Geometry and the Organizational Principle of Spine Synapses along a Dendrite

Morphometric analysis of dendritic spines in multiple brain regions. Box and whiskers plots show that the spine head volume (A), spine neck length (B), and spine neck diameter (C) are highly variable, and there exists a significant overlap in their dimensions across different brain regions. Note that, compared with other brain regions, the dendritic spines in CB display much less variability in spine head volume. D, The bar graph shows that the ratio of PSD area to neck length is not significantly different between spines in the CA1 PSR and CB. Error bars indicate SEM. E, 3D plot shows that the dendrites from CA1 PSR, CA1 SLM, cortex, striatum, and CB are not easily distinguishable from each other based on the analysis of the average neck diameter, average PSD area, and average neck length of their spines. F, Box and whiskers plot shows that the spine density is high in the CB, moderate in the CA1 PSR and striatum, and low in the CA1 SLM and cortex. Mean values are indicated by + mark in A–C, F. The box shows 25th, 50th, and 75th percentiles of the dataset. In each graph, a significant difference exists in the spine dimensions between any pair of brain regions not designated as n.s. (not significant). Extended Data Figure 2-1 shows that the spine head volume correlates strongly with the PSD area, but only weakly with the neck length. A linear positive correlation between the amplitude of uEPSC and the spine head volume is shown in Extended Data Figure 2-2. A scatter plot in Extended Data Figure 2-3 shows that the dendrites in the CA1 PSR can be grouped in two distinct populations based on their dendritic diameter.

Spines are organized in a regulated manner in the dendrites. A, PSD area unit dendritic length shows a significant positive correlation with the dendritic diameter in the CA1 PSR, cortex, and CB (see also Extended Data Fig. 3-1). However, in the striatum, the PSD area unit dendritic length does not correlate with dendritic diameter. B, Neck length unit dendritic length is positively correlated with the dendritic diameter in the CA1 PSR. The data from CA1 PSR, cortex, and striatum are plotted in reference to the left vertical axis, and the data from CB are plotted in reference to the right vertical axis in panels A, B. Average PSD area (C), and average neck length (D) show a positive correlation with the dendritic diameter in the CA1 PSR. Scatter plots in Extended Data Figure 3-2 show that the ratio of the total PSD area to total neck length (A), and the average neck diameter (B) do not correlate with the dendritic diameter in the CA1 PSR. Extended Data Figure 3-3 shows that the synaptic constancy enables effective information transfer from the dendrite to the soma.[enu-eN-NWR-0248-20-s06.tif]

Spine neck strongly filters membrane potential on CA1 pyramidal neurons. A, Two-photon image of a dendritic segment showing the spines (blue crosses: spines of similar head size, but different neck length; red crosses: spines of different head size, but similar neck length) receiving glutamate uncaging stimulus. uEPSPs were evoked by glutamate uncaging test pulses (5–10 trials at 0.1 Hz). Blue and red traces are representative uEPSPs from blue and red targets, respectively. B, Quantitative analyses of the estimated spine volume, spine length to width ratio, and uEPSPs of long (filled bars) and short (open bars) neck spines (n = 35 spines in each group, 6 cells). Error bars indicate SEM; n.s., not significant. See Extended Data Figure 4-1 for the relationship of the uEPSP amplitude with the spine neck length and the head width.

Intrapair synapse sizes are similar in axon-coupled spine pairs. A, 3D reconstruction of a cortical axon (medium slate blue) that makes synaptic contacts with spines from multiple dendrites. B, An example of an axon in the CA1 PSR that makes synaptic contacts with two spines (shown by white arrows) from the same dendrite. C, An example of a parallel fiber in CB making synaptic contacts with three different spines from the same dendrite. D, An example of a climbing fiber in CB making synaptic contacts with seven different spines (turquoise protrusions from the dendrite) from the same dendrite. PSD areas of axon-coupled spine pairs are positively correlated in the CA1 PSR (E) and CB (F). Scale cubes: 0.5 μm for each side.