期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 44, 页码 19073-19078出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1009803107
关键词
synaptic transmission; glutamate; plasticity; endocannabinoids
资金
- Japan Society for the Promotion of Science [19390309]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- National Institutes of Health [MH083011, MH090464]
- United States Army Medical Research Acquisition Activity (USAMRAA) [W81XWH-08-2-0126]
- Whitehall Foundation
- Grants-in-Aid for Scientific Research [19390309] Funding Source: KAKEN
Synaptic rules that may determine the interaction between coexisting forms of long-term potentiation (LTP) at glutamatergic central synapses remain unknown. Here, we show that two mechanistically distinct forms of LTP could be induced in thalamic input to the lateral nucleus of the amygdala (LA) with an identical presynaptic stimulation protocol, depending on the level of postsynaptic membrane polarization. One form of LTP, resulting from pairing of postsynaptic depolarization and low-frequency presynaptic stimulation, was both induced and expressed postsynaptically (post-LTP). The same stimulation in the absence of postsynaptic depolarization led to LTP, which was induced and expressed presynaptically (pre-LTP). The inducibility of coexisting pre- and postsynaptic forms of LTP at synapses in thalamic input followed a well-defined hierarchical order, such that pre-LTP was suppressed when post-LTP was induced. This interaction was mediated by activation of cannabinoid type 1 receptors by endogenous cannabinoids released in the lateral nucleus of the amygdala in response to activation of the type 1 metabotropic glutamate receptor. These results suggest a previously unknown mechanism by which the hierarchy of coexisting forms of long-term synaptic plasticity in the neural circuits of learned fear could be established, possibly reflecting the hierarchy of memories for the previously experienced fearful events according to their aversiveness level.
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