Bhagwandin, AdhilMolnar, ZoltanBertelsen, Mads F.Karlsson, Karl Æ.Alagaili, Abdulaziz N.Bennett, Nigel CharlesHof, Patrick R.Kaswera-Kyamakya, ConsolateGilissen, EmmanuelJayakumar, JaikishanManger, Paul R.2025-03-282025-03-282024-07Bhagwandin, A., Molnar, Z., Bertelsen, M.F. et al. 2024, 'Where do core thalamocortical axons terminate in mammalian neocortex when there is no cytoarchitecturally distinct layer 4?', Journal of Comparative Neurology, vol. 532, art. e25652, pp. 1-22. https://DOI.org/10.1002/cne.25652.0021-9967 (print)1096-9861 (online)10.1002/cne.25652http://hdl.handle.net/2263/101795DATA AVAILABILITY STATEMENT : Data have not been shared due to this study being based on histological sections.Although the mammalian cerebral cortex is most often described as a hexalaminar structure, there are cortical areas (primary motor cortex) and species (elephants, cetaceans, and hippopotami), where a cytoarchitecturally indistinct, or absent, layer 4 is noted. Thalamocortical projections from the core, or first order, thalamic system terminate primarily in layers 4/inner 3. We explored the termination sites of core thalamocortical projections in cortical areas and in species where there is no cytoarchitecturally distinct layer 4 using the immunolocalization of vesicular glutamate transporter 2, a known marker of core thalamocortical axon terminals, in 31 mammal species spanning the eutherian radiation. Several variations from the canonical cortical column outline of layer 4 and core thalamocortical inputs were noted. In shrews/microchiropterans, layer 4 was present, but many core thalamocortical projections terminated in layer 1 in addition to layers 4 and inner 3. In primate primary visual cortex, the sublaminated layer 4 was associated with a specialized core thalamocortical projection pattern. In primate primary motor cortex, no cytoarchitecturally distinct layer 4 was evident and the core thalamocortical projections terminated throughout layer 3. In the African elephant, cetaceans, and river hippopotamus, no cytoarchitecturally distinct layer 4 was observed and core thalamocortical projections terminated primarily in inner layer 3 and less densely in outer layer 3. These findings are contextualized in terms of cortical processing, perception, and the evolutionary trajectory leading to an indistinct or absent cortical layer 4.en© 2024 The Author(s). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License.Cortical evolutionCortical layer IVCortical layersCortical processingRRID-AB_10000321RRID-AB_10000340RRID-AB_10000343RRID-AB_2187552RRID-AB_509997Skin–brain axisSDG-15: Life on landArticle