期刊
JOURNAL OF NEUROSCIENCE
卷 38, 期 40, 页码 8515-8525出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0569-18.2018
关键词
appetite; astrocytes; ATP; cholecystokinin; dorsomedial hypothalamus; GABA
资金
- Canadian Institutes for Health Research
- Natural Sciences and Engineering Research Council
- Alberta Innovates Health Solutions (AIHS)
- AIHS
- Hotchkiss Brain Institute Obesity Initiative Studentship
- Campus Alberta Neuroscience
Whether synapses in appetite-regulatory brain regions undergo long-term changes in strength in response to satiety peptides is poorly understood. Here we show that following bursts of afferent activity, the neuromodulator and satiety peptide cholecystokinin (CCK) shifts the plasticity of GABA synapses in the dorsomedial nucleus of the hypothalamus of male Sprague Dawley rats from long-term depression to long-term potentiation (LTP). This LTP requires the activation of both type 2 CCK receptors and group 5 metabotropic glutamate receptors, resulting in a rise in astrocytic intracellular calcium and subsequent ATP release. ATP then acts on presynaptic P2X receptors to trigger a prolonged increase in GABA release. Our observations demonstrate a novel form of CCK-mediated plasticity that requires astrocytic ATP release, and could serve as a mechanism for appetite regulation.
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