SPECIALTY GRAND CHALLENGE article

Front. Mamm. Sci., 13 June 2025

Sec. Nervous System and Cognate Behaviors

Volume 4 - 2025 | https://doi.org/10.3389/fmamm.2025.1603750

Grand challenge: finding similarities and differences in mammalian brain organization

  • 1. Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain

  • 2. Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Pozuelo de Alarcón, Madrid, Spain

Introduction

There are over 6,000 currently recognized species in the class Mammalia (). Biodiversity is the enduring result of past events and presents environmental and ecological conditions (). The ability to interact with the environment and display a range of behaviors depends on the coordinated interaction of different structures of the nervous system with specialized functions, from sensory receptors to higher sensory and motor processing centers. Thus, it is crucial to understand how these circuits operate in order to understand mammalian behavior.

Over the years, neuroscientists have been searching for organizational principles underlying mammalian brain function. From classical studies to advanced modern techniques, significant efforts have been made to understand the brain circuit organization. The first diagrams of brain circuits were created in the late 19th century, primarily by Cajal, using the Golgi method (reviewed in ). This technique allows for a detailed study of the morphology of neurons and their connections, marking a significant milestone in understanding brain architecture. Since then, the introduction of new methods and techniques has enabled researchers to progress the study of brain organization to better understand brain function and its role in cognition and behavior. Nowadays, big interdisciplinary international projects (e.g., Human Brain Project, Blue Brain Project, Brain Initiative, Human Connectome Project, Allen Institute Human Program, and The China Brain Project) are making use of advances in imaging, artificial intelligence, and computational neuroscience, with the aim of fully mapping brain connections. However, despite the outstanding progress made by these projects, the vast majority of neuroscientific studies in mammals have traditionally focused on investigating only a few species (mainly rodents and non-human primates). These species have primarily been chosen because of their suitability for standardized laboratory studies or their genomic similarities to humans (as with monkeys). Nevertheless, many mammals exhibit unique capabilities that have not yet been characterized in these species. Thus, one of the major challenges in mammalian neuroscience is to support the study of a broad range of species in order to reveal both conserved and species-specific features, ultimately leading to a better understanding of mammalian brains and their role in inducing behavior.

The importance of studying a broad range of species

Since the very early studies of brain organization, neuroscientists have been trying to understand how features such as brain size, the number of brain regions, cell lamination patterns, and interconnections between areas are organized in different brain regions, and how they relate to cognitive abilities. There has been a long-standing debate regarding the uniformity versus non-uniformity of brain organization, with some researchers emphasizing the similarities, while others highlight the differences (reviewed in ). For example, the cerebral cortex has been traditionally divided into a number of cytoarchitectonic fields that can be distinguished from their neighbors based on differences in the overall density, size, and shape of the cells and their arrangement in cortical layers, which supports the idea that differences in cortical organization would give rise to a distinct and specialized neural architecture (e.g., ; ; ; for a review, see ). Other researchers have proposed that functional differences between areas are mostly due to connections (; ; ; ). Supporters of this view affirm that during evolution, the complexity of the neocortex increased in larger brains due to the addition of microcircuits with the same basic structure. However, when a range of species other than those commonly used (mouse, rat, cat, monkey, and human) were considered, new arrangements were found (; ; ; ; ; ; ; ; ). Thus, new insights can be obtained by examining species diversity. For example, analyzing brains that are larger than the human brain can be of great interest, such as the brains of African elephants, in which it has been revealed that there are three times more neurons than in the average human brain; however, the majority of these neurons are found in the cerebellum, showing that it is the larger absolute number of neurons in the human cerebral cortex (but not in the whole brain), which correlates with the superior cognitive abilities of humans ().

Alternative methodologies have also allowed for the study of new aspects of circuitry, and comparative studies are becoming more common. Indeed, there is increasing evidence that each species has unique molecular, anatomical, and physiological features (; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ). In this regard, the concept of species-specific types of neurons is a matter of debate because the definition of a cell type depends on its morphological, physiological, molecular, and genetic composition (e.g., ). Consequently, it is important to examine the diversity of species from different perspectives and encourage anatomical, physiological, and molecular researchers to reach consensus on current controversial terms and issues (preferably by meeting in person) in order to clarify brain organization in different species (e.g., ; ; ; ; ).

Learning from the comparison of brain features

The study of different brains allows for the comparison of features across brain regions and species. If a particular brain microcircuit shows specific patterns responsible for information processing in a particular brain region, it can be investigated whether such patterns can serve as a foundation for comparing organizational principles across various brain systems, aiming to uncover both shared principles and region/species-specific adaptations (reviewed in ). Taking pyramidal cells (the basic building block of the cerebral cortex) as an example, it is possible to analyze the extent to which these cells have parallel morphologies in different cortical regions and species by comparing distinct anatomical features, which have important functional implications. Pyramidal cells are composed of distinct dendritic apical and basal compartments that receive and integrate information from functionally diverse areas (; ; ). These cells have been shown to be characterized—among different areas and species—by markedly different dendritic structures, which are directly related to function (reviewed in ; ). For example, certain areas of the prefrontal cortex of various primate species, including humans, have larger pyramidal cells, which are more branched and spinous than their counterparts in the occipital, parietal, and temporal lobes (; ; ; ; ). In addition, there is a trend towards increasing pyramidal cell complexity with anterior progression in the occipitotemporal cortex (reviewed in ). Regional variation in pyramidal cell structure has also been observed in mice, albeit to a lesser degree (; ). Briefly, the size of dendritic arbors influences their sampling geometry and the mixing of inputs; the patterns of dendritic branching may determine the degree to which the integration of inputs is compartmentalized within their arbors; and the density of dendritic spines influences various aspects related to the integration and co-operativity of inputs (e.g., ; ; ; ; ; ). Specifically, human pyramidal cells show greater, but not scalable, dendritic computation complexity in certain regions compared with pyramidal cells in other species, which accounts for the demonstrated singularity of the biophysics of these neurons (e.g., , ; ; ; ; ; ; ; , ; ; , , ; ; ; ). Nevertheless, there are relatively small and simple human pyramidal neurons, such as those in the visual cortex (; ). Interestingly, in brains that are larger than human brains—such as those of the African elephant—longer dendritic segments are found, but there is less intricate branching than that observed in human pyramidal cells. In addition, African elephants show regional variation similar to other rodent and primate species (; ).

Thus, through detailed analyses of the particular features of pyramidal neurons across regions and species, it is possible to find some common dendritic organizational patterns. Examples of such patterns that have so far been determined as conserved are as follows: pyramidal cell dendritic diameter values decrease as the branch order increases; the length of dendritic segments increases with higher branch orders; intermediate segments are thicker and shorter than terminal segments; terminal segments of pyramidal neurons exhibit similar widths; and the main apical dendritic diameter correlates with axonal diameter and soma size—whereas there are other features whose variation is found to contribute to the region/species-specificity, such as the dendritic diameter, number of primary dendrites, branching complexity, and spine density (; see also ; , ; ). Thus, some features reflect a general trend in the structural organization and design of pyramidal neurons, whereas other features represent specific morphological parameters that contribute to the existing diversity within pyramidal cell structures across different areas and species. In addition, by identifying the distinct and conserved features between regions and species, it is possible to hypothesize via which steps pyramidal cell complexity may have increased during cortical expansion: (1) an increase in dendritic diameter, followed by further dendritic width enhancement of apical main and basal dendrites, along with an increase in axonal diameter; and/or (2) an enlargement in neuron size, involving a) extension of distal dendritic segment lengths; b) increase in dendritic complexity (e.g., number of nodes and dendrites); and c) an increase in the number of dendritic spines ().

In addition, because morphological features highlight significant variations in the processing of information, it is possible to build models that demonstrate the biophysical and computational distinctiveness of neurons in different regions and species (e.g., , ). Furthermore, since the relationship between microscale cytoarchitecture and macroscale connectome organization has been established in several species, including humans (e.g., ; ; , ; ; ; ), the more elaborate the identification and extraction of the features of pyramidal neurons, the more comprehensive the characterization of macroscale organization. Therefore, it is essential to identify and extract features that capture the functional properties of pyramidal neurons in different cortical regions and species. Moreover, the study of the human brain in health and disease will not only help to better understand the mechanisms underlying human brain function but will also provide new insights into the underlying disease mechanisms of neurodegenerative and neurodevelopmental brain disorders.

Extrapolation of data matters: the case of the prefrontal cortex

A main concern regarding comparisons between species is the extrapolation of data between regions and species. The prefrontal cortex (PFC) is particularly relevant in this regard because its function is still poorly understood, and potential inter-species differences remain the subject of much debate, as demonstrated by a recent workshop that brought together experimental and computational scientists to discuss this matter (https://www.humanbrainproject.eu/en/education-training-career/workshops/pfc/). Here, we focus on only a few of the most pertinent points debated at this workshop. The granular prefrontal cortex (gPFC) is involved in a variety of high-level cognitive processes, particularly those involving executive control, attention, memory, and social behavior. It has undergone dramatic expansion in primates and is composed of diverse regions that vary in terms of the size, density, and distribution of their components, displaying a complex set of connections and diverse gene expression repertoire (reviewed in ; ; ; ; ; ). Nevertheless, the long-standing question alluded to above remains, that is, it has not yet been defined the extent to which it is possible to extrapolate from the whole PFC to specific regions of PFC, or species, to make comparisons (e.g., ). For example, rodents have homologs of the agranular areas found in primates but lack homologs of the granular cortex, which constitutes the largest part of the PFC in most primate species. Likewise, the connectivity observed in primates as a result or consequence of the new areas generated in primates cannot be studied in mice. Thus, it could be agreed that the delimitation of the PFC across species is based on the presence of a gPFC. Similarly, the overall homology of areas between species should be revised to define a more appropriate extrapolation of the data. Similarly, the extent to which the same behavioral task can be applied to different species should be better defined, highlighting potential limitations when comparing tasks across species. In particular, inferring from animal models to humans requires even more careful evaluation—not only due to species specificity, but also because there are technical and ethical constraints that limit the methods that can be used to study the human brain. Consequently, understanding the human brain requires the direct analysis whenever possible and there is a clear need for more strategic tools to achieve this. Similarly, it is important to outline the types of experiments or strategies that should be employed to examine each brain species. Finally, interindividual variability should also be considered, particularly in humans and the PFC region, which exhibits greater variability than that reported in other species (e.g., ; ; ).

Concluding remarks

In summary, it is essential to support the study of a broad range of species—rather than focusing solely on mice, rats, and other primates—to reveal the diversity of the animal kingdom. Identifying both conserved and species-specific features will help uncover the neural mechanisms underlying differing mammalian behaviors. The human brain has several unique features since every species has its own particular traits. Promoting research on the human brain is crucial to ensure a better understanding of its structure and function, which will ultimately help explain human behavior. Multidisciplinary approaches and collaboration between experimental and computational scientists are necessary to establish a consensus on the key issues related to brain organization across species.

Statements

Author contributions

RB: Writing – review & editing.

Funding

The author(s) declare that no financial support was received for the research and/or publication of this article.

Acknowledgments

I would like to thank Javier DeFelipe for insightful discussions and comments on earlier versions of this manuscript and Nick Guthrie for his helpful editorial assistance.

Conflict of interest

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

Publisher’s note

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References

  • 1

    AmuntsK.ZillesK. (2015). Architectonic mapping of the human brain beyond brodmann. Neuron88, 10861107. doi: 10.1016/j.neuron.2015.12.001

  • 2

    AndersonK.BonesB.RobinsonB.HassC.LeeH.FordK.et al. (2009). The morphology of supragranular pyramidal neurons in the human insular cortex: a quantitative Golgi study. Cereb Cortex.19, 21312144. doi: 10.1093/cercor/bhn234

  • 3

    AruJ.SuzukiM.LarkumM. E. (2020). Cellular mechanisms of conscious processing. Trends Cognit. Sci.24, 814825. doi: 10.1016/j.tics.2020.07.006

  • 4

    Ballesteros-YáñezI.Benavides-PiccioneR.BourgeoisJ.-P.ChangeuxJ.-P.DeFelipeJ. (2010). Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors. Proc. Natl. Acad. Sci. U S A107, 1156711572. doi: 10.1073/pnas.1006269107

  • 5

    BarbasH. (2015). General cortical and special prefrontal connections: principles from structure to function. Annu. Rev. Neurosci.38, 269289. doi: 10.1146/annurev-neuro-071714-033936

  • 6

    Beaulieu-LarocheL.TolozaE. H. S.van der GoesM. S.LafourcadeM.BarnagianD.WilliamsZ. M.et al. (2018). Enhanced dendritic compartmentalization in human cortical neurons. Cell175 (3), 643651.e14. doi: 10.1016/j.cell.2018.08.045

  • 7

    Benavides-PiccioneR.Blazquez-LlorcaL.KastanauskaiteA.Fernaud-EspinosaI.Tapia-GonzálezS.DeFelipeJ. (2024). Key morphological features of human pyramidal neurons. Cereb Cortex34, bhae180. doi: 10.1093/cercor/bhae180

  • 8

    Benavides-PiccioneR.Hamzei-SichaniF.Ballesteros-YáñezI.DeFelipeJ.YusteR. (2006). Dendritic size of pyramidal neurons differs among mouse cortical regions. Cereb Cortex16, 9901001. doi: 10.1093/cercor/bhj041

  • 9

    Benavides-PiccioneR.Regalado-ReyesM.Fernaud-EspinosaI.KastanauskaiteA.Tapia-GonzálezS.León-EspinosaG.et al. (2020). Differential structure of hippocampal CA1 pyramidal neurons in the human and mouse. Cereb Cortex30, 730752. doi: 10.1093/cercor/bhz122

  • 10

    Benavides-PiccioneR.RojoC.KastanauskaiteA.DeFelipeJ. (2021). Variation in pyramidal cell morphology across the human anterior temporal lobe. Cereb Cortex31, 35923609. doi: 10.1093/cercor/bhab034

  • 11

    BeulS. F.BarbasH.HilgetagC. C. (2017). A predictive structural model of the primate connectome. Sci. Rep.7, 43176. doi: 10.1038/srep43176

  • 12

    BianchiS.BauernfeindA. L.GuptaK.StimpsonC. D.SpocterM. A.BonarC. J.et al. (2011). Neocortical neuron morphology in Afrotheria: comparing the rock hyrax with the African elephant. Ann. N Y Acad. Sci.1225, 3746. doi: 10.1111/j.1749-6632.2011.05991.x

  • 13

    BrodmannK. (1909). Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues (Leipzig: Barth).

  • 14

    BurginC. J.ColellaJ. P.KahnP. L.UphamN. S. (2018). How many species of mammals are there? J. Mammalogy99, 114. doi: 10.1093/jmammal/gyx147

  • 15

    ChengetanaiS.TenleyJ. D.BertelsenM. F.HårdT.BhagwandinA.HaagensenM.et al. (2020). Brain of the African wild dog. I. Anatomy, architecture, and volumetrics. J. Comp. Neurol.528, 32453261. doi: 10.1002/cne.24999

  • 16

    CreutzfeldtO. D. (1977). Generality of the functional structure of the neocortex. Naturwissenschaften64, 507517. doi: 10.1007/BF00483547

  • 17

    DeFelipeJ. (2002). Cortical interneurons: from cajal to 2001. Prog. Brain Res.136, 215238. doi: 10.1016/s0079-6123(02)36019-9

  • 18

    DefelipeJ. (2011). The evolution of the brain, the human nature of cortical circuits, and intellectual creativity. Front. Neuroanat5. doi: 10.3389/fnana.2011.00029

  • 19

    DeFelipeJ.FariñasI. (1992). The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. Prog. Neurobiol.39, 563607. doi: 10.1016/0301-0082(92)90015-7

  • 20

    DeFelipeJ.López-CruzP. L.Benavides-PiccioneR.BielzaC.LarrañagaP.AndersonS.et al. (2013). New insights into the classification and nomenclature of cortical GABAergic interneurons. Nat. Rev. Neurosci.14, 202216. doi: 10.1038/nrn3444

  • 21

    de KockC. P. J.FeldmeyerD. (2023). Shared and divergent principles of synaptic transmission between cortical excitatory neurons in rodent and human brain. Front. Synaptic Neurosci.15. doi: 10.3389/fnsyn.2023.1274383

  • 22

    DouglasR. J.MartinK. A. C. (2004). Neuronal circuits of the neocortex. Annu. Rev. Neurosci.27, 419451. doi: 10.1146/annurev.neuro.27.070203.144152

  • 23

    EckerJ. R.GeschwindD. H.KriegsteinA. R.NgaiJ.OstenP.PolioudakisD.et al. (2017). The BRAIN initiative cell census consortium: lessons learned toward generating a comprehensive brain cell atlas. Neuron96, 542557. doi: 10.1016/j.neuron.2017.10.007

  • 24

    ElstonG. N. (2003). Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function. Cereb Cortex13, 11241138. doi: 10.1093/cercor/bhg093

  • 25

    ElstonG. N.Benavides-PiccioneR.DeFelipeJ. (2001). The pyramidal cell in cognition: a comparative study in human and monkey. J. Neurosci.21, RC163. doi: 10.1523/JNEUROSCI.21-17-j0002.2001

  • 26

    ElstonG. N.Benavides-PiccioneR.ElstonA.MangerP. R.DefelipeJ. (2011). Pyramidal cells in prefrontal cortex of primates: marked differences in neuronal structure among species. Front. Neuroanat5. doi: 10.3389/fnana.2011.00002

  • 27

    ElstonG. N.DeFelipeJ. (2002). Spine distribution in cortical pyramidal cells: a common organizational principle across species. Prog. Brain Res.136, 109133. doi: 10.1016/s0079-6123(02)36012-6

  • 28

    EyalG.VerhoogM. B.Testa-SilvaG.DeitcherY.Benavides-PiccioneR.DeFelipeJ.et al. (2018). Human cortical pyramidal neurons: from spines to spikes via models. Front. Cell Neurosci.12. doi: 10.3389/fncel.2018.00181

  • 29

    EyalG.VerhoogM. B.Testa-SilvaG.DeitcherY.LodderJ. C.Benavides-PiccioneR.et al. (2016). Unique membrane properties and enhanced signal processing in human neocortical neurons. Elife5, e16553. doi: 10.7554/eLife.16553

  • 30

    FusterJ. M. (2001). The prefrontal cortex–an update: time is of the essence. Neuron30, 319333. doi: 10.1016/s0896-6273(01)00285-9

  • 31

    GalakhovaA. A.HuntS.WilbersR.HeyerD. B.de KockC. P. J.MansvelderH. D.et al. (2022). Evolution of cortical neurons supporting human cognition. Trends Cognit. Sci.26, 909922. doi: 10.1016/j.tics.2022.08.012

  • 32

    García-CabezasM.ÁCheckt. a. e.ZikopoulosB.BarbasH. (2019). The Structural Model: a theory linking connections, plasticity, pathology, development and evolution of the cerebral cortex. Brain Struct. Funct.224, 9851008. doi: 10.1007/s00429-019-01841-9

  • 33

    GeschwindD. H.RakicP. (2013). Cortical evolution: judge the brain by its cover. Neuron. 80 (3), 633647. doi: 10.1016/j.neuron.2013.10.045

  • 34

    GidonA.ZolnikT. A.FidzinskiP.BolduanF.PapoutsiA.PoiraziP.et al. (2020). Dendritic action potentials and computation in human layer 2/3 cortical neurons. Science367, 8387. doi: 10.1126/science.aax6239

  • 35

    GlezerI. I.JacobsM. S.MorganeP. J. (1988). Implications of the “initial brain” concept for brain evolution in Cetacea. Behav. Brain Sci.11, 75116. doi: 10.1017/S0140525X0005281X

  • 36

    Goldman-RakicP. S. (1996). The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. Philos. Trans. R Soc. Lond B Biol. Sci.351, 14451453. doi: 10.1098/rstb.1996.0129

  • 37

    HaugH. (1987). Brain sizes, surfaces, and neuronal sizes of the cortex cerebri: a stereological investigation of man and his variability and a comparison with some mammals (primates, whales, marsupials, insectivores, and one elephant). Am. J. Anat180, 126142. doi: 10.1002/aja.1001800203

  • 38

    HawrylyczM. J.LeinE. S.Guillozet-BongaartsA. L.ShenE. H.NgL.MillerJ. A.et al. (2012). An anatomically comprehensive atlas of the adult human brain transcriptome. Nature489, 391399. doi: 10.1038/nature11405

  • 39

    Herculano-HouzelS.Avelino-de-SouzaK.NevesK.PorfírioJ.MessederD.Mattos FeijóL.et al. (2014). The elephant brain in numbers. Front. Neuroanat8. doi: 10.3389/fnana.2014.00046

  • 40

    HodgeR. D.BakkenT. E.MillerJ. A.SmithK. A.BarkanE. R.GraybuckL. T.et al. (2019). Conserved cell types with divergent features in human versus mouse cortex. Nature.573, 6168. doi: 10.1038/s41586-019-1506-7

  • 41

    HofP. R.GlezerI. I.NimchinskyE. A.ErwinJ. M. (2000). Neurochemical and cellular specializations in the mammalian neocortex reflect phylogenetic relationships: evidence from primates, cetaceans, and artiodactyls. Brain Behav. Evol.55, 300310. doi: 10.1159/000006665

  • 42

    HutslerJ. J.ZhangH. (2010). Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res.1309, 8394. doi: 10.1016/j.brainres.2009.09.120

  • 43

    JacobsB.ScheibelA. B. (1993). A quantitative dendritic analysis of Wernicke’s area in humans. I. Lifespan changes. J. Comp. Neurol.327, 8396. doi: 10.1002/cne.903270107

  • 44

    JacobsB.DriscollL.SchallM. (1997). Life-span dendritic and spine changes in areas 10 and 18 of human cortex: a quantitative Golgi study. J. Comp. Neurol.386, 661680. doi: 10.1002/(SICI)1096-9861(19971006)386:4<661::AID-CNE11>3.0.CO;2-N

  • 45

    JacobsB.LubsJ.HannanM.AndersonK.ButtiC.SherwoodC. C.et al. (2011). Neuronal morphology in the African elephant (Loxodonta africana) neocortex. Brain Struct. Funct.215, 273298. doi: 10.1007/s00429-010-0288-3

  • 46

    JacobsB.SchallM.PratherM.KaplerE.DriscollL.BacaS.et al. (2001). Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study. Cereb Cortex11, 558571. doi: 10.1093/cercor/11.6.558

  • 47

    JacobsB.ScheibelA. B. (2002). Regional dendritic variation in primate cortical pyramidal cells. Cortical Areas: Unity and DiversitySchüzA.MillerR.. London: Taylor & Francis, 111131.

  • 48

    JonesK. E.SafiK. (2011). Ecology and evolution of mammalian biodiversity. Philos. Trans. R Soc. Lond B Biol. Sci.366, 24512461. doi: 10.1098/rstb.2011.0090

  • 49

    KaasJ. H. (2013). The evolution of brains from early mammals to humans. Wiley Interdiscip Rev. Cognit. Sci.4, 3345. doi: 10.1002/wcs.1206

  • 50

    KalmbachB. E.HodgeR. D.JorstadN. L.OwenS.de FratesR.YannyA. M.et al. (2021). Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons. Neuron109, 29142927.e5. doi: 10.1016/j.neuron.2021.08.030

  • 51

    KanariL.ShiY.ArnaudonA.Barros-ZulaicaN.Benavides-PiccioneR.CogganJ. S.et al. (2024). Of mice and men: Dendritic architecture differentiates human from mice neuronal networks. bioRxiv18, 2023.09.11.557170. doi: 10.1101/2023.09.11.557170

  • 52

    KochC.PoggioT.TorreV. (1982). Retinal ganglion cells: a functionalinterpretation of dendritic morphology. Phil Trans. R Soc. Lond Ser. B.298, 227264. doi: 10.1098/rstb.1982.0084

  • 53

    KolkS. M.RakicP. (2022). Development of prefrontal cortex. Neuropsychopharmacology47, 4157. doi: 10.1038/s41386-021-01137-9

  • 54

    LeeB. R.DalleyR.MillerJ. A.ChartrandT.CloseJ.MannR.et al. (2023). Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex. Science382, eadf6484. doi: 10.1126/science.adf6484

  • 55

    LondonM.HäusserM. (2005). Dendritic computation. Annu. Rev. Neurosci.28, 503532. doi: 10.1146/annurev.neuro.28.061604.135703

  • 56

    LuebkeJ. I. (2017). Pyramidal neurons are not generalizable building blocks of cortical networks. Front. Neuroanat11. doi: 10.3389/fnana.2017.00011

  • 57

    LundJ. S.YoshiokaT.LevittJ. B. (1993). Comparison of intrinsic connectivity in different areas of macaque monkey cerebral cortex. Cereb Cortex3, 148162. doi: 10.1093/cercor/3.2.148

  • 58

    LuriaV.MaS.ShibataM.PattabiramanK.SestanN. (2023). Molecular and cellular mechanisms of human cortical connectivity. Curr. Opin. Neurobiol.80, 102699. doi: 10.1016/j.conb.2023.102699

  • 59

    MalachR. (1994). Cortical columns asdevices for maximizing neuronal diversity. Trends Neurosci.17, 101104. doi: 10.1016/0166-2236(94)90113-9

  • 60

    MangerP. R.PatzkeN.SpocterM. A.BhagwandinA.KarlssonK.Æ.BertelsenM. F.et al. (2021). Amplification of potential thermogenetic mechanisms in cetacean brains compared to artiodactyl brains. Sci. Rep.11, 5486. doi: 10.1038/s41598-021-84762-0

  • 61

    MarchettoM. C.Hrvoj-MihicB.KermanB. E.YuD. X.VadodariaK. C.LinkerS. B.et al. (2019). Species-specific maturation profiles of human, chimpanzee and bonobo neural cells. Elife.8, e37527. doi: 10.7554/eLife.37527

  • 62

    MasoliS.Sanchez-PonceD.VrielerN.Abu-HayaK.LernerV.ShaharT.et al. (2024). Human Purkinje cells outperform mouse Purkinje cells in dendritic complexity and computational capacity. Commun. Biol.7, 118. doi: 10.1038/s42003-023-05689-y

  • 63

    MertensE. J.LeibnerY.PieJ.GalakhovaA. A.WaleboerF.MeijerJ.et al. (2024). Morpho-electric diversity of human hippocampal CA1 pyramidal neurons. Cell Rep.43, 114100. doi: 10.1016/j.celrep.2024.114100

  • 64

    MolnárZ.ClowryG. J.ŠestanN.Alzu’biA.BakkenT.HevnerR. F.et al. (2019). New insights into the development of the human cerebral cortex. J. Anat.235, 432451. doi: 10.1111/joa.13055

  • 65

    NelsonS. (2002). Cortical microcircuits: diverse or canonical? Neuron36, 1927. doi: 10.1016/s0896-6273(02)00944-3

  • 66

    OberheimN. A.TakanoT.HanX.HeW.LinJ. H.WangF.et al. (2009). Uniquely hominid features of adult human astrocytes. J. Neurosci.29, 32763287. doi: 10.1523/JNEUROSCI.4707-08.2009

  • 67

    PengY.MittermaierF. X.PlanertH.SchneiderU. C.AlleH.GeigerJ. R. P. (2019). High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp. Elife8, e48178. doi: 10.7554/eLife.48178

  • 68

    Petilla Interneuron Nomenclature GroupAscoliG. A.Alonso-NanclaresL.AndersonS. A.BarrionuevoG.Benavides-PiccioneR.et al. (2008). Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci.9, 557568. doi: 10.1038/nrn2402

  • 69

    PreussT. M. (1995). Do rats have prefrontal cortex? The rose-woolsey-akert program reconsidered. J. Cognit. Neurosci.7, 124. doi: 10.1162/jocn.1995.7.1.1

  • 70

    PreussT. M.ColemanG. Q. (2002). Human-specific organization of primary visual cortex: alternating compartments of dense Cat-301 and calbindin immunoreactivity in layer 4A. Cereb Cortex12, 671691. doi: 10.1093/cercor/12.7.671

  • 71

    PreussT. M.WiseS. P. (2022). Evolution of prefrontal cortex. Neuropsychopharmacol.47, 319. doi: 10.1038/s41386-021-01076-5

  • 72

    ReepR. L.JohnsonJ. I.SwitzerR. C.WelkerW. I. (1989). Manatee cerebral cortex: cytoarchitecture of the frontal region in Trichechus manatus latirostris. Brain Behav. Evol.34, 365386. doi: 10.1159/000116523

  • 73

    RockelA. J.HiornsR. W.PowellT. P. (1980). The basic uniformity in structure of the neocortex. Brain103, 221244. doi: 10.1093/brain/103.2.221

  • 74

    ScholtensL. H.SchmidtR.de ReusM. A.van den HeuvelM. P. (2014). Linking macroscale graph analytical organization to microscale neuroarchitectonics in the macaque connectome. J. Neurosci.34, 1219212205. doi: 10.1523/JNEUROSCI.0752-14.2014

  • 75

    ShepherdG. M.BraytonR. K.MillerJ. P.SegevI.RinzelJ.RallW. (1985). Signal enhancement in distal cortical dendrites by means of interactions between active dendritic spines. Proc. Natl. Acad. Sci. U S A82, 21922195. doi: 10.1073/pnas.82.7.2192

  • 76

    ShepherdG. M.GrillnerS. (2010). Handbook of brain microcircuits (Oxford: Oxford: Oxford University Press).

  • 77

    SherwoodC. C.BauernfeindA. L.BianchiS.RaghantiM. A.HofP. R. (2012). Human brain evolution writ large and small. Prog Brain Res. 195, 237254. doi: 10.1016/B978-0-444-53860-4.00011-8

  • 78

    SousaA. M. M.MeyerK. A.SantpereG.GuldenF. O.SestanN. (2017). Evolution of the human nervous system function, structure, and development. Cell170, 226247. doi: 10.1016/j.cell.2017.06.036

  • 79

    SprustonN. (2008). Pyramidal neurons: dendritic structure and synaptic integration. Nat. Rev. Neurosci.9, 206221. doi: 10.1038/nrn2286

  • 80

    StolzenburgJ. U.ReichenbachA.NeumannM. (1989). Size and density of glial and neuronal cells within the cerebral neocortex of various insectivorian species. Glia2, 7884. doi: 10.1002/glia.440020203

  • 81

    SzentágothaiJ. (1978). The Ferrier Lecture 1977. The neuron network of the cerebral cortex: a functional interpretation. Proc. R Soc. Lond B Biol. Sci.201, 219248. doi: 10.1098/rspb.1978.0043

  • 82

    van den HeuvelM. P.ScholtensL. H.de ReusM. A.KahnR. S. (2016). Associated microscale spine density and macroscale connectivity disruptions in schizophrenia. Biol. Psychiatry80, 293301. doi: 10.1016/j.biopsych.2015.10.005

  • 83

    van den HeuvelM. P.ScholtensL. H.Feldman BarrettL.HilgetagC. C.de ReusM. A. (2015). Bridging cytoarchitectonics and connectomics in human cerebral cortex. J. Neurosci.35, 1394313948. doi: 10.1523/JNEUROSCI.2630-15.2015

  • 84

    VerendeevA.SherwoodC. C. (2017). Human brain evolution. Curr. Opin. Behav. Sci.16, 4145. doi: 10.1016/j.cobeha.2017.02.003

  • 85

    von EconomoC. F.KoskinasG. N. (1925). Die cytoarchitektonik derhirnrinde des erwachsenen menschen. (Berlin: Springer). Available online at: https://books.google.es/books?id=2DVBAAAAYAAJ.

  • 86

    von EconomoC. (1927). Zellaufbau der Grosshirnrinde des Menschen. (Berlin: Springer).

  • 87

    WeiY.ScholtensL. H.TurkE.van den HeuvelM. P. (2019). Multiscale examination of cytoarchitectonic similarity and human brain connectivity. Netw Neurosci.3, 124137. doi: 10.1162/netn_a_00057

  • 88

    YusteR.HawrylyczM.AallingN.Aguilar-VallesA.ArendtD.ArmañanzasR.et al. (2020). A community-based transcriptomics classification and nomenclature of neocortical cell types. Nat. Neurosci.23, 14561468. doi: 10.1038/s41593-020-0685-8

  • 89

    ZebaM.Jovanov-MilosevićN.PetanjekZ. (2008). Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex. Coll. Antropol.32 Suppl 1, 161169.

Summary

Keywords

comparative neuroanatomy, structure, species-specific, specializations, conserved

Citation

Benavides-Piccione R (2025) Grand challenge: finding similarities and differences in mammalian brain organization. Front. Mamm. Sci. 4:1603750. doi: 10.3389/fmamm.2025.1603750

Received

31 March 2025

Accepted

09 May 2025

Published

13 June 2025

Volume

4 - 2025

Edited and reviewed by

Paul Manger, University of the Witwatersrand, South Africa

Updates

Copyright

*Correspondence: Ruth Benavides-Piccione,

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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