Class-Specific Features of Neuronal Wiring

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Class-Specific Features of Neuronal Wiring Armen Stepanyants, Gábor Tamás, Dmitri B Chklovskii  Neuron  Volume 43, Issue 2, Pages 251-259 (July 2004) DOI: 10.1016/j.neuron.2004.06.013

Figure 1 Specific and Nonspecific Layout of Branches (A) Nonspecific layout. Schematic 2D illustration of an axon (blue line) passing through the neuropil containing dendrites of neurons postsynaptic to that axon (red circles) and other dendrites (black circles). The axon comes into close proximity with dendrites of both classes, showing no preference for one class over the other. (B) Specific branch layout can be achieved with tortuosity (left) and branching (right). Here, axon specifically targets postsynaptic dendrites (red circles). (C) Axons of GIs are significantly more tortuous than dendrites of PCs and GIs for all values of segment length, L. In contrast, PC axons are significantly less tortuous than PC and GI dendrites. Inset illustrates how T is calculated. Blue line represents neuronal branch. Branch segment of length L is in red. (D) Branches of PC axons are significantly longer than branches of PC and GI dendrites (*p < 10−4, Student's t test for unequal variances). Branches of GI axons are significantly shorter than dendritic branches of PCs and GIs (**p < 10−8). Error bars in (C) and (D) represent standard errors of the mean. Neuron 2004 43, 251-259DOI: (10.1016/j.neuron.2004.06.013)

Figure 2 Potential Synapses (A) A 3D reconstruction (part of the triplet from Figure S1 in the Supplemental Data [http://www.neuron.org/cgi/content/full/43/2/251/DC1]) of PC dendrite (red) and regular spiking nonpyramidal cell axon (blue). Scale bar, 100 μm. (B) A magnification of the circled region in (A). Potential synapses between the arbors are shown with small black circles. (C) Further magnification of a potential synapse in (B). Potential synapse is a location in neuropil where an axonal branch is present within the correlation scale s of a dendrite. (D) Number of potential synapses as functions of the correlation scale s for all 46 GI axon and PC or GI dendrite arbor pairs from Table 1 (thin lines). The average number of potential synapses is a linearly increasing function of the correlation scale (thick red line). Neuron 2004 43, 251-259DOI: (10.1016/j.neuron.2004.06.013)

Figure 3 Principles of the Shift Method (A) A small region of overlapping axonal and dendritic arbor pairs (same as Figure 2B) is shown on the left with five identified potential synapses (black circles). After a small random shift of the axon (in blue) the number of new potential synapses is two (right). Arrow showing the direction of the shift randomly chosen from the 30 μm cube. (B) Control distribution for the number of potential synapses at s = 0.5 μm for the arbor pair from Figure 2A. The arbors are positively correlated since the observed numbers of potential synapses is larger than the mean of the control distribution. The absolute value of the arbor correlation coefficient C is provided by twice the area under the control distribution, between the mean and the observed numbers of potential synapses (shaded area). (C) C as a function of correlation scale, s, for the same arbor pair. The arrow points to correlation scale s = 0.5 μm, corresponding to the distribution in (B). Neuron 2004 43, 251-259DOI: (10.1016/j.neuron.2004.06.013)

Figure 4 Average Arbor Correlation Coefficient and Cumulative p Value (A) Individual (thin lines) and the average (thick red line) arbor correlation coefficients as functions of s for all 46 GI axon and GI or PC dendrite arbor pairs from Table 1. The color code is the same as in Figure 2D. (B) Arbor correlation coefficients of 22 PC axon and GI or PC dendrite arbor pairs. The right axes in (A) and (B) indicate the probability of finding higher average correlation by chance, cumulative p value. Axons of GIs show significant average correlation with neighboring dendrites at all values of the correlation scale s. In contrast, no significant average correlation is detected in the layout of PC axons. Neuron 2004 43, 251-259DOI: (10.1016/j.neuron.2004.06.013)

Figure 5 Arbor Correlation Coefficients and Average Correlation Magnitude M in the Shaft and Spine Bins (A) Individual (thin lines) and the average (thick red line) arbor correlation coefficients in the shaft and spine bins for all 46 GI axon and GI or PC dendrite arbor pairs from Table 1. (B) Arbor correlation coefficients in the shaft and spine bins for 22 PC axon and GI or PC dendrite arbor pairs. The right axes in (A) and (B) indicate the probability of finding higher average correlation by chance, pcum. The color code is the same as in Figures 4A and 4B. There is a significant positive correlation in (A) in the shaft bin at pcum < 0.0005. (C and D) Average correlation magnitudes in the shaft and spine bins for GI-to-all and PC-to-all pairs from (A) and (B), correspondingly. * indicates significance based on pcum. Error bars denote the standard errors of the means. Neuron 2004 43, 251-259DOI: (10.1016/j.neuron.2004.06.013)

Figure 6 Results of the Correlation Analysis of a Hierarchy of Connection Types (A) GI-to-all pairs are first divided into three classes according to connectivity: connected, potential self-innervations, and unconnected. These classes are further subdivided into connected and unconnected GI-to-PC and GI-to-GI pairs. In each of the resulting classes, correlation magnitude is calculated in the shaft and spine bin (mean ± SEM). Highlights indicate significant correlation detected with the shift method. n is the numbers of analyzed pairs in each class. (B) A hierarchy of connection types for PC axon. No significant correlation is found in this case. Small numbers of pairs preclude the analysis of connected and unconnected PC-to-PC and PC-to-GI pairs. Neuron 2004 43, 251-259DOI: (10.1016/j.neuron.2004.06.013)

Figure 7 Summary Diagram of Specificity in Axonal and Dendritic Branch Layout of PCs and GIs (A) Specificity of PC axons. Axons of PCs have longer and less tortuous branches compared to GI axons. These axons show no correlation with the positions of the dendrites of their postsynaptic neurons, and as a result appear to be nonspecific. However, specificity in PC-to-PC connectivity can be achieved by selective growth of PC dendritic spines. (B) Specificity of GI axons. Axons of GIs are positively correlated with the positions of their postsynaptic PC or GI dendritic targets, which provides a substrate for specificity. PC and GI axons are in blue; their postsynaptic dendritic targets, which include PC dendrites (with spines) and GI dendrites (no spines), are in red. All other dendrites are black. Neuron 2004 43, 251-259DOI: (10.1016/j.neuron.2004.06.013)