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iNature
Some people may be sluggish in the face of pressure, but some people can be optimistic about setbacks, and even become more courageous
.
After the stress experience ends, susceptible and resilient individuals show differences
in the intrinsic properties of midbrain limbic dopamine (DA) neurons.
However, the causal relationship between DA, behavioral under stress, and individual resilience differences is unclear
.
On October 19, 2022, Lindsay Willmore et al.
of Princeton University published a research paper entitled "Behavioural and dopaminergic signatures of resilience" online in Nature, which recorded DA neuronal activity simultaneously projected to the nucleus accumbens (NAc) during social failure in mice.
(giving reward signals) and striatum (TS) (signaling threats
).
Supervised and unsupervised behavior quantification showed that under stress, resilient mice and susceptible mice used different behavioral strategies and had different activity patterns (but not TS)
at the DA end of NAc.
Neurologically, resilient mice had greater activity in the vicinity of the attacker, including at the beginning of
a counterattack.
Conversely, susceptible mice had greater activity
at the onset of attack deviation and flight.
The study also performed open-loop optical genetic stimulation of NAc-projected DA neurons during failure (random timing) or timed
specific behaviors using real-time behavioral classification.
Both open-loop activation and counter-attack time activation promote resilience and reorganize behavior in failure toward resilience-related patterns
.
Together, these data provide links between
DA neural activity, resilience, and behavior associated with resilience in stressful experiences.
for depression and anxiety.
However, in the general population, only a small percentage showed these results, while others remained resilient
.
Understanding what factors make individuals tend to be resilient rather than stress sensitive is a major scientific goal
.
Previous studies using mice have focused on risk factors for susceptibility and pathology after stress, with little attention paid to the experience of
stress itself.
The midbrain dopamine (DA) system plays a vital role in the regulation of reward-based motivation and learning, and changes
in this system have been observed in post-stress animals.
In addition, modulating the system after stress can salvage the depression-like phenotype
.
However, it is unclear
whether DA plays an active role in determining outcomes during periods of stress.
Resilience and susceptibility are associated with different behavioral traits at the time of failure (Image from Nature) To understand the link between stress experience, behavior, and DA neural activity, the researchers first used recent developments in computer vision and posture tracking to accurately quantify the behavior
of mice when experiencing chronic social failure stress.
The researchers then tested whether there was a change
in the activity projected by the two DAs consistent with key behaviors under chronic stress.
The study documented the behavior
of DA neuronal activity simultaneously projecting to the nucleus accumbens (NAc) (which signals rewards) and the striatum (TS) (which signals threats) when the mice fail to socialize.
Supervised and unsupervised behavior quantification showed that under stress, resilient mice and susceptible mice used different behavioral strategies and had different activity patterns (but not TS)
at the DA end of NAc.
Neurologically, resilient mice had greater activity in the vicinity of the attacker, including at the beginning of
a counterattack.
Conversely, susceptible mice had greater activity
at the onset of attack deviation and flight.
In TS and NAc, the response of DAT::GCaMP6f is reversely modulated close to the attacker (Figure from Nature) The study also performed open-loop optical genetic stimulation of DA neurons projected by NAc during failure (random timing) or timed
specific behaviors using real-time behavioral classification.
Both open-loop activation and counter-attack time activation promote resilience and reorganize behavior in failure toward resilience-related patterns
.
In summary, the research work highlights the power of
combining complex, ethnologically relevant social stress paradigms with behavioral quantification, chronic and projection-specific neural recording, and behavior-specific neural manipulation tools.
This study elucidates the link between dopaminergic neural activity and behavior, advancing our understanding of
the role of neuromodulation in regulating individual differences in pathological outcomes.
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