Adrenergic Gate Release for Spike Timing-Dependent Synaptic Potentiation

作者：Liu Yanling; Cui Lei; Schwarz Martin K; Dong Yan; Schlueter Oliver M

来源：Neuron, 2017, 93(2): 394-408.

DOI：10.1016/j.neuron.2016.12.039

• Kv1.1
• SAP97
• dendritic excitability
• hippocampus
• signaling scaffold
• spike timing-dependent plasticity
• β-adrenoceptor

Spike timing-dependent synaptic plasticity (STDP) serves as a key cellular correlate of associative learning, which is facilitated by elevated attentional and emotional states involving activation of adrenergic signaling. At cellular levels, adrenergic signaling increases dendrite excitability, but the underlying mechanisms remain elusive. Here we show that activation of beta 2-adrenoceptors promoted STD long-term synaptic potentiation at mouse hippocampal excitatory synapses by inactivating dendritic Kv1.1-containing potassium channels, which increased dendrite excitability and facilitated dendritic propagation of postsynaptic depolarization, potentially improving coincidental activation of pre- and postsynaptic terminals. We further demonstrate that adrenergic modulation of Kv1.1 was mediated by the signaling scaffold SAP97, which, through direct protein-protein interactions, escorts beta 2 signaling to remove Kv1.1 from the dendrite surface. These results reveal a mechanism through which the postsynaptic signaling scaffolds bridge the aroused brain state to promote induction of synaptic plasticity and potentially to enhance spike timing and memory encoding.

• 出版日期2017-1-18