title: Backpropagating action potentials enable detection of extrasynaptic glutamate by NMDA receptors.
abstract: 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, back-propagating action potentials (bAPs) recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are "protected," under baseline conditions, from such glutamate influences by peri-synaptic transporters: we detect bAP-evoked Ca(2+) entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca(2+) entry either downregulates or upregulates an h-channel conductance (G(h)) 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 G(h) plasticity. G(h) 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.
authors: RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors: Yu-Wei
authors: YW
authors: Wu
authors: Sergei
authors: S
authors: Grebenyuk
authors: Thomas J
authors: TJ
authors: McHugh
authors: Dmitri A
authors: DA
authors: Rusakov
authors: Alexey
authors: A
authors: Semyanov
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002118:Calcium