Neuron: Dr. Yang Ben and others reveal the neurological mechanisms of fear-suppressing diet, providing a new target for pathological anorexia

It is well known that stress affects diet.
stress-promoting diet may be related to the brain's reward mechanism, the dopamine system.
little is known about the mechanisms by which stress inhibits diet.
20, 2021, D.James Surmeier's team published a research paper in the cell sub-journal Neuron entitled: Locus coeruleus anchors a trisynaptic circuit controling fear-induced suppression of feeding.
the paper sheds light on the neurological mechanisms of the locus coeruleus (LC) neurons that induce fear to suppress diet by studying the effects of fear on diet, one of the stressors.
D. James Surmeier is the paper's correspondent and Dr. Ben Yang is the first author and co-author.
three brain regions have been reported to be associated with fear and diet.
three brain regions are the central nucleus of amygdala, CeA, parabrachial nucleus, PBN, and the blue-spot nucleus (locus coeruleus, LC).
, for example, has been shown in multiple species that the removal of the central amygdala can eliminate fear responses.
harmful stimuli, such as fear, to the brain center, and activating the armside nucleus can also inhibit diet.
blue-spotted nucleus is the brain's epinephrine center, and the release of dethyroids causes the brain to arouse, and fear, diet are related.
how these three brain regions are linked, and whether they are related to fear-induced dietary suppression is unknown.
questions, the researchers conducted a "condition fear" experiment in mice.
found that the "condition fear" experiment itself did not affect the diet, but the re-emergence of fear memory can persist in suppressing the diet.
to further study its mechanisms, the researchers combined electrophysiology, photogenetics, chemical genetics, cross-genetics and other methods to reveal the neurological mechanisms of fear-suppressing diet.
first used electrophysiological methods to find that blue-spotted nucleine neurons may release dethyrene and glutamate together.
to confirm the findings, the researchers further used cross-genetic methods to confirm that blue spot nucleine neurons co-expression of luminine hydroxylase (a common label for blue spot nucleotide neurons) and type 2 vesicular glutamate transporter protein (vesicular gluta transporter 2, vGluT2) meet the conditions for co-release of dethyroline and glutamate.
, photogenetic methods confirm that blue-spotted nucleine neurons do release dethyroidine and glutamate.
further research has also revealed new neural path paths that the blue-spotted nucleus is projected into the arm's side core.
Chemical genetics activates blue-spotted nuclein neurons to suppress diet, suggesting that fear may activate arm-side neurons by activating blue-spotted nuclei neurons, causing a total release of neurotransmitter.
after clearing the path from the blue-spotted nucleus to the arm-side core, the researchers set their sights on the projection of the central amygdala to the blue-spotted nucleus.
previous studies suggested that central amygdala neurons are projected directly into the blue-spotted nuclei, activating blue-spotted nuclei neurons by releasing hormones that promote the release of adrenal corticosteroids.
But the researchers combined electrophysiological and photogenetic methods to find that the central amygdala is not projected directly to the blue-spotted nuclei, but to the arm niche, which inhibits the arm-side neurons by releasing γ-amino butyric acid.
"condition fear" inhibits the projection of the central amygdala to the armside nuclei.
further studies have found that the inhibitory mechanism is endotopic cannabinin-induced long-term inhibition.
synapses may be related to the persistent suppression of fear memories on diet.
synthesis of endogenetic cannabinin is generally guided by excitable synaptic inputs, but the projection from the central amygdala to the arm side core is inhibitory, suggesting that the long-term inhibition may be heterogenetic synaptic plasticity.
the above study showed that the blue spot core has excited neurotransmitter co-release, suggesting that projection from the blue spot nucleus may be the cause of the long-term inhibition of the heterogeneity synapse.
through a series of pharmacological and synaptic physiological experiments, the researchers finally confirmed that the neurotransmitter co-release of the blue-spotted nuclei did lead to long-term inhibition induced by endogenous cannabinin projected from the central amygdala to the arm-side nuclei.
Not only that, but neurotransmitter co-release of the blue-spotted nuclei is critical to the persistence and firmness of the long-term inhibition of the central amygdala to the arm-side nuclear projection, thus revealing for the first time the physiological function of the neurotransmitter co-release.
, inhibiting the co-release or suppression of endogenetic cannabinin pathlines of the neurotransmitters of the blue-spotted nucleus can block dietary inhibition caused by "conditional fear".
"condition fear" is a classic animal model of post-traumatic stress disorder, so clinically, the study provides a potential new target for dietary suppression caused by post-traumatic stress disorder.
, the study first reported the co-release of epinephrine and glutamate from blue-spotted nucleine neurons, challenging not only Dale's law in neuroscience, a neuron that releases a neurotransmitter, but also reveals the physiological function and biological logic of neurotransmitter co-release.
, as a normal physiological function, instantaneously suppresses other physiological needs such as diet, which is essential for species survival.
but in pathological conditions, such as post-traumatic stress disorder, fear can lead to long-term suppression of the diet.
the study not only revealed the mechanisms of fear-suppressing diet, but also provided new targets for the treatment of dietary suppression and pathological anorexia caused by post-traumatic stress disorder.