Can We Explain Thousands of Molecularly Identified Mouse Neuronal Types? From Knowing to Understanding.

At the end of 2023, the Whole Mouse Brain Atlas was announced, revealing that there are about 5300 molecularly defined neuronal types in the mouse brain. We ask whether brain models exist that contemplate how this is possible. The conventional columnar model, implicitly used by the authors of the Atlas, is incapable of doing so with only 20 brain columns (5 brain vesicles with 4 columns each). We argue that the definition of some 1250 distinct progenitor microzones, each producing at least 4-5 neuronal types over time, may be sufficient. Presently, this is nearly achieved by the prosomeric model amplified by the secondary dorsoventral and anteroposterior microzonation of progenitor areas, plus the clonal variation in cell types produced, on average, by each of them.

A new 3D myeloarchitectonic map of the human neocortex based on data from the Vogt-Vogt school.

During the period extending from 1900 to 1970, Oskar and Cécile Vogt and their numerous collaborators ('the Vogt-Vogt school') published a large number of studies on the myeloarchitecture of the human cerebral cortex. During the last decade, we have concerned ourselves with a detailed meta-analysis of these now almost totally forgotten studies, with the aim to bringing them into the modern era of science. This scrutiny yielded inter alia a myeloarchitectonic map of the human neocortex, showing a parcellation into 182 areas (Nieuwenhuys et al. in Brain Struct Funct 220:2551-2573, 2015; Erratum in Brain Struct Funct 220: 3753-3755, 2015). This map, termed 2D'15, which is based on data derived from all of the 20 publications constituting the myeloarchitectonic legacy of the Vogt-Vogt school, has the limitation that it is two-dimensional i.e. it shows only the parts of the cortex exposed at the free surface of the cerebral hemispheres and not the extensive stretches of cortex hidden in the cortical sulci. However, a limited set of data, derived from four of the 20 publications available, has enabled us to create a 3D map, showing the myeloarchitectonic parcellation of the entire human neocortex. This map, designated as 3D'23, contains 182 areas: 64 frontal, 30 parietal, 6 insular, 19 occipital and 63 temporal. We have also prepared a 2D version (2D'23), of this 3D'23 map to serve as a link between the latter and our original 2D'15 map. Detailed comparison of the parcellations visualized in our three maps (2D'15, 2D'23 and 3D'23) warrants the conclusion that our new 3D'23 map may be considered as representative for the entire myeloarchitectural legacy of the Vogt-Vogt School. Hence it is now possible to compare the rich amount of myeloarchitectonic data assembled by that school directly with the results of current 3D analyses of the architecture of the human cortex, such as the meticulous quantitative cyto- and receptor architectonic studies of Zilles, Amunts and their numerous associates (Amunts et al. in Science 369:988-992, 2020), and the multimodal parcellation of the human cortex based on magnetic resonance images from the Human Connectome Project, performed by Glasser et al. in Nature 536:171-178, 2016).

Topological Analysis of the Brainstem of the Australian Lungfish Neoceratodus forsteri.

This paper presents a survey of the cell masses in the brainstem of the Australian lungfish Neoceratodus forsteri, based ontransversely cut Bodian-stained serial sections, supplemented by immunohistochemical data from the recent literature. This study is intended to serve a double purpose. First it concludes and completes a series of publications on the structure of the brainstem in representative species of all groups of anamniote vertebrates. Within the framework of this comparative program the cell masses in the brainstem and their positional relations are analyzed in the light of the Herrick-Johnston concept, according to which the brainstem nuclei are arranged in four longitudinal, functional zones or columns, the boundaries of which are marked by ventricular sulci. The procedure employed in this analysis essentially involves two steps: first, the cell masses and large individual cells are projected upon the ventricular surface, and next, the ventricular surface is flattened out, that is, subjected to a one-to-one continuous topological transformation [J Comp Neurol. 1974;156:255-267]. The second purpose of the present paper is to complement our mapping of the longitudinal zonal arrangement of the cell masses in the brainstem of Neoceratoduswith a subdivision in transversely oriented neural segments. Five longitudinal rhombencephalic sulci - the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, the sulcus intermedius dorsalis and the sulcus medianus superior - and four longitudinal mesencephalic sulci - the sulcus tegmentalis medialis, the sulcus tegmentalis lateralis, the sulcus subtectalis and the sulcus lateralis mesencephali - could be distinguished. Two obliquely oriented grooves, present in the isthmic region - the sulcus isthmi dorsalis and ventralis - deviate from the overall longitudinal pattern of the other sulci. Although in Neoceratodus most neuronal perikarya are situated within a diffuse periventricular gray, 45 cell masses could be delineated. Ten of these are primary efferent or motor nuclei, eight are primary afferent or sensory centers, six are considered to be components of the reticular formation and the remaining 21 may be interpreted as "relay" nuclei. The topological analysis showed that in most of the rhombencephalon the gray matter is arranged in four longitudinal zones or areas, termed area ventralis, area intermedioventralis, area intermediodorsalis and area dorsalis. The sulcus intermedius ventralis, the sulcus limitans, and the sulcus intermedius dorsalis mark the boundaries between these morphological entities. These longitudinal zones coincide largely, but not entirely, with the functional columns of Herrick and Johnston. The most obvious incongruity is that the area intermediodorsalis contains, in addition to the viscerosensory nucleus of the solitary tract, several general somatosensory and special somatosensory centers. The isthmus region does not exhibit a clear morphological zonal pattern. The mesencephalon is divisible into a ventral, primarily motor zone and a dorsal somatosensory zone. The boundary between these zones is marked by the sulcus tegmentalis lateralis, which may be considered as an isolated rostral extremity of the sulcus limitans. The results of this study are summarized in a "classical" topological map, as well as in a "modernized" version of this map, in which neuromere borders are indicated.

A detailed comparison of the cytoarchitectonic and myeloarchitectonic maps of the human neocortex produced by the Vogt-Vogt school.

The comprehensive research programme of the Vogt-Vogt (V-V) school, which was active during the period 1900-1970, included detailed cytoarchitectonic and myeloarchitectonic analyses of the human cerebral cortex, with the aim to integrate the data obtained into a map, showing a parcellation of the human cerebral cortex into fundamental structural and potentially functional units. The cytoarchitectonic V-V analyses yielded two maps of the human cerebral cortex, the famous map of Brodmann (Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Barth, Leipzig, 1909), Brodmann (in: Bruns P (ed) Neue deutsche Chirurgie, Enke, Stuttgart, 1914), and the less known, but more detailed map of Sarkisov et al. (Cytoarchitecture of the human cortex cerebri. Medgiz, Moscow, 1949). Sarkisov et al. used in their cytoarchitectonic parcellation of the cortex the same numbering scheme as Brodmann. They confirmed the presence of most of the areas delineated by the latter, but they subdivided several of these areas into two or more separate areas or subareas. Within the realm of the myeloarchitectonic V-V analyses, numerous meticulous studies of the cortex of individual cerebral lobes were carried out, but these were not united into a single map. Consequently, the envisioned integration of cytoarchitectonic and myeloarchitectonic data mentioned above was never realized. Some years ago, we (Nieuwenhuys et al. in Brain Struct Funct 220:2551-2573, 2015a, Nieuwenhuys et al. in Brain Struct Funct 220:3753-3755, 2015b) reanalyzed the V-V myeloarchitectonic data, and succeeded in constructing a complete myeloarchitectonic map of the human neocortex from these data. Because the data provided by the V-V school were derived from many different brains, a standard brain had to be introduced as a template to which all data available could be transferred. As such the MNI305 template was selected. Having made available now the cytoarchitectonic maps of Brodmann and Sarkisov et al. and the recently prepared myeloarchitectonic map, an attempt is made here to realize at last the original aim of the V-V school, viz. the preparation of a single, combined (cyto + myelo) architectonic map of the human cortex. To this end, the following three steps have been made. First, Brodmann's (BR) map, and the map of Sarkisov et al. (SA) were harmoniously transferred to the same template brain as the one used during the construction of our myeloarchitectonic map. Second, the standardized BR and our myeloarchitectonic (NI) map were compared, and the data contained within these maps were integrated into a single standardized combined BR-NI map (Fig. 11). The standardized SA and NI maps were subjected to the same procedure (Fig. 12). Finally, the standardized combined BR-NI and SA-NI maps were united into a single combined BR-SA-NI map (Fig. 13). This map renders it possible to make direct comparisons between the results of the architectonic studies of the V-V school and current parcellations of the human neocortex.

The segmentation of the human brain; a message to the neuroimaging community from an adjacent domain of the neurosciences.

Morphological and genoarchitectonic studies have conclusively shown that the human brain (and that of all vertebrates) is segmented i. e. is fundamentally composed of a number of rostrocaudally arranged brain segments or neuromeres. However in the current neuroimaging literature the term segmentation, derived initially from computer graphics technology, is used instead to indicate the neuroanatomical parcellation or subdivision of neural structures in the fully formed brain, especially the cortex. The neuroimaging community should be aware of the prior use of this term in the parallel discipline of neuroembryology, and should use a different one e.g. parcellation to avoid any confusion between the two growing disciplines.

Principles of Current Vertebrate Neuromorphology.

Causal analysis of molecular patterning at neural plate and early neural tube stages has shown that the central nervous system (CNS) of vertebrates is essentially organized into transverse neural segments or neuromeres and longitudinal zones which follow the curved axis of the brain. The intersection of the longitudinal and transverse patterning processes in the embryonic brain leads to the formation of a checkerboard pattern of distinct progenitor domains called "fundamental morphological units" (FMUs). The topologically invariant pattern formed by the ventricular surfaces of the FMUs of a given taxon represents the "Bauplan" or "blueprint" of the brain of that taxon. The FMUs initially represent thin epithelial fields; during further development they are transformed into three-dimensional radial units, extending from the ventricular surface to the meningeal surface. It is of note that the boundaries of the neuromeres, longitudinal zones, and radial units all strictly adhere to a non-Cartesian coordinate system inherent to the CNS of all vertebrates. The major neural histogenetic processes, including cellular proliferation, radial migration, and differentiation, as well as the formation of grisea (cell masses, nuclei, and cortices), occur principally within the confines of the FMUs, although tangential migration may also take cells to distant sites. Hence, recognition and delimitation of these units is essential for the identification and interpretation of grisea. An outline of the procedure to be followed in these processes of identification and interpretation is presented, and a list of the pertinent homology criteria is provided.

A map of the human neocortex showing the estimated overall myelin content of the individual architectonic areas based on the studies of Adolf Hopf.

During the period extending from 1910 to 1970, Oscar and Cécile Vogt and their numerous collaborators published a large number of myeloarchitectonic studies on the cortex of the various lobes of the human cerebrum. In a previous publication [Nieuwenhuys et al (Brain Struct Funct 220:2551-2573, 2015; Erratum in Brain Struct Funct 220: 3753-3755, 2015)], we used the data provided by the Vogt-Vogt school for the composition of a myeloarchitectonic map of the entire human neocortex. Because these data were derived from many different brains, a standard brain had to be introduced to which all data available could be transferred. As such the Colin 27 structural scan, aligned to the MNI305 template was selected. The resultant map includes 180 myeloarchitectonic areas, 64 frontal, 30 parietal, 6 insular, 17 occipital and 63 temporal. Here we present a supplementary map in which the overall density of the myelinated fibers in the individual architectonic areas is indicated, based on a meta-analysis of data provided by Adolf Hopf, a prominent collaborator of the Vogts. This map shows that the primary sensory and motor regions are densely myelinated and that, in general, myelination decreases stepwise with the distance from these primary regions. The map also reveals the presence of a number of heavily myelinated formations, situated beyond the primary sensory and motor domains, each consisting of two or more myeloarchitectonic areas. These formations were provisionally designated as the orbitofrontal, intraparietal, posterolateral temporal, and basal temporal dark clusters. Recently published MRI-based in vivo myelin content mappings show, with regard to the primary sensory and motor regions, a striking concordance with our map. As regards the heavily myelinated clusters shown by our map, scrutiny of the current literature revealed that correlates of all of these clusters have been identified in in vivo structural MRI studies and appear to correspond either entirely or largely to known cytoarchitectonic entities. Moreover, functional neuroimaging studies indicate that all of these clusters are involved in vision-related cognitive functions.

A new myeloarchitectonic map of the human neocortex based on data from the Vogt-Vogt school.

The human cerebral cortex contains numerous myelinated fibres, the arrangement and density of which is by no means homogeneous throughout the cortex. Local differences in the spatial organization of these fibres render it possible to recognize areas with a different myeloarchitecture. The neuroanatomical subdiscipline aimed at the identification and delineation of such areas is known as myeloarchitectonics. During the period extending from 1910 to 1970, Oscar and Cécile Vogt and their numerous collaborators (The Vogt-Vogt school) published a large number of myeloarchitectonic studies on the cortex of the various lobes of the human cerebrum. Recently, one of us (Nieuwenhuys in Brain Struct Funct 218: 303-352, 2013) extensively reviewed these studies. It was concluded that the data available are adequate and sufficient for the composition of a myeloarchitectonic map of the entire human neocortex. The present paper is devoted to the creation of this map. Because the data provided by the Vogt-Vogt school are derived from many different brains, a standard brain had to be introduced to which all data available could be transferred. As such, the colin27 structural scan, aligned to the MNI305 template was selected. The procedure employed in this transfer involved computer-aided transformations of the lobar maps available in the literature, to the corresponding regions of the standard brain, as well as local adjustments in the border zones of the various lobes. The resultant map includes 180 myeloarchitectonic areas, 64 frontal, 30 parietal, 6 insular, 17 occipital and 63 temporal. The designation of the various areas with simple Arabic numbers, introduced by Oscar Vogt for the frontal and parietal cortices, has been extended over the entire neocortex. It may be expected that combination of the myeloarchitectonic data of the Vogt-Vogt school, as expressed in our map, with the results of the detailed cytoarchitectonic and receptor architectonic studies of Karl Zilles and Katrin Amunts and their numerous associates, will yield a comprehensive 'supermap' of the structural organization of the human neocortex. For the time being, i. e., as long as this 'supermap' is not yet available, our map may provide a tentative frame of reference for (a) the morphological interpretation of the results of functional neuroimaging studies; (b) the selection of starting points (seed voxels, regions-of-interest) in diffusion tractography studies and

The myeloarchitectonic studies on the human cerebral cortex of the Vogt-Vogt school, and their significance for the interpretation of functional neuroimaging data.

The human cerebral cortex contains numerous myelinated fibres, many of which are concentrated in tangentially organized layers and radially oriented bundles. The spatial organization of these fibres is by no means homogeneous throughout the cortex. Local differences in the thickness and compactness of the fibre layers, and in the length and strength of the radial bundles renders it possible to recognize areas with a different myeloarchitecture. The neuroanatomical subdiscipline aimed at the identification and delineation of such areas is known as myeloarchitectonics. There is another, closely related neuroanatomical subdiscipline, named cytoarchitectonics. The aims and scope of this subdiscipline are the same as those of myeloarchitectonics, viz. parcellation. However, this subdiscipline focuses, as its name implies, on the size, shape and arrangement of the neuronal cell bodies in the cortex, rather than on the myelinated fibres. At the beginning of the twentieth century, two young investigators, Oskar and Cécile Vogt founded a centre for brain research, aimed to be devoted to the study of the (cyto + myelo) architecture of the cerebral cortex. The study of the cytoarchitecture was entrusted to their collaborator Korbinian Brodmann, who gained great fame with the creation of a cytoarchitectonic map of the human cerebral cortex. Here, we focus on the myeloarchitectonic studies on the cerebral cortex of the Vogt-Vogt school, because these studies are nearly forgotten in the present attempts to localize functional activations and to interprete findings in modern neuroimaging studies. Following introductory sections on the principles of myeloarchitectonics, and on the achievements of three myeloarchitectonic pioneers who did not belong to the Vogt-Vogt school, the pertinent literature is reviewed in some detail. These studies allow the conclusion that the human neocortex contains about 185 myeloarchitectonic areas, 70 frontal, 6 insular, 30 parietal, 19 occipital, and 60 temporal. It is emphasized that the data available, render it possible to compose a myeloarchitectonic map of the human neocortex, which is at least as reliable as any of the classic architectonic maps. During the realization of their myeloarchitectonic research program, in which numerous able collaborators were involved, the Vogts gradually developed a general concept of the organization of the cerebral cortex. The essence of this concept is that this structure is composed of about 200 distinct, juxtaposed 'Rindenfelder' or 'topistische Einheiten', which represent fundamental structural as well as functional entities. The second main part of this article is devoted to a discussion and evaluation of this 'Vogt-Vogt concept'. It is concluded that there is converging quantitative cytoarchitectonic, receptor architectonic, myeloarchitectonic, hodological, and functional evidence, indicating that this concept is essentially correct. The third, and final part of this article deals with the problem of relating particular cortical functions, as determined with neuroimaging techniques, to particular cortical structures. At present, these 'translation' operations are generally based on adapted, three-dimensional versions of Brodmann's famous map. However, it has become increasingly clear that these maps do not provide the neuroanatomical precision to match the considerable degree of functional segregation, suggested by neuroimaging studies. Therefore, we strongly recommend an attempt at combining and synthesizing the results of Brodmann's cytoarchitectonic analysis, with those of the detailed myeloarchitectonic studies of the Vogt-Vogt school. These studies may also be of interest for the interpretation of the myeloarchitectonic features, visualized in modern in vivo mappings of the human cortex.

The insular cortex: a review.

The human insular cortex forms a distinct, but entirely hidden lobe, situated in the depth of the Sylvian fissure. Here, we first review the recent literature on the connectivity and the functions of this structure. It appears that this small lobe, taking up less than 2% of the total cortical surface area, receives afferents from some sensory thalamic nuclei, is (mostly reciprocally) connected with the amygdala and with many limbic and association cortical areas, and is implicated in an astonishingly large number of widely different functions, ranging from pain perception and speech production to the processing of social emotions. Next, we embark on a long, adventurous journey through the voluminous literature on the structural organization of the insular cortex. This journey yielded the following take-home messages: (1) The meticulous, but mostly neglected publications of Rose (1928) and Brockhaus (1940) are still invaluable for our understanding of the architecture of the mammalian insular cortex. (2) The relation of the insular cortex to the adjacent claustrum is neither ontogenetical nor functional, but purely topographical. (3) The insular cortex has passed through a spectacular progressive differentiation during hominoid evolution, but the assumption of Craig (2009) that the human anterior insula has no homologue in the rhesus monkey is untenable. (4) The concept of Mesulam and Mufson (1985), that the primate insula is essentially composed of three concentrically arranged zones, agranular, dysgranular, and granular, is presumably correct, but there is at present much confusion concerning the more detailed architecture of the anterior insular cortex. (5) The large spindle-shaped cells in the fifth layer of the insular cortex, currently known as von Economo neurons (VENs), are not only confined to large-brained mammals, such as whales, elephants, apes, and humans, but also occur in monkeys and prosimians, as well as in the pygmy hippopotamus, the Atlantic walrus, and Florida manatee. Finally, we point out that the human insula presents a unique opportunity for performing an in-depth comparative analysis of the relations between structure and function in a typical sensory and a typical cognitive cortical domain.

The structural, functional, and molecular organization of the brainstem.

According to His (1891, 1893) the brainstem consists of two longitudinal zones, the dorsal alar plate (sensory in nature) and the ventral basal plate (motor in nature). Johnston and Herrick indicated that both plates can be subdivided into separate somatic and visceral zones, distinguishing somatosensory and viscerosensory zones within the alar plate, and visceromotor and somatomotor zones within the basal plate. To test the validity of this "four-functional-zones" concept, I developed a topological procedure, surveying the spatial relationships of the various cell masses in the brainstem in a single figure. Brainstems of 16 different anamniote species were analyzed, and revealed that the brainstems are clearly divisible into four morphological zones, which correspond largely with the functional zones of Johnston and Herrick. Exceptions include (1) the magnocellular vestibular nucleus situated in the viscerosensory zone; (2) the basal plate containing a number of evidently non-motor centers (superior and inferior olives). Nevertheless the "functional zonal model" has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioral profiles, as "local hypertrophies" of one or two functional columns. Recent developmental molecular studies on brains of birds and mammals confirmed the presence of longitudinal zones, and also showed molecularly defined transverse bands or neuromeres throughout development. The intersecting boundaries of the longitudinal zones and the transverse bands appeared to delimit radially arranged histogenetic domains. Because neuromeres have been observed in embryonic and larval stages of numerous anamniote species, it may be hypothesized that the brainstems of all vertebrates share a basic organizational plan, in which intersecting longitudinal and transverse zones form fundamental histogenetic and genoarchitectonic units.

The development and general morphology of the telencephalon of actinopterygian fishes: synopsis, documentation and commentary.

The Actinopterygii or ray-finned fishes comprise, in addition to the large superorder of teleosts, four other superorders, namely the cladistians, the chondrosteans, the ginglymodes, and the halecomorphs, each with a limited number of species. The telencephalon of actinopterygian fishes differs from that in all other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. At the end of the nineteenth century, the theory was advanced that the unusual configuration of the forebrain in actinopterygians results from an outward bending or eversion of its lateral walls. This theory was accepted by some authors, rejected or neglected by others, and modified by some other authors. The present paper is based on the data derived from the literature, complemented by new observations on a large collection of histological material comprising specimens of all five actinopterygian superorders. The paper consists of three parts. In the first, a survey of the development of the telencephalon in actinopterygian fishes is presented. The data collected show clearly that an outward bending or eversion of the pallial parts of the solid hemispheres is the principal morphogenetic event in all five actinopterygian superorders. In all of these superorders, except for the cladistians, eversion is coupled with a marked thickening of the pallial walls. In the second part, some aspects of the general morphology of the telencephalon in mature actinopterygians are highlighted. It is pointed out that (1) the degree of eversion varies considerably among the various actinopterygian groups; (2) eversion leads to the transformation of the telencephalic roof plate into a wide membrane or tela choroidea, which is bilaterally attached to the lateral or ventrolateral aspect of the solid hemispheres; (3) the lines of attachment or taeniae of the tela choroidea form the most important landmarks in the telencephalon of actinopterygians, indicating the sites where the greatly enlarged ventricular surface of the hemispheres ends and its reduced meningeal surface begins; (4) the meningeal surface of the telencephalon shows in most actinopterygians bilaterally a longitudinally oriented sulcus externus, the depth of which is generally positively correlated with the degree of eversion; (5) a distinct lateral olfactory tract, occupying a constant topological position close to the taenia, is present in all actinopterygians studied; and (6) this tract is not homologous to the tract of the same name in the evaginated and inverted forebrains of other groups of vertebrates. In the third and final section, the concept that the structural organization of the pallium in actinopterygians can be fully explained by a simple eversion of its walls, and the various theories, according to which the eversion is complicated by extensive shifts of its constituent cell groups, are discussed and evaluated. It is concluded that there are no reasons to doubt that the pallium of actinopterygian fishes is the product of a simple and complete eversion.

Analysis of the structure of the brain stem of mammals by means of a modified D'Arcy Thompson procedure.

In his famous book, 'On Growth and Form', D'Arcy Thompson demonstrated that the shapes of related animals, or parts thereof, can be transformed into each other by a simple graphical procedure, called the method of coordinates. In this procedure, an object is inscribed in a net of Cartesian coordinates. It appeared that the shape of related objects could be characterized by means of simple, harmonious deformations of the initial orthogonal system of coordinates. Here, I demonstrate that: (1) the central nervous system contains a built-in, natural coordinate system; (2) differences in shape and proportion of cross sections through the brain stem of various mammals can be easily analyzed with the aid of this coordinate system, and (3) sets of structures in the mammalian brain stem, which are closely related to the neocortex, but form part of entirely different functional systems, form spatially constrained complexes, and have the capacity to expand jointly and harmoniously within these complexes.

The structural organization of the forebrain: a commentary on the papers presented at the 20th Annual Karger Workshop 'Forebrain evolution in fishes'.

During the 2008 Karger Workshop considerable progress was made towards defining a model or structural plan, valid for the prosencephalon of all vertebrates. The presentations demonstrated that the following features, which are valid for tetrapods, also hold true for most groups of fish: (1) The diencephalon proper is clearly composed of three neuromeres, p1-p3; (2) in the pallium four, rather than three, fundamental longitudinal zones can be distinguished; (3) during ontogenesis, numerous GABA-ergic elements migrate tangentially from the subpallium to the pallium.

On old and new comparative neurological sinners: the evolutionary importance of the membranous parts of the actinopterygian forebrain and their sites of attachment.

The forebrain of actinopterygian fishes differs from that of other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. This peculiar configuration of the actinopterygian forebrain results from an outward bending or eversion of its lateral walls during ontogenesis. Due to this eversion, the telencephalic roof plate is transformed into a wide, membranous structure that surrounds the dorsal and lateral parts of the solid lobes and is attached to their lateral or ventrolateral aspects. Another effect of the eversion is that the ventricular surface of the telencephalic lobes is very extensive, whereas their meningeal surface is small. In many recent publications on the forebrain of actinopterygian fishes, these structures are presented as solid lobes, without any reference to the fact that they are the product of an eversion process, and without any indication concerning the location and extent of their ventricular and meningeal surfaces. It is explained here that, in light of current concepts concerning the histogenesis of the brain, these omissions are intolerable. It is also strongly recommended that the location and extent of these surfaces should always be clearly indicated in brain sections in general, because the simple notion that in the brain of vertebrates the ventricular surface is on the inside and the meningeal surface on the outside has numerous and notable exceptions.

The forebrain of actinopterygians revisited.

The forebrain of actinopterygian fishes differs from that of other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. Comparative anatomical and embryological studies have shown that the unusual configuration of the forebrain in actinopterygians results from an outward bending or eversion of the dorsal portions of its lateral walls. Due to this eversion, the telencephalic roof plate is transformed into a wide, membranous structure which surrounds the dorsal and lateral parts of the solid lobes and is attached to their lateral or ventrolateral aspects. The taeniae, i.e. the lines of attachment of the widened roof plate, represent important landmarks in actinopterygian forebrains. In the present paper, the process of eversion is specified and quantified. It is pointed out that recent suggestions to modify the original eversion concept lack an empirical basis. Eversion is the antithesis of the inward bending or inversion that occurs in the forebrains of most other vertebrates. The forebrain lobes in actinopterygians, like those in other vertebrates, comprise a pallium and a subpallium, both of which include a number of distinct cell masses. The morphological interpretations of these cell masses over the past 130 years are reviewed and evaluated in light of a set of carefully selected criteria for homologous relationships. Special attention is paid to the interpretation of a cell mass known as Dp, situated in the caudolateral portion of the pallium in teleosts (by far the largest clade of living actinopterygians). Based on its position close to the taenia, and given the everted condition of the pallium in teleosts, this cell mass clearly corresponds with the medial pallium in inverted forebrains; however, Dp receives a dense olfactory input, and it shares this salient feature with the lateral pallium, rather than with the medial pallium of inverted forebrains. There is presently no consensus regarding the homology of Dp. Several recent authors [Wullimann and Mueller, 2004; Yamamoto et al., 2007] consider the lateral pallium in inverted forebrains and Dp in teleosts to be homologous because they believe that these cell masses originate from the same germinative zones, but that Dp attains its ultimate position only through migration. On the other hand, the present author believes that Dp is situated in the immediate vicinity of its germinative zone and that it represents a specialized part of the lateral pallial zone in teleosts, a zone that can be homologized topologically with the medial pallium in inverted forebrains. Further, it is proposed that the lateral olfactory tract in teleosts, which supplies most of the olfactory fibers to Dp, is not homologous to the same-named tract in the inverted forebrains of most other vertebrates.

Deuterostome brains: synopsis and commentary.

The living deuterostomes comprise six monophyletic groups: (1) echinoderms + hemichordates, (2) tunicates, (3) cephalochordates, (4) myxinoids, (5) petromyzontoids, and (6) gnathostomes. The morphotype of the craniote (myxinoids + petromyzontoids + gnathostomes) central nervous system (CNS) comprises a fixed number of histogenetic units, formed by the intersection of transversely oriented neuromeres and longitudinally arranged zones. A well-developed built-in, natural coordinate system adds the third dimension to this morphotype. The classical subdivisions of the craniote CNS: prosencephalon (P), mesencephalon (M), rhombencephalon (R), and spinal cord (S) are each composed of a number of neuromeres. Chordates (larval tunicates + cephalochordates + craniotes) share a highly characteristic axial complex, encompassing a dorsal tubular CNS, a notochord and bilateral series of segmental muscles. In all chordates the CNS can be divided into a rostral (P-like + M-like), an intermediate (R-like) and a caudal (S-like) sector, and sets of homologous developmental genes play a role in this tripartitioning. There are no indications for the presence of olfactory or other telencephalic regions in the brain of non-craniote chordates. Convincing evidence that parts of the chordate CNS are homologous to parts of the larval or adult CNS of non-chordate deuterostomes (echinoderms + hemichordates) is lacking. The dorsal tubular CNS is most probably a chordate autapomorphy.

Ultrastructural Characterization of Adrenocorticotrope Hormone (ACTH) Immunoreactive Fibres in the Mesencephalic Central Grey Substance of the Rat.

The fine structural localization of fibres immunoreactive for the adrenocorticotrope hormone (ACTH) was studied in the mesencephalic central grey substance (MCG) of the male Wistar rat. Light microscopically, varicose ACTH-immunoreactive fibres were found throughout the MCG in a dorsal, lateral and ventral, periventricular position. Electron microscopically, the immunoreactivity was most prominent in the direct vicinity of electron-dense secretory granules in axonal varicosities, and, although to a lower degree, around other cytoplasmic organelles such as electron-lucent synaptic vesicles, mitochondria and microtubules. With serial section analysis two types of ACTH-immunoreactive varicosity were discerned. The first type is large, contains many, small electron-lucent synaptic vesicles, that are located in the vicinity of a morphologically well-defined synaptic contact. In this type of varicosity, large dense-core secretory granules are scarce. Immunoreactivity is low or absent, particularly near the active zone. The second type is strongly immunoreactive. It always contains many large, dense-core secretory granules; electron-lucent vesicles are rare. The smaller varicosities of this type never make synaptic contacts, but a few of the larger varicosities have synaptic contacts with dendrites of MCG cells.