Limits...
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.

Show MeSH

Related in: MedlinePlus

AMPARs and NMDARs must be colocalized to enhance the early phase of synaptic Ca influx.(A) Schematic of uncaging locations (far left): control is in black and “NMDAR-only” distant uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “NMDAR-only” (red) uncaging locations. (B) Schematic of uncaging locations (far left): control is in black and “AMPAR-only” dendritic uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “AMPAR-only” (red) uncaging locations. (C) Schematic of uncaging locations (far left): control is in black and the paired NMDAR-only and AMPAR-only uncaging locations are illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and paired NMDAR-only and AMPAR-only (red) uncaging locations. The linear sums of the responses obtained with NMDAR-only and AMPAR-only uncaging protocols shown in Panels (A) and (B) are indicated by the dashed lines.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2734993&req=5

pbio-1000190-g004: AMPARs and NMDARs must be colocalized to enhance the early phase of synaptic Ca influx.(A) Schematic of uncaging locations (far left): control is in black and “NMDAR-only” distant uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “NMDAR-only” (red) uncaging locations. (B) Schematic of uncaging locations (far left): control is in black and “AMPAR-only” dendritic uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “AMPAR-only” (red) uncaging locations. (C) Schematic of uncaging locations (far left): control is in black and the paired NMDAR-only and AMPAR-only uncaging locations are illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and paired NMDAR-only and AMPAR-only (red) uncaging locations. The linear sums of the responses obtained with NMDAR-only and AMPAR-only uncaging protocols shown in Panels (A) and (B) are indicated by the dashed lines.

Mentions: In order to understand if the graded modulation of synaptic Ca influx by AMPAR opening is made possible by the electrical properties of the spine neck, we examined if the opening of dendritic AMPARs located at the base of the spine is also able to enhance the rapid phase of iCa (Figure 4). For this analysis, each spine was stimulated with four different spatiotemporal patterns of glutamate uncaging designed to mimic (1) normal synaptic activation of AMPARs and NMDARs on the spine head, (2) activation of only NMDARs on the spine head, (3) activation of only AMPARs on the neighboring dendrite, and (4) near simultaneous activation of spine head NMDARs and dendritic AMPARs.


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

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

AMPARs and NMDARs must be colocalized to enhance the early phase of synaptic Ca influx.(A) Schematic of uncaging locations (far left): control is in black and “NMDAR-only” distant uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “NMDAR-only” (red) uncaging locations. (B) Schematic of uncaging locations (far left): control is in black and “AMPAR-only” dendritic uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “AMPAR-only” (red) uncaging locations. (C) Schematic of uncaging locations (far left): control is in black and the paired NMDAR-only and AMPAR-only uncaging locations are illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and paired NMDAR-only and AMPAR-only (red) uncaging locations. The linear sums of the responses obtained with NMDAR-only and AMPAR-only uncaging protocols shown in Panels (A) and (B) are indicated by the dashed lines.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-1000190-g004: AMPARs and NMDARs must be colocalized to enhance the early phase of synaptic Ca influx.(A) Schematic of uncaging locations (far left): control is in black and “NMDAR-only” distant uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “NMDAR-only” (red) uncaging locations. (B) Schematic of uncaging locations (far left): control is in black and “AMPAR-only” dendritic uncaging is illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and “AMPAR-only” (red) uncaging locations. (C) Schematic of uncaging locations (far left): control is in black and the paired NMDAR-only and AMPAR-only uncaging locations are illustrated in red. uEPSPs (left), Δ[Ca]spine (middle), and iCa (right) are shown for control (black) and paired NMDAR-only and AMPAR-only (red) uncaging locations. The linear sums of the responses obtained with NMDAR-only and AMPAR-only uncaging protocols shown in Panels (A) and (B) are indicated by the dashed lines.
Mentions: In order to understand if the graded modulation of synaptic Ca influx by AMPAR opening is made possible by the electrical properties of the spine neck, we examined if the opening of dendritic AMPARs located at the base of the spine is also able to enhance the rapid phase of iCa (Figure 4). For this analysis, each spine was stimulated with four different spatiotemporal patterns of glutamate uncaging designed to mimic (1) normal synaptic activation of AMPARs and NMDARs on the spine head, (2) activation of only NMDARs on the spine head, (3) activation of only AMPARs on the neighboring dendrite, and (4) near simultaneous activation of spine head NMDARs and dendritic AMPARs.

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