title: Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines.
abstract: Excitatory synapses on mammalian principal neurons are typically formed onto dendritic spines, which consist of a bulbous head separated from the parent dendrite by a thin neck. Although activation of voltage-gated channels in the spine and stimulus-evoked constriction of the spine neck can influence synaptic signals, the contribution of electrical filtering by the spine neck to basal synaptic transmission is largely unknown. Here we use spine and dendrite calcium (Ca) imaging combined with 2-photon laser photolysis of caged glutamate to assess the impact of electrical filtering imposed by the spine morphology on synaptic Ca transients. We find that in apical spines of CA1 hippocampal neurons, the spine neck creates a barrier to the propagation of current, which causes a voltage drop and results in spatially inhomogeneous activation of voltage-gated Ca channels (VGCCs) on a micron length scale. Furthermore, AMPA and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively) that are colocalized on individual spine heads interact to produce two kinetically and mechanistically distinct phases of synaptically evoked Ca influx. Rapid depolarization of the spine triggers a brief and large Ca current whose amplitude is regulated in a graded manner by the number of open AMPARs and whose duration is terminated by the opening of small conductance Ca-activated potassium (SK) channels. A slower phase of Ca influx is independent of AMPAR opening and is determined by the number of open NMDARs and the post-stimulus potential in the spine. Biphasic synaptic Ca influx only occurs when AMPARs and NMDARs are coactive within an individual spine. These results demonstrate that the morphology of dendritic spines endows associated synapses with specialized modes of signaling and permits the graded and independent control of multiple phases of synaptic Ca influx.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Bloodgood
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Giessel
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D054351:Electrical Synapses / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D051379:Mice; D009431:Neural Conduction; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D055366:Synaptic Potentials; D009435:Synaptic Transmission
chemical_list: D015220:Calcium Channels; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid