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1.
Mol Psychiatry ; 27(12): 4881-4892, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36117214

RESUMO

Exaggerated startle has been recognized as a core hyperarousal symptom of multiple fear-related anxiety disorders, such as post-traumatic stress disorder (PTSD) and panic disorder. However, the mechanisms driving this symptom are poorly understood. Here we reveal a neural projection from dorsal raphe nucleus (DRN) to a startle-controlling center reticulotegmental nucleus (RtTg) that mediates enhanced startle response under fear condition. Within RtTg, we identify an inhibitory microcircuit comprising GABAergic neurons in pericentral RtTg (RtTgP) and glutamatergic neurons in central RtTg (RtTgC). Inhibition of this RtTgP-RtTgC microcircuit leads to elevated startle amplitudes. Furthermore, we demonstrate that the conditioned fear-activated DRN 5-HTergic neurons send inhibitory projections to RtTgP GABAergic neurons, which in turn upregulate neuronal activities of RtTgC glutamatergic neurons. Chemogenetic activation of the DRN-RtTgP projections mimics the increased startle response under fear emotions. Moreover, conditional deletion of 5-HT1B receptor from RtTgP GABAergic neurons largely reverses the exaggeration of startle during conditioned fear. Thus, our study establishes the disinhibitory DRN-RtTgP-RtTgC circuit as a critical mechanism underlying exaggerated startle under fear emotions, and provides 5-HT1B receptor as a potential therapeutic target for treating hyperarousal symptom in fear-associated psychiatric disorders.


Assuntos
Medo , Receptor 5-HT1B de Serotonina , Núcleo Dorsal da Rafe , Medo/fisiologia , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Mesencéfalo/metabolismo , Mesencéfalo/fisiologia , Receptor 5-HT1B de Serotonina/genética , Receptor 5-HT1B de Serotonina/metabolismo , Reflexo de Sobressalto/fisiologia , Animais , Camundongos
2.
Opt Lett ; 47(18): 4750-4753, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36107081

RESUMO

We propose a microwave photonic temperature interrogation system with high resolution and sensitivity based on temperature-to-time mapping with a simple structure. In this work, a bidirectional chirped optical signal is constructed, and the temperature information is mapped to the time interval change of the output pulses by filtering the bidirectional chirped optical signal using the transmission spectrum of a Fabry-Perot filter. Only a low-speed oscilloscope is required to extract the time interval of the output pulses in the proposed scheme, and complex data processing as well as synchronizing processes are avoided. In a proof-of-concept experiment, a high temperature interrogation sensitivity of 18.24 µs/°C and a high resolution of 0.035°C are realized, demonstrating good potential for practical applications.

3.
Cell Metab ; 35(11): 2011-2027.e7, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37794596

RESUMO

Overeating disorders (ODs), usually stemming from dieting history and stress, remain a pervasive issue in contemporary society, with the pathological mechanisms largely unresolved. Here, we show that alterations in intestinal microbiota are responsible for the excessive intake of palatable foods in OD mice and patients with bulimia nervosa (BN). Stress combined with a history of dieting causes significant changes in the microbiota and the intestinal metabolism, which disinhibit the vagus nerve terminals in the gut and thereby lead to a subsequent hyperactivation of the gut-brain axis passing through the vagus, the solitary tract nucleus, and the paraventricular nucleus of the thalamus. The transplantation of a probiotic Faecalibacterium prausnitzii or dietary supplement of key metabolites restores the activity of the gut-to-brain pathway and thereby alleviates the OD symptoms. Thus, our study delineates how the microbiota-gut-brain axis mediates energy balance, unveils the underlying pathogenesis of the OD, and provides potential therapeutic strategies.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Animais , Camundongos , Eixo Encéfalo-Intestino , Microbioma Gastrointestinal/fisiologia , Encéfalo/metabolismo , Hiperfagia/metabolismo
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