Adrenergic Gate Release for Spike Timing-Dependent Synaptic Potentiation

• Published in: Neuron (Cambridge, Mass.) Mass.), 2017-01, Vol.93 (2), p.394-408
• Main Authors: Liu, Yanling, Cui, Lei, Schwarz, Martin K., Dong, Yan, Schlüter, Oliver M.
• Format: Article
• Language: English
• Subjects: Animals; Dendrites - metabolism; dendritic excitability; Discs Large Homolog 1 Protein; Guanylate Kinases - genetics; hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Immunohistochemistry; Kv1.1; Kv1.1 Potassium Channel - metabolism; Long-Term Potentiation - genetics; Membrane Proteins - genetics; Mice; Mice, Knockout; Microscopy, Confocal; Neural Inhibition; Neurons; Neurons - cytology; Neurons - metabolism; Optogenetics; Patch-Clamp Techniques; Potassium; Propagation; Receptors, Adrenergic, beta-2 - metabolism; Rodents; SAP97; signaling scaffold; spike timing-dependent plasticity; Statistical analysis; Synaptic Potentials; Transgenic animals; β-adrenoceptor
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2016.12.039

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 β2-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 β2 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. •Kv1.1 mediates dendritic potassium current in hippocampal neurons•Kv1.1 gates spike timing-dependent LTP at hippocampal synapses•SAP97 enables β2-adrenoceptor-induced inhibition of dendritic Kv1.1•SAP97/β2/Kv1.1-mediated regulation of dendrite excitability gates LTP Liu et al. report a molecular mechanism through which adrenergic signaling increases dendritic excitability to facilitate LTP induction, a finding explaining how attentional or emotional arousal facilitates learning.