学術雑誌論文

学術雑誌論文

Neuron. 2024, 112(17), p. 2955-2972.e9

Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs

Cell Press

英語

2024-09-01

https://doi.org/10.1016/j.neuron.2024.06.017

Nakanishi Y., Izumi M., Matsushita H., et al. Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs. Neuron 112, 2955 (2024); https://doi.org/10.1016/j.neuron.2024.06.017.

Regulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis. Using genome-wide approaches, we identify SEMA6D as a pleiotropic gene for both psychiatric and metabolic traits in human. Sema6d deficiency increases anxiety in mice. When fed a high-fat diet, Sema6d−/− mice display attenuated obesity and enhanced myelopoiesis compared with control mice due to higher sympathetic activity via the β3-adrenergic receptor. Genetic manipulation and spatial and single-nucleus transcriptomics reveal that SEMA6D in amygdalar interneurons is responsible for regulating anxiogenic and autonomic responses. Mechanistically, SEMA6D is required for synaptic maturation and γ-aminobutyric acid transmission. These results demonstrate that SEMA6D is important for the normal functioning of the neural circuits in the amygdala, coupling emotional, metabolic, and inflammatory responses.

This article is licensed under a Creative Commons Attribution 4.0 International License.

98345

Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs

Cell Press

英語

2024-09-01

Neuron

112

17

2955

2972.e9

https://doi.org/10.1016/j.neuron.2024.06.017

https://hdl.handle.net/11094/98345