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Post-traumatic stress or chronic stress events can cause depression or anxiety, but in the population as a whole, a small proportion of people develop mood disordersfollowing stressful events.
As a result, most groups show resistance to stress, and a minority population shows sensitivity
.
Midbrain dopamine (DA) neurons are involved in reward processing and also in stress responses
.
DA-capable circuits in the lateral substantia nigra projection striatum tail (TS) participate in alert or responsive behavior, and DA-ergic circuits in the ventral tegmental area (VTA) project into the nucleus accumbens (NAc) engage in non-aggressive social sniffing behavior
.
On October 19, 2022, Annegret L.
Falkner's research team at the Princeton Institute of Neuroscience at Princeton University revealed stress-resistant behavioral patterns and dopamine neuronal activity signatures
.
1
Characteristics of differential behavior in resistant mice and sensitive mice
The Chronic Social Frustration Stress Model is an animal model that studies stress sensitivity and resistance, and sensitive mice that experience 10 days of stress show obvious symptoms such as social avoidance and loss of sugar water preference, while resistant mice do not exhibit this behavioral disorder.
The researchers recorded the behaviors of CD1 mice (attacker) and C57 mice (attacked) during the whole social frustration stress process through high-definition cameras and behavioral recorders, and selected four behaviors such as mutual exploration, attack, counterattack, and escape behavior for analysis, and observed the behavioral differences
between sensitive mice and resistant mice.
They found no difference in the number and duration of attacks between stress-sensitive and stress-resistant mice, but the resistant mice fought back more and spent more time in contact with the attacking mice, while the sensitive mice fled
more after the attack.
Figure 1: Behavioral strategies in stress-resistant and sensitive mice
2
DA neuronal activity characterization in stress-resistant mice
Fiber optic calcium imaging technology found that during the 10-day chronic stress, the activity of DA neurons in the TS region increased when C57 mice were close to the attacking mice, and there was a corresponding increase with the increase of the number of attack days, and the DA neuron activity decreased after leaving the attacking mice, which was shown in both male stress-sensitive and resistant mice.
In contrast, DA neuron activity in the NAc region decreased significantly when C57 mice were close to the attacking mice, and increased DA neuron activity after leaving the attacking mice
.
This change in neuronal activity was consistent
with the mice's behavior toward approaching the attacking mice and rewarding the departing attacking mice.
Based on the aforementioned monitoring of mouse behavior, the researchers concluded that sensitive mice and resistant mice showed different responses (counterattack or flight) in the face of attackers, and further calcium imaging techniques found that DA neuron activity in the NAc region of resistant mice increased when fighting back and decreased when fleeing, while sensitive mice did the opposite: weakened
when fighting back.
These results suggest that DA neuronal activity in the NAc region predicts individual differences
in sensitivity and resistance.
Figure 2: Predictable resistance to DA neuron activity in the NAc region
3
Open and closed-loop optogenetics regulate DA neuronal activity
In order to further determine the role of NAc region DA neuron activity in stress resistance and sensitivity, the researchers first used optogenetics to activate NAc region DA neurons to increase the social behavior of C57 mice and enhance stress resistance.
Second, they designed behavior-driven closed-loop optogenetic devices, in which C57 mouse counterattack behavior activates DA neuronal activity, further enhancing counterattack behavior and promoting resistance, while inhibiting DA neuronal activity in aggressive behavior does not promote stress sensitivity
.
These results suggest that DA neurons in the NAc region promote stress resistance after activation during social frustration stress
.
Figure 3: Activation of DA neurons in the NAc region promotes stress resistance
summary
In this paper, it is found that sensitive and resistant mice show completely opposite characteristics in behavioral strategies and NAc region DA neuron activity in the face of stress, and both open and closed-loop photoactivation of NAc region DA neurons can promote stress resistance
.
【References】
1.
https://doi.
org/10.
1038/s41586-022-05328-2
The images in the article are from references
