Dataset Information

Dissecting a disynaptic central amygdala-parasubthalamic nucleus neural circuit that mediates cholecystokinin-induced eating suppression.

ABSTRACT:

Objective

Cholecystokinin (CCK) plays a critical role in regulating eating and metabolism. Previous studies have mapped a multi-synapse neural pathway from the vagus nerve to the central nucleus of the amygdala (CEA) that mediates the anorexigenic effect of CCK. However, the neural circuit downstream of the CEA is still unknown due to the complexity of the neurons in the CEA. Here we sought to determine this circuit using a novel approach.

Methods

It has been established that a specific population of CEA neurons, marked by protein kinase C-delta (PKC-δ), mediates the anorexigenic effect of CCK by inhibiting other CEA inhibitory neurons. Taking advantage of this circuit, we dissected the neural circuit using a unique approach based on the idea that neurons downstream of the CEA should be disinhibited by CEA^PKC-δ+ neurons while being activated by CCK. We also used optogenetic assisted electrophysiology circuit mapping and in vivo chemogenetic manipulation methods to determine the circuit structure and function.

Results

We found that neurons in the parasubthalamic nucleus (PSTh) are activated by the activation of CEA^PKC-δ+ neurons and by the peripheral administration of CCK. We demonstrated that CEA^PKC-δ+ neurons inhibit the PSTh-projecting CEA neurons; accordingly, the PSTh neurons can be disynaptically disinhibited or "activated" by CEA^PKC-δ+ neurons. Finally, we showed that chemogenetic silencing of the PSTh neurons effectively attenuates the eating suppression induced by CCK.

Conclusions

Our results identified a disynaptic CEA-PSTh neural circuit that mediates the anorexigenic effect of CCK and thus provide an important neural mechanism of how CCK suppresses eating.

SUBMITTER: Sanchez MR

PROVIDER: S-EPMC8844644 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Dissecting a disynaptic central amygdala-parasubthalamic nucleus neural circuit that mediates cholecystokinin-induced eating suppression.

Sanchez Marina Rodriguez MR Wang Yong Y Cho Tiffany S TS Schnapp Wesley I WI Schmit Matthew B MB Fang Caohui C Cai Haijiang H

Molecular metabolism 20220120

<h4>Objective</h4>Cholecystokinin (CCK) plays a critical role in regulating eating and metabolism. Previous studies have mapped a multi-synapse neural pathway from the vagus nerve to the central nucleus of the amygdala (CEA) that mediates the anorexigenic effect of CCK. However, the neural circuit downstream of the CEA is still unknown due to the complexity of the neurons in the CEA. Here we sought to determine this circuit using a novel approach.<h4>Methods</h4>It has been established that a sp ...[more]

PMID: 35066159

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Project description:As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+ circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENT Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+ pathway in a descending facilitatory mechanism underlying neuropathic pain.

Dataset Information

Dissecting a disynaptic central amygdala-parasubthalamic nucleus neural circuit that mediates cholecystokinin-induced eating suppression.

Objective

Methods

Results

Conclusions

Publications

Dissecting a disynaptic central amygdala-parasubthalamic nucleus neural circuit that mediates cholecystokinin-induced eating suppression.

Similar Datasets

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