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Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines.

Bloodgood BL, Giessel AJ, Sabatini BL - PLoS Biol. (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America.

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.

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Synaptic, but not dendritic, depolarization activates VGCCs in the spine head.(A) uEPSPs recorded at the soma (left), Ca-dependent changes in fluorescence measured in the spine head (middle), and Ca-dependent changes in fluorescence measured in the dendrite (right) generated in response to uncaging at the spine (top) or dendrite (bottom). Data are shown as the mean (line)±SEM (shaded region). (B) Summary of amplitudes of uEPSPs (left), Δ[Ca]spine (middle), and Δ[Ca]den (right) evoked by spine or dendrite stimulation measured in control conditions (black) and in the presence of a cocktail of VGCC antagonists (grey). * indicates that the difference seen comparing spine stimulation versus dendrite stimulation is significant, whereas # indicates a significant difference comparing across control and VGCC cocktail conditions.
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pbio-1000190-g002: Synaptic, but not dendritic, depolarization activates VGCCs in the spine head.(A) uEPSPs recorded at the soma (left), Ca-dependent changes in fluorescence measured in the spine head (middle), and Ca-dependent changes in fluorescence measured in the dendrite (right) generated in response to uncaging at the spine (top) or dendrite (bottom). Data are shown as the mean (line)±SEM (shaded region). (B) Summary of amplitudes of uEPSPs (left), Δ[Ca]spine (middle), and Δ[Ca]den (right) evoked by spine or dendrite stimulation measured in control conditions (black) and in the presence of a cocktail of VGCC antagonists (grey). * indicates that the difference seen comparing spine stimulation versus dendrite stimulation is significant, whereas # indicates a significant difference comparing across control and VGCC cocktail conditions.

Mentions: On average, dendrite and spine stimulation evoked equal amplitude uEPSPs as measured at the soma (0.99±0.05 mV, n = 15, and 0.91±0.07 mV, n = 10, respectively), whereas spine stimulation evoked ∼5-fold larger Δ[Ca]spine than dendritic stimulation (ΔG/Gsat: 15.7%±2.9% and 3.3%±2.1%, respectively) (Figure 2B). Both stimuli produced only small Δ[Ca]den (ΔG/Gsat: 0.9%±0.3% and 3.9%±0.8% for stimulation of the spine and dendrite, respectively) (Figure 2B). Thus, dendritic stimulation is unable to activate voltage-gated Ca sources located in the spine head.


Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines.

Bloodgood BL, Giessel AJ, Sabatini BL - PLoS Biol. (2009)

Synaptic, but not dendritic, depolarization activates VGCCs in the spine head.(A) uEPSPs recorded at the soma (left), Ca-dependent changes in fluorescence measured in the spine head (middle), and Ca-dependent changes in fluorescence measured in the dendrite (right) generated in response to uncaging at the spine (top) or dendrite (bottom). Data are shown as the mean (line)±SEM (shaded region). (B) Summary of amplitudes of uEPSPs (left), Δ[Ca]spine (middle), and Δ[Ca]den (right) evoked by spine or dendrite stimulation measured in control conditions (black) and in the presence of a cocktail of VGCC antagonists (grey). * indicates that the difference seen comparing spine stimulation versus dendrite stimulation is significant, whereas # indicates a significant difference comparing across control and VGCC cocktail conditions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2734993&req=5

pbio-1000190-g002: Synaptic, but not dendritic, depolarization activates VGCCs in the spine head.(A) uEPSPs recorded at the soma (left), Ca-dependent changes in fluorescence measured in the spine head (middle), and Ca-dependent changes in fluorescence measured in the dendrite (right) generated in response to uncaging at the spine (top) or dendrite (bottom). Data are shown as the mean (line)±SEM (shaded region). (B) Summary of amplitudes of uEPSPs (left), Δ[Ca]spine (middle), and Δ[Ca]den (right) evoked by spine or dendrite stimulation measured in control conditions (black) and in the presence of a cocktail of VGCC antagonists (grey). * indicates that the difference seen comparing spine stimulation versus dendrite stimulation is significant, whereas # indicates a significant difference comparing across control and VGCC cocktail conditions.
Mentions: On average, dendrite and spine stimulation evoked equal amplitude uEPSPs as measured at the soma (0.99±0.05 mV, n = 15, and 0.91±0.07 mV, n = 10, respectively), whereas spine stimulation evoked ∼5-fold larger Δ[Ca]spine than dendritic stimulation (ΔG/Gsat: 15.7%±2.9% and 3.3%±2.1%, respectively) (Figure 2B). Both stimuli produced only small Δ[Ca]den (ΔG/Gsat: 0.9%±0.3% and 3.9%±0.8% for stimulation of the spine and dendrite, respectively) (Figure 2B). Thus, dendritic stimulation is unable to activate voltage-gated Ca sources located in the spine head.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America.

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.

Show MeSH
Related in: MedlinePlus