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. 2021 Mar 2;11(1):4983.
doi: 10.1038/s41598-021-82353-7.

Analysis of segmentation ontology reveals the similarities and differences in connectivity onto L2/3 neurons in mouse V1

Alexander P Y Brown #  1 , Lee Cossell #  1 , Molly Strom  1 , Adam L Tyson  1 , Mateo Vélez-Fort  1 , Troy W Margrie  2
Affiliations

Analysis of segmentation ontology reveals the similarities and differences in connectivity onto L2/3 neurons in mouse V1

Alexander P Y Brown et al. Sci Rep. .

Abstract

Quantitatively comparing brain-wide connectivity of different types of neuron is of vital importance in understanding the function of the mammalian cortex. Here we have designed an analytical approach to examine and compare datasets from hierarchical segmentation ontologies, and applied it to long-range presynaptic connectivity onto excitatory and inhibitory neurons, mainly located in layer 2/3 (L2/3), of mouse primary visual cortex (V1). We find that the origins of long-range connections onto these two general cell classes-as well as their proportions-are quite similar, in contrast to the inputs on to a cell type in L6. These anatomical data suggest that distal inputs received by the general excitatory and inhibitory classes of neuron in L2/3 overlap considerably.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Global tree difference showing similarity of input to L2/3 relative to L6. (a) Schematic of experimental procedure. (b) Serial two-photon tomography was performed on each brain, and samples were aligned to and segmented according to the Allen Reference Atlas ontology. (c) Outline of the algorithm used for calculating the GTD. For each brain, the cell counts in each region are converted to a fraction of the total labelled inputs. For a pair of brains, for each region, the mean fraction, M, is then calculated, as well as the cosine difference (D) between the distribution of cells within the region’s subregions. Regions with only a single subregion are excluded from further processing. Next, for each region, the mean fraction is multiplied by the cosine difference, to give a weighted difference score (M*D). Finally, this weighted difference score is summed across all regions in the hierarchy and normalized by the sum of the mean fractions across all regions. This example is intended only to demonstrate the method described, and does not reflect the data in the present study. (d) Global tree difference for each pair of brains from within the same line (left), and for pairs of brains between (from left to right) gadOff and gadOn, gadOn and parv, gadOff and penk, gadOff and ntsr1, and penk and ntsr1.
Figure 2
Figure 2
Distribution of presynaptic input from isocortex to primary visual cortex (VISp). (a) Horizontal projections of a template brain, showing the positions, after registration, of presynaptically connected cells within the isocortex, for each mouse line. The number of cells displayed for each line is the same, and has been normalized to the line with the fewest inputs (gadOff) by randomly sampling from all isocortex inputs. Both contra- and ipsilateral inputs are displayed, although only ipsilateral inputs were used for analysis. Horizontal surface projection of the segmentation is shown. Areas comprising visual cortex are highlighted with thicker outlines. (b) Proportion of labelled rabies-infected cells in ipsilateral top-level areas of the isocortex, expressed as a fraction of all cells in isocortex. Inset, location of RSP, PTLp, AUD and SS on the horizonal surface projection of the segmentation. (c) Left, proportions of labelled cells in VISp (expressed as a fraction of all cells in visual cortex); right, proportions of labelled cells in different layers of VISp (expressed as a fraction of all cells in VISp). (d) Proportions of labelled cells in subregions of the visual cortex (higher visual areas), expressed as a fraction of all cells in visual cortex. Inset, location of each visual area in the horizontal segmentation. Error bars show the S.E.M. and data from individual mice are shown as dots overlaying the bars.
Figure 3
Figure 3
Distribution of presynaptic input from interbrain (IB) and hippocampal formation (HPF) to VISp. (a) Top, horizontal and sagittal projections, showing the distribution of labelled rabies-infected cells within the IB. Dashed lines indicate location of cross-section images, below. Bottom, coronal cross-sections of the template brain at three locations, with the position of labelled cells in the interbrain. Brain regions are outlined, and cells ± 20 μm anterior–posterior of the cross-section location are shown. Lateral preoptic area (LPO), lateral dorsal nucleus (LD), reticular nucleus (RT), lateral posterior nucleus (LP), and dorsal (LGd) parts of the lateral geniculate complex are indicated (in brackets, the parent regions of these regions). Numbers below indicate the number of cells from each line appearing in the image. (b) Sagittal projection showing the distribution of labelled cells within the HPF. Dashed lines indicate location of cross-section images, below. Below, coronal cross-sections of the template brain at three locations, with the position of labelled HPF cells and brain regions outlined (includes cells ± 10 μm anterior–posterior of the cross-section location). Pre- (PRE), post- (POST) and para- (PARA) subiculum, as well as lateral (ENTl) and medial (ENTm) entorhinal cortex are indicated. The dark grey region indicates a region labelled HPF with no further subdivision (NOS not otherwise specified). (c) Proportion of rabies-infected cells within the subregions of the interbrain (IB) and cortical plate (CTXpl). Error bars show the S.E.M. and data from individual mice are shown as dots overlaying the bars.
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