Dendritic Spines as Tunable Regulators of Synaptic Signals

Abstract

Neurons are perpetually receiving vast amounts of information in the form of synaptic input from surrounding cells. The majority of input occurs at thousands of dendritic spines, which mediate excitatory synaptic transmission in the brain, and is integrated by the dendritic and somatic compartments of the postsynaptic neuron. The functional role of dendritic spines in shaping biochemical and electrical signals transmitted via synapses has long been intensely studied. Yet, many basic questions remain unanswered, in particular regarding the impact of their nanoscale morphology on electrical signals. Here, we review our current understanding of the structure and function relationship of dendritic spines, focusing on the controversy of electrical compartmentalization and the potential role of spine structural changes in synaptic plasticity.

Keywords: dendritic spines; hippocampus; super-resolution fluorescence microscopy; synapses; synaptic plasticity.

Figure 1

Dendritic spine morphology. (A) STED image of basal dendrites on live CA1 pyramidal cells in organotypic hippocampal slice prepared from Thy1-YFP transgenic animals. The image is a maximum intensity projection over 10 μm and is subjected to a 1-pixel median filter. Scale bar is 10 μm. (B) Two rotated views of a surface rendered 3D STED image of live spines on a dendritic segment in organotypic hippocampal slice as above. The rendering was prepared using an ImageJ 3D viewer plugin (17). The scale bar is 1 μm. Images acquired as in Ref. (18), with the addition of 3D STED (19).

Figure 2

Biochemical compartmentalization of dendritic spines. Spine morphology defines the spine as a biochemical compartment. (A) Neighboring spines often differ widely in shape and size and, hence, compartmentalize diffusive signals in a very different way. The lines through the spines show where FRAP was recorded by line scanning. The FRAP traces and their diffusional time constants (τ) correspond to the individual spines according to the color code and sequence (top to bottom). Spines with thin, long necks and large heads experience slower diffusional recovery and, hence, higher τ values. Modified from Ref. (18). (B) Induction of LTP by glutamate uncaging triggers structural changes in spine heads and necks, which have opposite effects on compartmentalization, so that τ changes less than predicted by looking at either neck or head dynamics alone [modified from Ref. (18)]. Scale bars are 0.5 μm.

Figure 3

Are spines capable of compartmentalizing electrical signals? There is no consensus on the role of the spine neck in electrical signaling, and conflicting results have been reported. (A) A recent two-photon microscopy study comparing spine morphology with uncaging (u)EPSP amplitude did not see a correlation between somatic uEPSPs and neck length. The solid dots represent spontaneous synaptic activity (evaluated by calcium imaging). Reprinted from Bywalez et al. (74), with permission from Elsevier. (B) Using a similar experimental approach, a previous study reported a strong correlation between the same parameters. The discrepancy between the two studies adds to an ongoing controversy about the importance of the spine neck in electrical compartmentalization of synapses. Modified with permission from Ref. (69) Copyright (2006) National Academy of Sciences, USA.

Figure 4

Electrical compartmentalization of dendritic spines. (A) In the spine electrical circuit diagram, a variable current enters through the synaptic receptors, scaling with their conductance, g_syn, and with the electrical driving force, which is the difference between resting membrane potential and the reversal potential of the conductance, E_syn. The membrane resistance is so high that current will not escape, and it will instead pass first the neck resistance, R_neck, and then the dendritic input resistance, R_dendrite, on the way to the soma. The EPSP that the synaptic current generates along the way is defined by Ohm’s law and follows voltage divider law. (B) As the synaptic current scales with driving force, the depolarizing EPSPs produced by the current will have a self-dampening effect as they approach the glutamate receptor reversal potential, E_syn. (C) A thin and long spine neck will have a high R_neck, which will locally boost the EPSP in the spine head. This in turn causes a loss of driving force, so that less current will flow over the synaptic conductance. While the EPSP in the spine head sees both the boosting and the loss of driving force, the corresponding EPSP in the dendrite only experiences the loss of driving force. Conversely, a spine with a low R_neck will see less boosting of the spine head EPSP and less current attenuation, so the spine and dendritic EPSPs are more similar. Beyond the illustrated passive effects of morphology, the boosted spine head EPSP may locally recruit voltage-gated conductances on the spine, which may in turn increase or decrease the synaptic current.

Figure 5

The impact of the spine neck resistance on EPSPs in spine heads and dendrites. The spine neck resistance has opposite effects on EPSPs in the spine head and in the dendrite. (A) For a given conductance, the neck will boost the spine head voltage, which in turn will reduce driving force and saturate the boosting effect. By contrast, in the dendrite, the neck no longer boosts the voltage, and only the reduced driving force is manifested as a decreasing voltage with increasing R_neck. Both effects are more pronounced for synapses with higher conductances, as these produce higher voltages and stronger reductions in driving force. (B) This simultaneous boosting and saturation effect of the neck is manifested as a reduced voltage per conductance (synaptic gain) as a function of R_neck, which is more pronounced for stronger synapses. Again, the dendrite sees only the saturation effect, while the spine voltage is also boosted. (C) Conversely, for a fixed R_neck value, increasing the synaptic conductance will boost both the spine and dendritic voltages, with an accordingly stronger saturation effect if R_neck is higher. From the different R_neck values plotted, it is evident that while R_neck boosts the spine voltage, it simultaneously attenuates the dendritic voltage.