Retrograde Opioid Signaling Regulates Glutamatergic Transmission in the Hypothalamus
Retrograde Opioid Signaling Regulates Glutamatergic Transmission in the Hypothalamus
复制标题
DOI：
10.1523/jneurosci.0381-09.2009
复制
发表时间：
2009-06-03
影响因子：
5.3
通讯作者：
Bains, Jaideep S.
中科院分区：
文献类型：
--
作者：
Iremonger, Karl J.;Bains, Jaideep S.
中枢神经系统中的阿片信号对于控制细胞兴奋性至关重要，然而内源性阿片肽释放的条件以及它们影响突触传递的确切机制仍然知之甚少。阿片肽dynorphin存在于下丘脑抗利尿激素神经元的胞体和树突中，并在体内动态控制这些细胞的兴奋性。在这里，我们发现动态啡在突触后活动的反应中从树突囊泡释放，并以逆行方式抑制兴奋性突触传递。这种抑制需要kappa-阿片受体的激活，其结果是突触前谷氨酸囊泡释放的减少。阿片抑制是Ca2+进入的下游，可能是由突触前融合机制的直接调节介导的。这些发现表明，神经元可能通过树突释放阿片来自我调节其兴奋性，从而抑制兴奋性突触传递。
Opioid signaling in the CNS is critical for controlling cellular excitability, yet the conditions under which endogenous opioid peptides are released and the precise mechanisms by which they affect synaptic transmission remain poorly understood. The opioid peptide dynorphin is present in the soma and dendrites of vasopressin neurons in the hypothalamus and dynamically controls the excitability of these cells in vivo. Here, we show that dynorphin is released from dendritic vesicles in response to postsynaptic activity and acts in a retrograde manner to inhibit excitatory synaptic transmission. This inhibition, which requires the activation of kappa-opioid receptors, results from a reduction in presynaptic release of glutamate vesicles. The opioid inhibition is downstream of Ca2+ entry and is likely mediated by a direct modulation of presynaptic fusion machinery. These findings demonstrate that neurons may self-regulate their excitability through the dendritic release of opioids to inhibit excitatory synaptic transmission.