Cell Reports
Volume 1, Issue 5, 31 May 2012, Pages 495-505
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Article
Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors

https://doi.org/10.1016/j.celrep.2012.03.007Get rights and content
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Summary

Synaptic NMDA receptors (NMDARs) are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs) recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh) of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.

Highlights

► Dendritic shaft NMDA receptors are bound to extrasynaptic glutamate ► Both dendritic shaft and spine NMDA receptors detect synaptic glutamate spillover ► Backpropagating APs help to detect both spillover and ambient glutamate ► Dendritic shaft NMDA receptors induce downregulation of h-channel conductance (Gh)

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