Introduction. We are developing receptor architectonic rat brain maps to expand the Waxholm Space Atlases of the Rat Brain with functionally relevant data. This study focused on the development of 3D maps of the whole rat iso and proisocortex, regarding the heterogeneous distribution of glutamatergic (AMPA, kainate, NMDA), serotoninergic (5 HT1A, 5 HT2), adrenergic α1 and muscarinic (M2, M3) receptors and their correlation with cytoarchitectonic borders.
Methods. Alternating coronal serial sections (thickness 20 µm) through entire rat brains are used for silver cell-body staining and quantitative in vitro autoradiographic labeling of eight receptor types to identify cortical borders based on cyto and receptor architectonic heterogeneities, respectively. Mean receptor densities were measured in each identified area, and the ensuing parcellation brought into the Waxholm Rat Atlas stereotaxic space1.
Results and Conclusion. Over 50 distinct areas were identified in the rat iso- and proisocortex based on multimodal analysis of the regional and laminar differences in cytoarchitecture and eight different receptors. The isocortex encompasses frontal areas Fr1-Fr3, FrHL, FrFL; parietal areas Par1, Par2, ParHL and ParFL, ventral and posterior parietal areas (ParVr, ParVc and ParPd, ParPv, respectively); granular insular areas GIa, GIp; temporal areas Te1, Te2d, Te2v, Te3r and Te3v; occipital areas Oc1B, OC1M, medial areas Oc2MM and Oc2ML and lateral areas Oc2Lr, Oc2Lc, Oc2Lid and Oc2Liv; and finally, ectorhinal areas EctD and EctV. Within the proisocortex we identified orbitofrontal areas DLO, LO, VLO, VO and MO; cingulate areas Cg1, Cg1’, Cg2d, Cg2d’, Cg2v, Cg2v’, Cg3; agranular retrosplenial area RSA; dysgranular insular DI; posterior ectorhinal EctP and dorsal and ventral perirhinal areas PRhD and PRhV. As described in primates, rat primary sensory areas represented different receptor distribution patterns e.g., higher M2 and 5 HT2 receptor densities in layer IV, which is the main target of sensory input. Contrarily, kainate and α1 receptors showed lower densities in layer IV. Additionally. to the frontal areas Fr1 and Fr2, FrHL and FrFL were marked by higher mean densities of the eight investigated receptor types. Whereas the heterogenous laminar distributions of kainate, M2, M3 and 5 HT2 receptors represented the borders to the adjacent areas ParHL, ParFL and further the whole parietal cortex. Differences (e.g., AMPA), as well as homologies (e.g., NMDA) in receptor architecture were analyzed within the rat cingulate and retrosplenial areas, compared to primates.
The ensuing map can be used for cyto and receptor architectonically informed analyses of future in vivo studies via the Waxholm Rat Atlas stereotaxic space3, and thus constitutes a valuable resource for the neuroscientific community.