Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites.
Increases in cytosolic Ca2+ concentration ([Ca2+]i) mediated by NMDA-sensitive glutamate receptors (NMDARs) are important for synaptic plasticity. We studied a wide variety of dendritic spines on rat CA1 pyramidal neurons in acute hippocampal slices. Two-photon uncaging and Ca2+ imaging revealed that NMDAR-mediated currents increased with spine-head volume and that even the smallest spines contained a significant number of NMDARs. The fate of Ca2+ that entered spine heads through NMDARs was governed by the shape (length and radius) of the spine neck. Larger spines had necks that permitted greater efflux of Ca2+ into the dendritic shaft, whereas smaller spines manifested a larger increase in [Ca2+]i within the spine compartment as a result of a smaller Ca2+ flux through the neck. Spine-neck geometry is thus an important determinant of spine Ca2+ signaling, allowing small spines to be the preferential sites for isolated induction of long-term potentiation.
Noguchi
Jun
J
Department of Cell Physiology, National Institute for Physiological Sciences and Graduate University of Advanced Studies (SOKENDAI), Myodaiji, Okazaki 444-8787, Japan.
Matsuzaki
Masanori
M
Ellis-Davies
Graham C R
GC
Kasai
Haruo
H
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D007834:Lasers; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
C440256:4-methoxy-7-nitroindolinyl-glutamate; D005971:Glutamates; D007211:Indoles; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D014633:Valine; D002118:Calcium