期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 16, 页码 6380-6385出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0601267103
关键词
cAMP; G protein; metabotropic glutamate receptors; long-term depression; long-term potentiation
资金
- NINDS NIH HHS [R01 NS044421, R01-NS44421] Funding Source: Medline
- OMHHE CDC HHS [MN50733] Funding Source: Medline
Presynaptic inhibitory G protein-coupled receptors play a critical role in regulating transmission at a number of synapses in the central and peripheral nervous system. We generated transgenic mice that express a constitutively active form of an inhibitory Ga subunit to examine the molecular mechanisms underlying the actions of one such receptor, metabotropic glutamate receptor (mGluR) 2, at mossy fiber-CA3 synapses in the hippocampus. mGluR2 participates in at least three types of mossy fiber synaptic plasticity, (i) transient suppression of synaptic transmission, (it) long-term depression (LTD), and (iii) inhibition of long-term potentiation (LTP), and we find that inhibitory Ga signaling is sufficient to account for the actions of mGluR2 in each. The fact that constitutively active G alpha(i2) occludes the transient suppression of synaptic transmission by mGluR2, while enhancing LTD, suggests further that these two forms of plasticity are expressed via different mechanisms. In addition, the LTP deficit observed in constitutively active G alpha(i2)-expressing mice suggests that mGluR2 activation may serve as a metaplastic switch to permit the induction of LTD by inhibiting LTP.
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