditory tone to shock. After several trials, play only the tone -> rat will freeze to the auditory tone that is previously paired. The auditory tone

 

 

Building a bridge from "ear" to "fear" (or freezing)

• Via what pathway does auditory information reach the vPAG so that a fear conditioned CS can trigger a freezing response after is has been paired with an aversive US?
• In which part (or parts) of this pathway do synapses change their strength when the CS is paired with the US?

++ auditory tone eventually freezing provoking region in the brainstem(which is not part of auditory pathway) - how is thig happening