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Click the blue word to follow us About 273 million people around the world suffer from anxiety disorders and are highly comorbid with depression
.
Studies have shown that the midbrain dopamine system plays a role in behavioral responses to acute and chronic stress: VTA (ventral tegmental area) → mPFC, VTA → NAc (nucleus accumbens) circuit dysfunction causes depression-like behavior
.
The basolateral amygdala (BLA) is a key brain region that regulates anxiety and receives projections from the VTA
.
On March 22, 2022, the research team of Han Minghu, a professor in the Department of Pharmacology of the Icahn School of Medicine at Mount Sinai and the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, revealed that the VTA → BLA loop encodes stress-related anxiety-like behaviors, but does not encode depression-like behaviors
.
The social frustration stress model is a widely used animal model to induce depression-like behaviors
.
When faced with stress, some mice appeared sensitive type, manifested as social disorder, anhedonia and other depressive-like behaviors, circadian rhythm disturbance, etc.
, and some showed resistant type, not depressive-like behavioral disorder
.
Interestingly, both resistant and sensitive mice had an anxiety-like behavioral phenotype (reduced dwell time in the central area in the open field test and reduced dwell time in the open arms of the elevated cross)
.
Figure 1: Stress-induced AD mice and A mice Based on the above characteristics, the researchers called the mice that exhibited both depression-like and anxiety-like behaviors as AD mice, and the stressed mice that only exhibited anxiety-like behaviors were called AD mice.
A mouse
.
VTA→NAc loop neuronal activity was enhanced in AD mice, but not in A mice
.
This suggests that different neural circuits may be involved in stress-induced depression-like and anxiety-like behaviors
.
The researchers found that the VTA→NAc and VTA→BLA loops had almost no overlap through virus tracing experiments.
Based on the increased activity of the VTA→NAc loop in AD mice, the VTA→BLA loop may be stress-induced depression-like and Differential circuits in anxiety-like behavior
.
Through in vitro experiments, it was found that the firing frequency and excitability of dopamine neurons in the VTA→BLA circuit of AD mice and A mice were reduced
.
Changes in this discharge activity were strongly associated with anxiety-like behaviors, but not depression-like behaviors
.
Figure 2: Fiber optic calcium imaging records VTA→BLA loop dopamine neuron activity.
It was further found by fiber optic calcium imaging that social behavior did not cause changes in VTA→BLA loop dopamine neuron activity
.
The longer the mice stayed in the open arm of the elevated plus maze prior to stress, the higher the activity of dopamine neurons in the VTA→BLA loop
.
However, after the stress, the mice stayed in the open arm for less time, and at the same time, the activity of dopamine neurons in the VTA→BLA circuit was weakened, which indicated that the VTA→BLA circuit was strongly associated with anxiety-like behaviors
.
Subthreshold acute stress (single challenge of mice for 5 minutes) did not induce anxiety-like behavior in mice, but after photoinhibition of the VTA → BLA circuit reduced the time that mice were in the elevated open arm and decreased in the open field.
Staying in the central area of the experiment did not affect the social behavior of the mice
.
Further experiments found that light activation of the VTA → BLA circuit could alleviate anxiety-like behaviors (increase the dwell time of the open arms) in AD mice and A mice, but could not alleviate behavioral disorders such as social impairment and anhedonia in AD mice
.
These results suggest that the VTA→BLA loop selectively encodes anxiety-like behaviors
.
Overall, this paper found that mice showed different responses to stress: some mice showed anxiety-like and depression-like behaviors, and some mice only showed anxiety-like behaviors, and the VTA→BLA circuit may be an important cause of this behavioral difference.
factor
.
[References] 1.
https://doi.
org/10.
1038/s41467-022-29155-1 The pictures in the text are from the references
.
Studies have shown that the midbrain dopamine system plays a role in behavioral responses to acute and chronic stress: VTA (ventral tegmental area) → mPFC, VTA → NAc (nucleus accumbens) circuit dysfunction causes depression-like behavior
.
The basolateral amygdala (BLA) is a key brain region that regulates anxiety and receives projections from the VTA
.
On March 22, 2022, the research team of Han Minghu, a professor in the Department of Pharmacology of the Icahn School of Medicine at Mount Sinai and the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, revealed that the VTA → BLA loop encodes stress-related anxiety-like behaviors, but does not encode depression-like behaviors
.
The social frustration stress model is a widely used animal model to induce depression-like behaviors
.
When faced with stress, some mice appeared sensitive type, manifested as social disorder, anhedonia and other depressive-like behaviors, circadian rhythm disturbance, etc.
, and some showed resistant type, not depressive-like behavioral disorder
.
Interestingly, both resistant and sensitive mice had an anxiety-like behavioral phenotype (reduced dwell time in the central area in the open field test and reduced dwell time in the open arms of the elevated cross)
.
Figure 1: Stress-induced AD mice and A mice Based on the above characteristics, the researchers called the mice that exhibited both depression-like and anxiety-like behaviors as AD mice, and the stressed mice that only exhibited anxiety-like behaviors were called AD mice.
A mouse
.
VTA→NAc loop neuronal activity was enhanced in AD mice, but not in A mice
.
This suggests that different neural circuits may be involved in stress-induced depression-like and anxiety-like behaviors
.
The researchers found that the VTA→NAc and VTA→BLA loops had almost no overlap through virus tracing experiments.
Based on the increased activity of the VTA→NAc loop in AD mice, the VTA→BLA loop may be stress-induced depression-like and Differential circuits in anxiety-like behavior
.
Through in vitro experiments, it was found that the firing frequency and excitability of dopamine neurons in the VTA→BLA circuit of AD mice and A mice were reduced
.
Changes in this discharge activity were strongly associated with anxiety-like behaviors, but not depression-like behaviors
.
Figure 2: Fiber optic calcium imaging records VTA→BLA loop dopamine neuron activity.
It was further found by fiber optic calcium imaging that social behavior did not cause changes in VTA→BLA loop dopamine neuron activity
.
The longer the mice stayed in the open arm of the elevated plus maze prior to stress, the higher the activity of dopamine neurons in the VTA→BLA loop
.
However, after the stress, the mice stayed in the open arm for less time, and at the same time, the activity of dopamine neurons in the VTA→BLA circuit was weakened, which indicated that the VTA→BLA circuit was strongly associated with anxiety-like behaviors
.
Subthreshold acute stress (single challenge of mice for 5 minutes) did not induce anxiety-like behavior in mice, but after photoinhibition of the VTA → BLA circuit reduced the time that mice were in the elevated open arm and decreased in the open field.
Staying in the central area of the experiment did not affect the social behavior of the mice
.
Further experiments found that light activation of the VTA → BLA circuit could alleviate anxiety-like behaviors (increase the dwell time of the open arms) in AD mice and A mice, but could not alleviate behavioral disorders such as social impairment and anhedonia in AD mice
.
These results suggest that the VTA→BLA loop selectively encodes anxiety-like behaviors
.
Overall, this paper found that mice showed different responses to stress: some mice showed anxiety-like and depression-like behaviors, and some mice only showed anxiety-like behaviors, and the VTA→BLA circuit may be an important cause of this behavioral difference.
factor
.
[References] 1.
https://doi.
org/10.
1038/s41467-022-29155-1 The pictures in the text are from the references
