Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human
- Ruhr University Bochum, Faculty of Biology and Biotechnology, Developmental Neurobiology, Germany
- Heidelberg University, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience, Institute of Neuroanatomy, Germany
- JARA-Institute Brain Structure Function Relationship, Germany
- Johannes Kepler University Linz, Faculty of Medicine, Institute of Anatomy and Cell Biology, Austria
- Ruhr University Bochum, Faculty of Biology and Biotechnology, Zoology and Neurobiology, Germany
- University of La Laguna, Faculty of Medicine, Department of Basic Medical Science, Spain
Figures
Figure 1
Confocal tile scan of dorsal neocortex (premotor area) of P60 infant macaque.
(A) Pyramidal cells were stained with SMI-32/βIV-spectrin to label dendrites and the axon initial segment, respectively. Insets depict neurons with an axon emerging from the soma (B), or from an …
Figure 2 with 5 supplements
Representative axon carrying dendrite (AcD) neurons.
(A1, A2) From rat visual cortex (biocytin, immunofluorescence); (B1, B2) cat visual cortex (immunofluorescence); (C1, C2) ferret visual cortex (biocytin); (D1, D2) macaque premotor cortex (biocytin, …
Figure 2—figure supplement 1
Variations of axon origins of biocytin-stained pyramidal neurons of rat (A–D) and ferret (E–G) visual cortex, and macaque premotor cortex (H–K), and macaque intraparietal sulcus (L).
The neurons in (L), an AcD cell next to a somatic axon cell, reside millimeters from the injection site, they are long projecting layer III pyramidal neurons. Cells with somatic axons are in B, …
Figure 2—figure supplement 2
Variations of axon origins of Golgi-impregnated pyramidal neurons of human temporal cortex, all taken from Individual 2, 56 years of age and sampled from all layers.
Cells with somatic axons are in A, B, C, D, E, F. Cells with shared root configuration are in G, H, I. Cells with axon carrying dendrites are J, K, L, M, N, O. Axons marked by white arrows, axon …
Figure 2—video 1
Neuron classified as AcD cell in macaque cortex.
Figure 2—video 2
Neuron classified as shared root cell in macaque cortex.
Figure 2—video 3
Neuron classified as Von Economo neuron in macaque cortex.
Figure 3
Proportion of axon carrying dendrite (AcD) neurons across species.
(A) Shown are mean ± SEM. of the individual percentages listed in Tables 1–4, which also indicate the staining methods. Numbers above the bars are the total number of pyramidal neurons assessed per …
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Figure 3—source data 1
Data and statistical analysis of experiments shown in Figure 3A, B.
- https://cdn.elifesciences.org/articles/76101/elife-76101-fig3-data1-v2.xlsx
Figure 4
Within-species areal comparisons.
(A) Upper left is a photomicrograph of one of the coronal sections stained for immunofluorescence. The regions of interest are color coded. Upper right is the macaque brain (after Paxinos et al., …
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Figure 4—source data 1
Data and statistical analysis of experiments shown in Figure 4A and B.
- https://cdn.elifesciences.org/articles/76101/elife-76101-fig4-data1-v2.xlsx
Figure 5
Proportion of axon carrying dendrite (AcD) cells versus shared root cells.
(A) Data from rat (biocytin), ferret (biocytin), macaque (biocytin, immunofluorescence, Golgi), and human (Golgi). The species cluster along the ordinate as already seen in Figure 3B. The …
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Figure 5—source data 1
Data and statistical analysis of experiments shown in Figure 5A and B.
- https://cdn.elifesciences.org/articles/76101/elife-76101-fig5-data1-v2.xlsx
Figure 6
Spine density did not systematically differ between regular dendrites (non-axon carrying dendrites [non-AcDs]), dendrites sharing a root with a neighboring axon, and AcDs.
Data from adult rat and ferret biocytin material, values from each cell are connected by a line.
For normalization, the average of the non-AcD has been set to 1, and all values were expressed relative to this. Mann-Whitney rank sum test p-values and the sample size are reported above each plot.
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Figure 6—source data 1
Data and statistical analysis of experiments shown in Figure 6.
- https://cdn.elifesciences.org/articles/76101/elife-76101-fig6-data1-v2.xlsx
Figure 7
Axon carrying dendrite (AcD) interneurons in human and cat cortex.
(A) Photomicrograph of a representative Golgi-impregnated bitufted neuron with arcade-like initial axon from supragranular layers next to its reconstruction, followed by three further examples of …
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Figure 7—source data 1
Data and statistical analysis of experiments shown in Figure 7A and B.
- https://cdn.elifesciences.org/articles/76101/elife-76101-fig7-data1-v2.xlsx
Author response image 1
Tables
Table 1
Proportion of pyramidal neurons with AcD: rodents.
| Species; cortical area; staining method; age; sex | Proportion of AcD cells [%];n of cells assessed | By layers: supra %, infra % |
|---|---|---|
| Mouse S1 cortex, layer V;Thy1-EGFP/βIV-spectrin immunofluorescence | ||
| Adult, female | 17.42%, 178 cells | n.a. |
| Adult, female | 11.78%, 348 cells | n.a. |
| Adult, female | 15.79%, 36 cells | n.a. |
| Adult, female | 18.84%, 138 cells | n.a. |
| Adult, male | 21.93%, 187 cells | n.a. |
| Adult, male | 14.82%, 54 cells | n.a. |
| Adult, male | 10.17%, 59 cells | n.a. |
| Average [%], total n of cells | 15.82%, 1000 cells | |
| Rat visual cortex; biocytin tracing | ||
| Adult, male, two hemispheres | 17.82%, 174 cells | 15.06%, 17.69% |
| Adult, male, two hemispheres | 15.07%, 803 cells | 15.65%, 16.46% |
| Average [%], total n of cells | 16.45%, 977 cells | 15.36%, 17.08% |
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AcD, axon carrying dendrite; n.a., not applicable.
Table 2
Proportion of pyramidal neurons with AcD: ungulate, carnivores.
| Species; cortical area; staining method; age; sex | Proportion of AcD cells [%];n of cells assessed | By layers: supra %, infra % |
|---|---|---|
| Kitten visual cortex gyral white matter; intracellular Lucifer yellow | ||
| P1, P2 (n = 2, sex n.d.) | 37.93%, 58 cells | n.a. |
| P10, P11 (n = 2, sex n.d.) | 44.64%, 56 cells | n.a. |
| P12, P14 (n = 2, sex n.d.) | 47.37%, 19 cells | n.a. |
| Average [%], total n of cells | 43.31%, 133 cells | |
| Kitten and adult cat visual cortex layer VI; intracellular Lucifer yellow | ||
| P1, P5 (n = 2, sex n.d.) | 20.18%, 114 cells | n.a. |
| P11 (n = 2, sex n.d.) | 17.65%, 51 cells | n.a. |
| P19, P30 (n = 2, sex n.d.) | 14.89%, 47 cells | n.a. |
| P52, P60 (n = 2, sex n.d.) | 20.00%, 30 cells | n.a. |
| Adult (n = 2, sex n.d.) | 17.95%, 39 cells | n.a. |
| Average [%], total n of cells | 18.13%, 281 cells | |
| Adult cat visual cortex;SMI-32/βIV-spectrin immunofluorescence | ||
| Individual 1, 3 months, sex n.d. | 13.35%, 978 cells | 14.42%, 14.55% |
| Individual 2, adult, sex n.d. | 14.92%, 496 cells | n.d. |
| Adult cat visual cortex; biocytin tracing | ||
| Individual 3, adult, sex n.d. | 13.44%, 655 cells | 12.50%, 15.85% |
| Individual 4, adult, sex n.d. | 17.14%, 70 cells | 18.52%, 12.50% |
| Individual 5, adult, sex n.d. | 13.93%, 316 cells | 13.12%, 15.79% |
| Individual 6, adult, sex n.d. | 19.13%, 230 cells | 19.34%,18.37% |
| Individual 7, adult, sex n.d. | 12.64%, 174 cells | 11.49 %, 19.23% |
| Average [%] individuals 1–7, total n of cells | 14.94%, 2919 cells | 14.90%, 16.05% |
| Ferret visual cortex; biocytin tracing | ||
| Individual 1, adult, female | 16.56%, 302 cells | 15.95%, 18.57% |
| Individual 2, adult, female | 14.66%, 191 cells | 15.39%, 13.11% |
| Individual 3, adult, female | 11.30%, 230 cells | 10.24%, 14.06% |
| Individual 4, adult, male | 13.07%, 329 cells | 13.45%, 12.26% |
| Average [%], total n of cells | 13.90%, 1052 cells | 13.76%, 14.50% |
| Pig dorsoparietal cortex;SMI-32/βIV-spectrin immunofluorescence | ||
| 3 months, European wild boar, female | 20.11%, 189 cells | 22.04%, 19.05% |
| 5 months, domestic, sex n.d. | 20.99%, 181 cells | n.d. |
| Average [%], total n of cells | 20.55%, 370 cells | 22.04%, 19.05% |
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AcD, axon carrying dendrite; n.a., not applicable; n.d., not determined due to too weak staining.
Table 3
Proportion of pyramidal neurons with AcD: primates - macaque.
| Species; cortical area; staining method; age; sex | Proportion of AcD cells [%];n of cells assessed | By layers: supra %, infra % |
|---|---|---|
| Macaca mulatta premotor cortex; biocytin tracing | ||
| Individual 1, 11 years, male | 4.93%, 954 cells | 2.79%, 11.38% |
| Individual 2, 7 years, male | 3.10%, 816 cells | 2.93%, 6.32% |
| Individual 3, 5 years, male | 4.26%, 423 cells | 3.23%, 6.25% |
| Macaca mulatta parietal and visual cortex; SMI-32/βIV-spectrin immunofluorescence | ||
| Individual 4, 5 years, male | 5.99%, 717 cells | 2.59%, 13.95% |
| Individual 5, 10 years, male | 6.75%, 681 cells | 2.51%, 12.72% |
| Macaca fascicularis parietal cortex;Golgi-Kopsch method | ||
| Individual 6, adult, female | 3.58%, 307 cells | 4.82%, 6.90% |
| Individual 7, adult, male | 3.07%, 228 cells | 1.57%, 5.67% |
| Average [%] individuals 1–7, total n of cells | 4.53%, 4126 cells | 2.92%, 9.03% |
| Macaca mulatta visual cortex; biocytin tracing | ||
| Individual 8, P60, female | 4.51%, 377 cells | 1.28%, 5.88% |
| Macaca mulatta cingulate cortex;SMI-32/βIV-spectrin immunofluorescence | ||
| Individual 8, P60, female | 5.80%, 500 cells | 1.28%, 7.85% |
| Macaca mulatta premotor/M2 cortex;SMI-32/βIV-spectrin immunofluorescence | ||
| Individual 8, P60, female | 5.36%, 1249 cells | 1.34%, 9.05% |
| Average [%] individual 8, total n of cells | 5.22%, 2126 cells | 1.30%, 7.59% |
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AcD, axon carrying dendrite.
Table 4
Proportion of pyramidal neurons with AcD: primates - human.
| Species; cortical area; staining method; age; sex | Proportion of AcD cells [%];n of cells assessed | By layers: supra %, infra % |
|---|---|---|
| Human temporal lobe;Golgi-Cox method | ||
| Individual 1, 53 years, male | 2.56%, 646 cells | 1.45%, 4.40% |
| Individual 2, 56 years, male | 2.79%, 825 cells | 0.96%, 4.66% |
| Human auditory cortex;Golgi-Kopsch method | ||
| Individual 3, 63 years, male | 0.79%, 253 cells | 0.69%, 0.91% |
| Individual 4, 71 years, female | 1.92%, 677 cells | 0.80%, 2.58% |
| Individual 5, 75 years, male | 0.47%, 215 cells | 0.00%, 0.80% |
| Individual 6, 88 years, female | 0.71%, 140 cells | 0.00%, 1.28% |
| Individual 7, 56 years, female | 1.72%, 407 cells | 1.27%, 2.34% |
| Human prefrontal agranular cortex;Golgi-Kopsch method | ||
| Individual 8, 46 years, female | 2.02%, 247 cells | n.d. |
| Individual 9, 77 years, male | 2.59%, 424 cells | n.d. |
| Individual 10, 87 years, female | 1.53%, 653 cells | n.d. |
| Human visual cortex area 18Golgi-Kopsch method | ||
| Individual 10, 87 years, female | 2.48%, 242 cells | 1.77%, 3.10% |
| Average [%] individuals 1–10, total n of cells | 1.96%, 4729 cells | 0.99%, 2.87% |
| Human auditory cortex gyral white matter;Golgi-Kopsch method | ||
| Individual 3, 63 years, male | 8.69%, 115 cells, | n.a. |
| Individual 4, 71 years, female | 8.88%, 135 cells, | n.a. |
| Individual 5, 75 years, male | 8.70%, 69 cells, | n.a. |
| Individual 6, 88 years, female | 9.18%, 98 cells, | n.a. |
| Average [%] individuals 3–6, total n of cells | 8.86%, 417 cells | n.a. |
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AcD, axon carrying dendrite.
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Antibody | anti-βIV-spectrin (Rabbit polyclonal) | Höfflin et al., 2017 | self-made | IF (1:500) |
| Antibody | anti-SMI-32 unphosphorylated neurofilaments (Mouse polyclonal) | Covance, Muenster, Germany | Cat # SMI-32r, RRID: AB_2315331 | IF (1:1000) |
| Antibody | anti-NeuN(Mouse monoclonal) | Merck (Millipore), Darmstadt, Germany | Cat # MAB377,RRID: AB_2298772 | IF (1: 1000) |
| Antibody | anti-Parvalbumin,(Rabbit recombinant) | SWANT, Marly Switzerland | Code No. PV 27 | IHC (1:5000) |
| Antibody | donkey anti-rabbit (Alexa-488 polyclonal) | Thermo Scientific, Waltham MA, USA | RRID: AB_2687506 | IF (1:1000) |
| Antibody | goat anti-rabbit (biotinylated polyclonal) | Dako A/S, Glostrup, Denmark | RRID: AB_2313609 | IHC (1:1000) |
| Antibody | goat, anti-mouse(Alexa-568 polyclonal) | Invitrogen, Carlsbad, CA, USA | RRID: AB_2534013 | IF (1:1000) |
| Antibody | sheep anti-mouse (biotinylated polyclonal) | GE Healthcare Life Sciences, Braunschweig Germany, | Amersham Cat # RPN1001 | IHC (1:200) |
| Chemical compound, drug | Streptavidin Alexa-488 | Thermo Scientific, Waltham MA, USA | Cat #S11223 | (1:1000) |
| Chemical compound, drug | ABC Elite horseradish peroxidase | Vector Labs Inc, Burlingame, CA, USA, | RRID: AB_2336827 | (1:250) |
| Other | DAPI stain | Invitrogen | D1306 | (1 µg/mL) |
| Software, algorithm | SigmaStat 12.3 | Systat Software GmbH | Frankfurt am Main, Germany |
