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Click on the blue word to focus on our midbrain dopaminergic system (VTA, nucleus accumbens NAc) neurons in the midbrain play a key role in motivated behavior
.
Corticotropin-releasing hormone (CRH) regulates stress-related behavioral responses through CRH receptor 1 (CRHR1) expressed in dopamine neurons on the VTA
.
In addition, knockout of CRHR1 in dopamine neurons in the VTA brain region promotes anxiety-like behavior, and knockout of CRHR1 in inhibitory neurons in this region can exert anxiolytic effects
.
On March 23, 2022, the research team of Carmen Sandi of EPFL revealed the mechanism of the difference of goal-motivated behavior in different anxiety levels under stress state
.
Figure 1: Motivational behavior of low- and high-anxiety rats after stress The researchers defined high-anxiety rats according to the time spent in the open arms of the elevated plus maze (the ratio of open arms to total time was less than 5%) and low-anxiety rats (ratio of open arm dwell time to total time greater than 20%)
.
The high-anxiety and low-anxiety rats were then placed on a 95-cm-high platform.
After receiving this acute stress, the low-anxiety rats exhibited stronger motivational behaviors, more correct nose touches, and higher rewards.
In contrast, the motivational behavior of high-anxiety rats decreased, and the number of correct nose touches decreased (Figure 1)
.
Figure 2: Expression of CRHR1 on dopamine neurons in the VTA brain region.
Immunoin situ hybridization experiments found that the expression of CRHR1 in dopamine neurons in the VTA brain region of high-anxiety rats was lower than that of low-anxiety rats, but CRHR1 was on inhibitory neurons in this region.
expression did not differ
.
Injection of CRH through specific VTA brain regions can increase the target motivational behavior of low-anxiety rats and inhibit the motivational behavior of high-anxiety mice, which can simulate the effect of acute stress
.
Under normal conditions, there is almost no difference in the firing activity of dopamine neurons in the VTA area of low-anxiety and high-anxiety rats.
There was little effect on dopaminergic activity in mice
.
The above results indicated that the effects of CRH on the activity of dopamine neurons in low-anxiety rats and high-anxiety rats were different
.
Previous studies have shown that CRHR1 expressed by neurons in the VTA brain region can promote the release of the inhibitory transmitter GABA to dopamine neurons
.
However, after blocking inhibitory transmission, the difference in neuronal activity of CRH in low-anxiety and high-anxiety rats persisted
.
Interestingly, however, the above-mentioned differences in the activity of CRH on dopamine neurons did not exist after knockdown of CRHR1
.
Figure 3: Overexpression of CRHR1 enhances motivational behaviors in high-anxiety rats.
Acute stress does not increase target-motivated behaviors in low-anxiety rats after reducing CRHR1 in the VTA brain region.
In vitro incubation of CRH does not enhance dopamine in low-anxiety rats.
Neuronal firing activity
.
Increasing the expression of CRHR1 by a viral strategy can increase the motivational behavior of high-anxiety rats under acute stress
.
This further indicated that the differential expression of CRHR1 in the VTA brain regions of low-anxiety and high-anxiety rats caused the differential responses of dopamine neurons to CRH
.
Overall, this paper revealed the differential effects of acute stress on the target motivational behavior of rats with different anxiety levels: promoting the motivational behavior of low-anxiety rats and reducing the motivational behavior of high-anxiety rats.
This difference is caused by Caused by the differential expression of CRHR1 in dopamine neurons in the VTA brain region
.
[Reference] 1.
Zalachoras et al.
, Sci.
Adv.
8, eabj9019 (2022) , Opposite effects of stress on effortful motivation in high and low anxiety are mediated by CRHR1 in the VTA The pictures in the text are from the reference
.
Corticotropin-releasing hormone (CRH) regulates stress-related behavioral responses through CRH receptor 1 (CRHR1) expressed in dopamine neurons on the VTA
.
In addition, knockout of CRHR1 in dopamine neurons in the VTA brain region promotes anxiety-like behavior, and knockout of CRHR1 in inhibitory neurons in this region can exert anxiolytic effects
.
On March 23, 2022, the research team of Carmen Sandi of EPFL revealed the mechanism of the difference of goal-motivated behavior in different anxiety levels under stress state
.
Figure 1: Motivational behavior of low- and high-anxiety rats after stress The researchers defined high-anxiety rats according to the time spent in the open arms of the elevated plus maze (the ratio of open arms to total time was less than 5%) and low-anxiety rats (ratio of open arm dwell time to total time greater than 20%)
.
The high-anxiety and low-anxiety rats were then placed on a 95-cm-high platform.
After receiving this acute stress, the low-anxiety rats exhibited stronger motivational behaviors, more correct nose touches, and higher rewards.
In contrast, the motivational behavior of high-anxiety rats decreased, and the number of correct nose touches decreased (Figure 1)
.
Figure 2: Expression of CRHR1 on dopamine neurons in the VTA brain region.
Immunoin situ hybridization experiments found that the expression of CRHR1 in dopamine neurons in the VTA brain region of high-anxiety rats was lower than that of low-anxiety rats, but CRHR1 was on inhibitory neurons in this region.
expression did not differ
.
Injection of CRH through specific VTA brain regions can increase the target motivational behavior of low-anxiety rats and inhibit the motivational behavior of high-anxiety mice, which can simulate the effect of acute stress
.
Under normal conditions, there is almost no difference in the firing activity of dopamine neurons in the VTA area of low-anxiety and high-anxiety rats.
There was little effect on dopaminergic activity in mice
.
The above results indicated that the effects of CRH on the activity of dopamine neurons in low-anxiety rats and high-anxiety rats were different
.
Previous studies have shown that CRHR1 expressed by neurons in the VTA brain region can promote the release of the inhibitory transmitter GABA to dopamine neurons
.
However, after blocking inhibitory transmission, the difference in neuronal activity of CRH in low-anxiety and high-anxiety rats persisted
.
Interestingly, however, the above-mentioned differences in the activity of CRH on dopamine neurons did not exist after knockdown of CRHR1
.
Figure 3: Overexpression of CRHR1 enhances motivational behaviors in high-anxiety rats.
Acute stress does not increase target-motivated behaviors in low-anxiety rats after reducing CRHR1 in the VTA brain region.
In vitro incubation of CRH does not enhance dopamine in low-anxiety rats.
Neuronal firing activity
.
Increasing the expression of CRHR1 by a viral strategy can increase the motivational behavior of high-anxiety rats under acute stress
.
This further indicated that the differential expression of CRHR1 in the VTA brain regions of low-anxiety and high-anxiety rats caused the differential responses of dopamine neurons to CRH
.
Overall, this paper revealed the differential effects of acute stress on the target motivational behavior of rats with different anxiety levels: promoting the motivational behavior of low-anxiety rats and reducing the motivational behavior of high-anxiety rats.
This difference is caused by Caused by the differential expression of CRHR1 in dopamine neurons in the VTA brain region
.
[Reference] 1.
Zalachoras et al.
, Sci.
Adv.
8, eabj9019 (2022) , Opposite effects of stress on effortful motivation in high and low anxiety are mediated by CRHR1 in the VTA The pictures in the text are from the reference
