Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress
Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress
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DOI：
10.1073/pnas.0905568107
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发表时间：
2010-02-02
影响因子：
11.1
通讯作者：
Winder, Danny G.
中科院分区：
文献类型：
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作者：
McElligott, Zoe A.;Klug, Jason R.;Winder, Danny G.
长期抑制（LTD）是一种重要的突触机制，限制了神经回路对认知和情绪行为的兴奋性影响。LTD诱导的一个主要途径是通过G(q)-连接受体的信号募集，这些受体被去甲肾上腺素（NE）、乙酰胆碱和谷氨酸激活。来自这些递质家族的受体被认为汇聚在一个共同的突触后LTD维持机制上，因此异突触和同突触诱导在谷氨酸突触功效方面产生类似的改变。我们报道，在终纹的背外侧和腹外侧床核（BNST）中，谷氨酸或NE募集G(q)-连接受体启动机制上不同形式的突触后维持LTD，这些LTDs受到应激暴露的不同调节。特别是，我们发现尽管mGluR5-和α(1)-肾上腺素能受体（AR）依赖的LTDs都涉及突触后内吞作用，但α (1)-AR启动的LTDs只涉及通过钙渗透性AMPA受体调节信号。此外，α (1)- ar -而不是mglur5依赖性LTD被约束应力破坏。长期暴露于乙醇的小鼠α (1)-AR LTD也受损。因此，这些数据表明，在BNST中，NE-和谷氨酸激活的G(q)连接信号通路在应激反应中调节谷氨酸突触的作用是不同的。
Long-term depression (LTD) is an important synaptic mechanism for limiting excitatory influence over circuits subserving cognitive and emotional behavior. A major means of LTD induction is through the recruitment of signaling via G(q)-linked receptors activated by norepinephrine (NE), acetylcholine, and glutamate. Receptors from these transmitter families have been proposed to converge on a common postsynaptic LTD maintenance mechanism, such that hetero- and homosynaptic induction produce similar alterations in glutamate synapse efficacy. We report that in the dorsolateral and ventrolateral bed nucleus of the stria terminalis (BNST), recruitment of G(q)-linked receptors by glutamate or NE initiates mechanistically distinct forms of postsynaptically maintained LTD and these LTDs are differentially regulated by stress exposure. In particular, we show that although both mGluR5- and alpha(1)-adrenergic receptor (AR)-dependent LTDs involve postsynaptic endocytosis, the alpha(1)-AR-initiated LTD exclusively involves modulation of signaling through calcium-permeable AMPA receptors. Further, alpha(1)-AR- but not mGluR5-dependent LTD is disrupted by restraint stress. alpha(1)-AR LTD is also impaired in mice chronically exposed to ethanol. These data thus suggest that in the BNST, NE- and glutamate-activated G(q)-linked signaling pathways differentially tune glutamate synapse efficacy in response to stress.