Professor Tianming Gao reveals that the neural circuits that regulate anxiety and fear at the same time have very different functions

Click on the blue word to pay attention to our medial prefrontal cortex (mPFC) is the high-level brain area of ​​the brain that regulates emotions, cognition, decision-making and other functions
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mPFC integrates the output and input projected to the subcortical area to regulate anxiety and fear
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The inferior marginal area (IL) is an important sub-area of ​​the mPFC brain area, and a key upstream brain area in the emotional and emotional regulation circuit in the brain
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Rats showed anxiolytic phenotypes after damaging the IL area, and activating the brain area caused anxiety-like behaviors
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Although there are more and more studies on the molecular and circuit mechanisms of anxiety in the IL brain area, these are just the tip of the iceberg for the complex regulatory network of the brain
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On July 15, 2021, Professor Gao Tianming of Southern Medical University published an article in The Journal of Clinical Investigation, revealing that there are two neural circuits in the mPFC subregion, which play diametrically opposite roles in regulating anxiety and fear
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Light-regulated IL brain neurons cause anxiety behavior changes.
Researchers used light to activate excitatory neurons in the IL area, which obviously caused anxiety-like behaviors in mice.
After inhibiting this type of neurons, they showed anxiolytic behavioral phenotypes.
This is consistent with the results of previous studies
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In order to further find the brain area regulated by the top-down of the IL area, they injected an antegrade tracer virus into the brain area and found that axons projected to the thalamus, dorsal raphe nucleus, basolateral amygdala (BLA), and central amygdala (CeA).
), stria terminalis bed nucleus (,BNST), lateral septal nucleus (LS)
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So which of these downstream brain areas is specifically involved in anxiety? Do nothing, do nothing, the researchers activated the above-mentioned projection loops separately through optogenetic technology, and found that the activation of IL-LS loop caused anxiety-like behavior in mice, and showed anxiolytic behavioral phenotype after inhibiting the loop; Activating the IL-CeA loop exerts an anxiolytic behavioral effect, and inhibits the loop to cause anxiety-like behavior
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After injecting glutamate receptor antagonist into the brain area of ​​LS or CeA, the above-mentioned neural circuit loses its regulating effect on anxiety behavior
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Of course, researchers do not really regulate these neural circuits casually.
These brain areas are closely related to the occurrence of anxiety
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In addition, chronic restraint stress can cause anxiety-like behavior in mice, and activation of the IL-CeA loop can reverse the anxiety caused by this stress
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These results indicate that the IL-CeA loop and the IL-LS loop play completely opposite roles in the regulation of anxiety behavior
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Similar to anxiety, fear is also a negative emotion, which is also closely related to IL brain areas
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What role do these two loops play in fear? After the mice have undergone sound matching fear memory training, the IL-LS loop was light-activated during the dissipative training phase to enhance the expression of fear memory in mice, and the IL-CeA loop was activated to reduce the expression of fear memory
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On the contrary, the expression of fear memory is reduced during the training phase of chronically inhibiting IL-LS loop to dissipate, and the expression of fear memory is enhanced after inhibiting IL-CeA loop
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Things are far from that simple! CeA can be further subdivided into the lateral central amygdala (CeL) and the medial central amygdala (CeM).
These two subregions form a local microloop
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The CeA microloop regulation of anxiety behavior virus tracing experiment found that IL brain regions can project to CeL and CeM brain regions.
Light-activated IL-CeL induces anxiolytic behavioral effects in mice, and has no effect on the expression of fear memory behavior, but activates IL -CeM has no effect on anxious behavior, but reduces the expression of fear memory
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In summary, this article reveals that the IL brain area projects to different downstream brain areas (CeA and LS), and these two circuits play diametrically opposite roles in anxiety and fear memory
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Although there are differences in structure and function between the two loops, it does not mean that the two loops are completely isolated.
It may be a deep and shallow interaction
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[References] 1.
https://doi.
org/10.
1172/JCI145692 The pictures in the article are all from the references