Receptor-driven, multimodal mapping of cortical areas in the macaque monkey intraparietal sulcus

Abstract

The intraparietal sulcus (IPS) is structurally and functionally heterogeneous. We performed a quantitative cyto-/myelo- and receptor architectonical analysis to provide a multimodal map of the macaque IPS. We identified 17 cortical areas, including novel areas PEipe, PEipi (external and internal subdivisions of PEip), and MIPd. Multivariate analyses of receptor densities resulted in a grouping of areas based on the degree of (dis)similarity of their receptor architecture: a cluster encompassing areas located in the posterior portion of the IPS and associated mainly with the processing of visual information, a cluster including areas found in the anterior portion of the IPS and involved in sensorimotor processing, and an 'intermediate' cluster of multimodal association areas. Thus, differences in cyto-/myelo- and receptor architecture segregate the cortical ribbon within the IPS, and receptor fingerprints provide novel insights into the relationship between the structural and functional segregation of this brain region in the macaque monkey.

Keywords: cytoarchitecture; intraparietal sulcus; multimodal map; myeloarchitecture; neuroscience; rhesus macaque; transmitter receptors.

Figure 1.. Parcellation of IPS areas in previous studies.

The IPS is unfolded. Blue lines represent the outline of the unfolded IPS, red line represents the fundus of the IPS. (A) Map after Seltzer and Pandya, 1986, Seltzer and Pandya, 1980. (B) Map after Preuss and Goldman-Rakic, 1991. (C) Map after Lewis and Van Essen, 2000a. (D) Map after Bakola et al., 2017. Abbreviations: IPS intraparietal sulcus, IPd intraparietal area (deep), PEa parietal area PEa, POa-i internal part of area POa, POa-e external part of area POa, AIP anterior intraparietal area, VIP ventral intraparietal area, VIPm ventral intraparietal area (medial part), VIPl ventral intraparietal area (lateral part), LIP lateral intraparietal area, LIPd lateral intraparietal area (dorsal), LIPv lateral intraparietal area (ventral), 7a-m, medial part of area 7a, 5V ventral part of area 5, MIP medial intraparietal area, PO parietal-occipital area, LOP lateral occipital parietal, PEip intraparietal part of PE, V6 visual area 6, V6Av visual area 6A (ventral part), V6Ad visual area 6A (dorsal part).

Figure 2.. Topography of IPS areas, and at the junction with POS.

Architectonic divisions are shown in a series of coronal cell body-stained sections from the left hemisphere of Macaca mulatta (DP1). The position of each section is highlighted on the lateral view of the left hemisphere. Abbreviations: IPS intraparietal sulcus, POS parietal-occipital sulcus, AIP anterior intraparietal area, VIPm ventral intraparietal area (medial part), VIPl ventral intraparietal area (lateral part), PEipe intraparietal part of PE (external part), PEipi intraparietal part of PE (internal part), LIPd lateral intraparietal area (dorsal), LIPv lateral intraparietal area (ventral), MIPd medial intraparietal area (dorsal), MIPv medial intraparietal area (ventral), V3d dorsal part of visual area 3, V3A visual area 3A, V4d dorsal part of visual area 3, LOP lateral occipital parietal, V6 visual area 6, V6Av visual area 6A (ventral part), V6Ad visual area 6A (dorsal part), PIP posterior intraparietal area.

Figure 3.. 2D cytoarchitectonic flat map of IPS areas in both hemispheres of Macaca mulatta.

Bold lines represent fundi of the intraparietal (IPS) and parieto-occipital (POS) sulci. Arabic numerals mark section numbers. For abbreviations see Figure 2.

Figure 4.. Cytoarchitecture of the 17 IPS areas.

Scale bar 300 μm. Roman numerals indicate cytoarchitectonic layers. For abbreviations, see Figure 2.

Figure 5.. Example of the identification of cytoarchitectonic borders for MIPd and MIPv.

(A) The black box on the overview of a coronal section processed for cell bodies indicates the location of the photomicrograph shown on the right. (B) The cortical ribbon was covered by traverses (from which GLI profiles were extracted) running perpendicular to the cortical layers; color changes between yellow and pink after every 10th traverse (left). Automatic labeling of the positions of the statistically defined borders (at position 32, 79 and 161) (middle). The position of borders of areas MIPd and MIPv as defined by visual inspection are indicated by white arrows in the corresponding image of the cell body stained section (right). (C) Exemplary Mahalanobis distance function depicting the Mahalanobis distances between neighboring blocks of 24 profiles; significant maxima occurred at profile positions 32, 79 and 161, which identify the borders of areas MIPd and MIPv (top). The significant maxima of varying block sizes (ranging from 10 to 24), indicate a consistently occurring border between both areas at profile location 79 (bottom). (D) High-resolution photomicrographs of cytoarchitectonic subdivisions MIPd and MIPv. Scale bar 200 μm. Roman numerals indicate cytoarchitectonic layers. Abbreviations: MIPd medial intraparietal area (dorsal), MIPv medial intraparietal area (ventral).

Figure 6.. Example of the identification of area MIPd based on receptor distribution patterns.

(A) Schematic representation of an autoradiograph in which the red box indicates the location of the exemplary autoradiographs (kainate, GABA_B and α₁ receptors) shown in (B) and (C). (B) The cortical ribbon was covered by traverses (from which profiles were extracted) running perpendicular to the cortical layers; color changes between yellow and pink after every 10th traverse (left). Automatic labeling of the positions of the statistically defined borders (right). (C) The position of borders of area MIPd as defined by visual inspection are indicated by white lines in corresponding pseudocolor coded autoardiographs. (D) Exemplary Mahalanobis distance function depicting the Mahalanobis distances between neighboring blocks of 20 profiles; significant maxima occurred at profile positions which coincide with borders for receptor architectonically defined area MIPd. (E) Laminar distribution patterns of corresponding receptors in areas MIPd and MIPv. Roman numerals indicate cytoarchitectonic layers. Abbreviations: MIPd medial intraparietal area (dorsal), MIPv medial intraparietal area (ventral).

Figure 6—figure supplement 1.. Cyto-, myelo- and receptor architecture of macaque MIPd.

The absolute receptor concentration (in fmol/mg protein) throughout the cortical depth is provided by the profile curve overlaid onto each receptor autoradiograph. Note, that the scale has been optimized for each profile to provide the best visualization of changes in receptor densities throughout the cortical ribbon. Roman numerals indicate cyto- and myeloarchitectonic layers, respectively. Positions of cytoarchitectonic layers were transferred to the neighboring receptor images.

Figure 6—figure supplement 2.. Cyto-, myelo- and receptor architecture of macaque MIPv.

For further details, see Figure 6—figure supplement 1.

Figure 7.. Example of the identification of cytoarchitectonic borders for PEipe and PEipi.

(A) The black box on the overview of a coronal section processed for cell bodies indicates the location of the photomicrograph shown on the right. (B) The cortical ribbon was covered by traverses (from which GLI profiles were extracted) running perpendicular to the cortical layers; color changes between yellow and pink after every 10th traverse (left). Automatic labeling of the positions of the statistically defined borders (at position 20, 94 and 148) (middle). The position of borders of areas PEipe and PEipi as defined by visual inspection are indicated by white arrows in the corresponding image of the cell body stained section (right). (C) Exemplary Mahalanobis distance function depicting the Mahalanobis distances between neighboring blocks of 20 profiles; significant maxima occurred at profile positions 20, 94 and 148, which identify the borders of areas PEipe and PEipi (top). The significant maxima of varying block sizes (ranging from 10 to 24), indicate a consistently occurring border between both areas at profile location 94 (bottom). (D) High-resolution photomicrographs of cytoarchitectonic subdivisions PEipe and PEipi. Scale bar 200 μm. Roman numerals indicate cytoarchitectonic layers. Abbreviations: PEipe intraparietal part of PE (external part), PEipi intraparietal part of PE (internal part).

Figure 8.. Example of the identification of areas PEipi and PEipe based on receptor distribution patterns.

(A) Schematic representation of an autoradiograph in which the red box indicates the location of the exemplary autoradiographs (M₂ M₃ and α₁ receptors) shown in (B) and (C). (B) The cortical ribbon was covered by traverses (from which profiles were extracted) running perpendicular to the cortical layers; color changes between yellow and pink after every 10th traverse (left). Automatic labeling of the positions of the statistically defined borders (right). (C) The position of borders of areas PEipi and PEipe as defined by visual inspection are indicated by white lines in corresponding pseudocolor coded autoardiographs. (D) Exemplary Mahalanobis distance function depicting the Mahalanobis distances between neighboring blocks of 20 profiles; significant maxima occurred at profile positions which coincide with borders for receptor architectonically defined areas PEipi and PEipe. (E) Laminar distribution patterns of corresponding receptors in areas PEipi and PEipe. Roman numerals indicate cytoarchitectonic layers. Abbreviations: PEipe intraparietal part of PE (external part), PEipi intraparietal part of PE (internal part).

Figure 8—figure supplement 1.. Cyto-, myelo- and receptor architecture of macaque PEipe.

For further details, see Figure 6—figure supplement 1.

Figure 8—figure supplement 2.. Cyto-, myelo- and receptor architecture of macaque PEipi.

For further details, see Figure 6—figure supplement 1.

Figure 9.. Myeloarchitecture of areas of the IPS.

Coronal sections through four rostro-caudal levels of a macaque hemisphere showing the myeloarchitecture of the IPS. For abbreviations, see Figure 2.

Figure 10.. Example of receptor distribution patterns in the IPS.

Coronal sections through four rostro-caudal levels of a macaque hemisphere showing exemplary receptor distribution patterns in the IPS. Receptor distribution patterns illustrated for all 15 receptors are shown in Figure 10—figure supplements 1–4. The borders between the IPS areas (red lines) are charted on the pseudocolor-coded autoradiographs. The color bar beneath each autoradiograph indicates receptor concentrations by the different colors, from black for low to red for high concentrations (fmol/mg protein). For abbreviations, see Figure 2.

Figure 10—figure supplement 1.. Receptor distribution patterns in the junction of the IPS and POS.

Receptor distribution patterns in areas MIPd, V6Ad, V6Av, V6, V3d, V3A, V4d, LOP and LIPv illustrated for 15 receptors studied. The borders between IPS areas (red lines) are charted on the pseudocolor-coded autoradiographs. The color bar beneath each autoradiograph indicates receptor concentrations by the different colors, from black for low to red for high concentrations (fmol/mg protein). For abbreviations, see Figure 2. Red box on the left section indicates the location of the region of interest.

Figure 10—figure supplement 2.. Receptor distribution patterns in the caudal IPS.

Receptor distribution patterns in areas MIPd, MIPv, V6Av, PIP, V3d, V3A, LOP, LIPv and LIPd illustrated for the 15 receptors studied. For further details, see Figure 10—figure supplement 1.

Figure 10—figure supplement 3.. Receptor distribution patterns in the middle portion of the IPS.

Receptor distribution patterns in areas PEipe, PEipi, VIPm, VIPl, LIPv and LIPd illustrated for the 15 receptors studied. For further details, see Figure 10—figure supplement 1.

Figure 10—figure supplement 4.. Receptor distribution patterns in the rostral portion of the IPS.

Receptor distribution patterns in area AIP illustrated for the 15 receptors studied. For further details, see Figure 10—figure supplement 1.

Figure 11.. Receptor fingerprints of the examined brain areas.

Absolute densities in fmol/mg protein of 15 receptors are displayed in polar coordinate plots (scaling 0–2000 fmol/mg protein). For aesthetical reasons, the standard deviations are not displayed in the fingerprints. For mean (and s.d.) densities of each area and receptor type see Table 1. The positions of the different receptor types and the axis scaling are identical in all polar plots, and specified in the polar plot at the top left corner of the figure. For abbreviations, see Figure 2.

Figure 11—figure supplement 1.. Normalized receptor fingerprints of the examined brain areas.

Polar plots (scaling −0.6/+0.6) showing the normalized receptor concentration of all 15 receptors. Normalization of the receptor concentrations was calculated based on each receptor’s mean over all IPS areas. Black thick line indicates the position where the receptor concentration was equal to the mean receptor concentration averaged over all IPS areas.

Figure 12.. Receptor-driven clustering of the IPS subdivisions.

(A) Hierarchical cluster analysis reveals 3 receptor-architectonically distinct clusters: a caudal cluster with visual areas (blue); an intermediate group of areas VIPm, VIPl and V6Ad (pink); and a rostral group consisting of all areas located on the bilateral walls of IPS (red). (B) Three clusters are displayed in the 2D flat map, same color coding as in (A). (C) Principal component analysis. The distances between areas represent the Eigenvalues of the first and second principal components, three clusters are clearly segregated by the first and second principal component, same color coding as in (A) and (B). For abbreviations, see Figure 2.

Figure 13.. Inter-individual variability in the position of the V3d/V3A border.

Schematic representation of an exemplary parasagittal section located 10 mm to the right of the midline, on which variations in the position of the V3d/V3A border in relation to the anectant gyrus are illustrated (A, B, C). Dashed lines indicate the rostro-caudal position of the coronal sections shown below and which are located 9 mm (A1, B1, C1), 10 mm (A2, B2, C2) and 11 mm (A3, B3, C3) caudal to the interaural surface (Saleem and Logothetis, 2012). (A1–A3) Schematic representation of areas found on the anectant gyrus when the V3d/V3A border was detected on its rostral wall (A). (B1–B3) Schematic representation of areas found on the anectant gyrus when the V3d/V3A border was detected on its apex (B). (C1–C3) Schematic representation of areas found on the anectant gyrus when the V3d/V3A border was detected on its caudal wall (C). Abbreviations: a anterior, cas calcarine sulcus, d dorsal, ips intraparietal sulcus, l lateral, lus lunate sulcus, m medial, p posterior, pos parieto-occipital sulcus, v ventral.