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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.

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.

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.

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 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.

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.

Let us begin our discussion of the neural tube and its regional differentiation by looking at some historic pictures, one from His (1893b), and three from Karl Von Kupffer (1906).

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 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.

Total neuron numbers in the amygdala and in eight of its subnuclei were determined in 9 cases of Alzheimer's disease (AD) and in 6 age-matched controls (AMC). Total neuron numbers were obtained using the fractionator. A neuron loss of 56.3% for the left amygdala and 50.5% for the right amygdala in AD was found, being more severe than previously reported. The subdivisions showed a differential neuron loss ranging from 35.5% in nucleus lateralis of the right amygdala to 70.4% in the nucleus basalis accessorius of the right amygdala. Moreover, a shift in size distribution to smaller neurons could be demonstrated. No left-right hemispheric differences were detected in total neuron numbers in AD and AMC.

According to Wilhelm 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 centres (superior and inferior olives). Nevertheless the ‘functional zonal model’ has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioural 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 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.

Orientation. Development. Gross anatomy. Blood supply, meninges and liquor system. Brain slices and microscopical sections. Topography of spinal cord, brain stem and cerebellum. Diencephalon: introduction and epithalamus. Diencephalon: dorsal thalamus. Diencephalon: ventral thalamus. Diencephalon: hypothalamus. Telencephalon: introduction and olfactory system. Telencephalon: hippocampus and related structures. Telencephalon: amygdala and claustrum. Telencephalon: basal ganglia. Telencephalon: neocortex. Functional systems.- General sensory systems and taste. Vestibular system. Auditory system. Visual system. Cerebellum. Motor systems. Limbic system

The boundaries of the medial forebrain bundle (MFB) of the rat have been presented in previous work on the structure of this fiber system (Nieuwenhuys et al.: J. Comp. Neurol. 206:49-81, '82). Neuronal cell bodies within these outlines constitute the bed nucleus of the MFB. Many fiber components of the MFB appeared to be spatially arranged within the bundle and featured an orderly topography (Veening et al.: J. Comp. Neurol. 206:82-108, '82). As the fibers of the MFB are thought to be a major source of afferents to the bed nucleus (Millhouse: In P. J. Morgane and J. Panksepp (eds): Anatomy of the Hypothalamus, Vol. 1. New York: Marcel Dekker, pp. 221–265, '79), the latter has been subjected in this and the companion study (Geeraedts et al.:J. Comp. Neurol. 294:537-568, '90) to a detailed cytoarchitectonic analysis. This analysis is based on continuous series sectioned in the three conventional planes. On the basis of cytoarchitectonic characteristics, including size and shape, staining intensity, packing density, and spatial orientation of the cell bodies, it was found that the bed nucleus of the MFB as described in the literature is by no means a cytoarchitectonic unit per se. Rather, the neuronal cell population located within the telencephalic stream of the MFB can be parcellated into a number of cellular groups, which partly or entirely belong to more-or-less known basal telencephalic structres. These structures are designated here as the MFB-related areas. They correspond largely to the subcommissural substantia innominata (SIC), the sublenticular substantia innominata (SIL), the nucleus of the diagonal band of Broca, the olfactory tubercle, the magnocellular preoptic nucleus (POMA), the lateral preoptic area (LPOA), and the interstitial nucleus of the stria medullaris (ISM). The complex of the MFB-related areas is surrounded by the following cellular entities: the nucleus accumbens (ACB), the caudatus-putamen region (CPU), the globus pallidus (GP), the bed nucleus of the stria terminalis (BST), the anterior amygdaloid area (AAA), the amygdaloid nuclear complex (A), the medial preoptic area (MPOA)and the anterior hypothalamic area (AHA). Both MFB-related areas and their surroundings have been identified and delimited in this study. This resulted in a new cytoarchitectonic atlas of the rat's basal telencephalon. Our atlas does not only show the relative positions of the above mentioned cellular groups, but also those of their subdivisions. The SIC, the SIL, the POMA and the LPOA have been parcellated into four, three, three, and six subareas, respectively; the GP, the BST, the MPOA, and the AHA into four, seven, fourteen, and six subareas, respectively. Several of these subdivisions have not been identified previously. The amygdaloid nuclear complex was not further parcellated cytoarchitectonically, as this was felt to be beyond the scope of our study. In preparing the atlas, it was kept in mind that the basal telencephalon should be parcellated in cellular groups and subgroups easily recognizable even by investigators not well trained in cytoarchitectonics. When the outlines of the MFB on the levels 1 to 4 of the atlas of the bun- dle (Nieuwenhuys et al.: J. Comp. Neurol. 206:49-81, '82) are superimposed upon the corresponding tracings of our cytoarchitectonic atlas, the following cellular groups appear to constitute the rostral or telencephalic part of the bed nucleus of the MFR: the deep layer of the olfactory tubercle, the magnocellu- lar preoptic nucleus, the horizontal limb of the diagonal band of Broca, the lateral preoptic area and the sublenticular substantia innominata. After superimposing the areas of labeling of 21 autoradiographically identified fiber components of the MFB (Veening et al.: J. Comp. Neurol. 206:82-108, '82) upon our tracings of the rostral bed nucleus, a remarkable correspondence appeared with the borders of the cytoarchitectonically defined cellular entities and those of the traversing fiber components to and from specific origins and destinations. These findings can be summarized as follows: the ventrolateral or POMA-section of the MFB is occupied by olfactory related fibers; the ven- tromedial or LPOA-section of the MFB contains septal, preoptic, and medial hypothalamic fibers; and the dorsal or SIL-section of the MFB contains mesolimbic fibers, including fibers arising from the central amygdaloid nucleus, the bed nucleus of the stria terminalis, the ventral tegmental area, and the parabrachial nuclei of the brainstem region. Further morphological analysis of the connectivity of the neurons of the cellular entities of the rostral bed nucleus and their proposed dendritic rela- tionships with collaterals of the fibers of the MFB-components will provide more profound information on the intrinsic organization of the MFB and its so-called bed nucleus.

In the preceding study (Geeraedts et al.: J. Comp. Neurol. 294:507-536, '90), the rostral or telencephalic portion of the rat's bed nucleus of the medial forebrain bundle (MFB) has been parcellated into several cytoarchitectonically distinct cellular groups and subgroups. The purpose of the present investigation is to subject the caudal or lateral hypothalamic (LH) portion of the MFB bed nucleus to a detailed cytoarchitectonic analysis. This analysis is based on the same materials, methods, and cytoarchitectonic criteria that were also employed in the preceding study. In contrast to descriptions in the literature, it was found that the LH-region constitutes a very heterogeneous population of neurons with an evident arrangement into groups, several of which have not been identified previously. Many of these cellular groups are partly or entirely located within the boundary of the LH-trajectory of the MFB as previously established by Nieuwenhuys et al. (J. Comp. Neurol. 206:49-81, '82). These groups are designated here as the MFB-related cellular groups. They appear to be arranged into two longitudinal zones. Both zones are caudally replaced by the ventral tegmental area (VTA) and a part of the mesencephalic tegmentum (TEGM1). The lateral zone lies in close proximity to the internal capsule/cerebral peduncle and comprises the following cellular groups: the ventrolateral subarea of the lateral hypothalamic area (LHVL), the anterolateral subarea of the lateral hypothalamic area (LHAL), the lateral tuberal nucleus (TUL), the pre-subthalamic nucleus (PSUT), the retro-subthalamic nucleus (RSUT), the anterodorsal subarea of the lateral hypothalamic area (LHAD), and the lateral hypothalamic nucleus (LHN). The medial zone consists of the following cellular groups: the intermediate hypothalamic area (IHA), the medial tuberal nucleus (TUM), the perifornical nucleus (PFX), the lateral supramammillary nucleus (SUL), the submammillothalamic nucleus (SMT), and the nucleus geminus posterior (GEP). The cellular groups of the medial zone together with the tuberomammillary nucleus (TUMM) are positioned at the interface between the lateral and the medial hypothalamus, and form an array of cellular groups indicated in our study as the intermediate division of the hypothalamus. The MFB-related cellular groups are dorsally, medially, ventrally, and laterally surrounded by rather well-known brain structures. Both the MFB-related cellular groups and the surrounding structures have been identified and delimited. This resulted in a new, elaborate cytoarchitectonic atlas of the rat's lateral hypothalamic region. When the outlines of the MFB on the levels 5-9 of the atlas of the bundle (Nieuwenhuys et al.: J. Comp. Neurol. 206:49-81, '82) are superimposed upon the corresponding tracings of our cytoarchitectonic atlas, the following cellular groups appear to constitute the caudal or lateral hypothalamic portion of the bed nucleus of the MFR: the LHVL, the LHAL, the LHAD, the TUL, the PSUT, the RSUT, the LHN. The GEP, the TEGM1, and, moreover, the lateral portions of the IHA, the TUM, the PFX, the SUL, and the SMT. After super- imposing the areas of labeling of 21 autoradiographically identified fiber com- ponents of the MFB (Veening et al.: J. Camp. Neurol. 206:82-108, '82) upon the corresponding tracings of our atlas, we noted a certain correspondence with the borders of the cytoarchitectonically defined cellular groups and those of the fiber components. These data can be summarized as follows: the inter- mediate division of the hypothalamus contains septal, medial preoptic, and medial hypothalamic fibers; the ventrolateral or TUL/LHVL-part of the MFB is occupied by olfactory related fibers; the dorsolateral part of the MFB, occupying the dorsolateral portion of the LHN-region, is traversed by meso- limbic fibers; the central and dorsomedial portions of the LHN-region are occupied by fibers arising from the lateral hypothalamus, the bed nucleus of the stria terminalis, the ventral tegmental area, and presumably also by fibers from (until now) unknown origin or destination.

Marked neuron loss in the nucleus basalis of Meynert complex (NBMC) in Alzheimer's disease has repeatedly been reported in the literature. However, most of these studies quantitated only magnocellular, hyperchromatic (putative cholinergic) neurons of just a small part of the NBMC, and counts were expressed as numerical density. Applying a 3-dimensional-sampling design throughout the entire rostrocaudal extent of the NBMC and sampling neurons regardless of their size and staining characteristics, an overall neuron loss of only 15.5% was demonstrated for the whole NBMC. Neuron loss varied from 0% rostrally in the NBMC up to 36% in the most caudal part of the nucleus basalis of Meynert. Moreover, a significant increase in the number of small-sized neurons and a significant decrease in the number of large, putative cholinergic neurons could be detected, suggesting that apart from neuron loss neuron shrinkage appears to be another characteristic neuropathological feature of this degenerating cholinergic NBMC system. Preservation of these magnocellular cholinergic neurons in shrunken form renders it likely that cholinergic dysfunction, characteristic of Alzheimer's disease, may be responsive to neurotrophic influences.

Publisher Summary In this chapter, the morphological evidence for the occurrence of volume transmission in vertebrates and invertebrates are discussed. The assembled data is also surveyed and placed in a comparative and a functional perspective. While studying the morphological evidence in invertebrates, the relevant data on the occurrence of other forms of intemeuronal communication are included and special attention will be paid to the structural relations in the first three phyla of the animal kingdom— that is, the Placozoa, the Porifera, and the Cnidaria. From a survey of the ultra structural data discussed, it is concluded that volume transmission is most probably very common in the greater limbic system of mammals, and that this mode of inter neuronal communications also occurs in the neostriatum, the hippocampus, and the neocortex of this group. From the studies in invertebrates, it is concluded that volume transmission is dominant in the neuropils of many invertebrates.

Comparative neuroanatomy or neuromorphology is a biological subdiscipline, the central aim of which is: the elucidation and interpretation of the form, structure and ultrastructure of the nervous system (cf. Sect. 6.3.1).

The preceding chapter dealt with the structure and function of the cellular elements in the central nervous system. In the present chapter the same features of assemblies of neurons will be discussed. The approach will be purely morphological, passing from simple to complex and from generalized to specialized, although some theories about the phylogenetic changes in the vertebrate neuraxis will be considered. Following some notes on grey and white matter, the periventricular grey and the neuropil and fibre zone which covers this grey peripherally in the brain of many different anamniotes will be covered. The neuropil and its differentiation into various zones or sheets will next be considered, and then the organisation of the diffuse or reticular grey will be discussed. Having dealt with the structure and function of simple and generalised grisea, we will then survey the organisation of more complex neuronal assemblies. Attention will be paid to the position, cytoarchitecture and organisation of cell masses or nuclei as well as to their dendritic and axonal ramifications and extrinsic connections. Many grisea in the central nervous system of vertebrates show a laminar organisation, and this interesting feature will be treated in some detail. The last section is devoted to the chemoarchitecture of grisea.

By way of introduction, an outline is presented of the origin and evolutionary development of the neocortex. A cortical formation is lacking in amphibians, but a simple three-layered cortex is present throughout the pallium of reptiles. In mammals, two three-layered cortical structures, i.e. the prepiriform cortex and the hippocampus, are separated from each other by a six-layered neocortex. Still small in marsupials and insectivores, this "new" structure attains amazing dimensions in anthropoids and cetaceans. Neocortical neurons can be allocated to one of two basic categories: pyramidal and nonpyramidal cells. The pyramidal neurons form the principal elements in neocortical circuitry, accounting for at least 70% of the total neocortical population. The evolutionary development of the pyramidal neurons can be traced from simple, "extraverted" neurons in the amphibian pallium, via pyramid-like neurons in the reptilian cortex to the fully developed neocortical elements designated by Cajal as "psychic cells". Typical mammalian pyramidal neurons have the following eight features in common: (1) spiny dendrites, (2) a stout radially oriented apical dendrite, forming (3) a terminal bouquet in the most superficial cortical layer, (4) a set of basal dendrites, (5) an axon descending to the subcortical white matter, (6) a number of intracortical axon collaterals, (7) terminals establishing synaptic contacts of the round vesicle/asymmetric variety, and (8) the use of the excitatory aminoacids glutamate and/or aspartate as their neurotransmitter. The pyramidal neurons constitute the sole output and the largest input system of the neocortex. They form the principal targets of the axon collaterals of other pyramidal neurons, as well as of the endings of the main axons of cortico-cortical neurons. Indeed, the pyramidal neurons constitute together a continuous network extending over the entire neocortex, justifying the generalization: the neocortex communicates first and foremost within itself. The typical pyramidal neurons represent the end stage of a progressive evolutionary process. During further development many of these elements have become transformed by reduction into various kinds of atypical or aberrant pyramidal neurons. Interestingly, none of the six morphological characteristics, mentioned above under 1-6, has appeared to be unassailable; pyramidal neurons lacking spines, apical dendrites, long axons and intracortical axon collaterals etc. have all been described. From an evolutionary point of view the typical pyramidal neurons represent not only the principal neocortical elements, but also the source of various excitatory local circuit neurons. The spiny stellate cells, which are abundant in highly specialized primary sensory areas, form a remarkable case in point.(ABSTRACT TRUNCATED AT 400 WORDS)

The efferent connections of the hypothalamic area of the rat, where attack behaviour can be elicited by electrical stimulation, were studied using iontophoretic injections of Phaseolus vulgaris-leucoagglutinin. Specificity for the hypothalamic "attack area" was investigated by comparison with efferents of hypothalamic sites outside the attack area. The hypothalamic attack area consists of the intermediate hypothalamic area and the ventrolateral pole of the ventromedial hypothalamic nucleus. Fibres from the hypothalamic attack area, as well as fibres from several other hypothalamic sites, form diffuse fibre "streams" running rostrally or caudally. Many varicosities that are found on the fibres suggest, that these fibres are capable of influencing many brain sites along their way. Projection sites were found throughout the brain. In the comparison between attack area efferents and controls, many overlapping brain sites were found. Hypothalamic efferents preferentially originating in the largest part of the attack area, i.e. the intermediate hypothalamic area, were found in the mediodorsal and parataenial thalamic nuclei. Within the septum, a spatial organization of hypothalamic innervation was found. Fibres from the attack area formed specialized "pericellular baskets" in the dorsolateral aspect of the intermediate part of the lateral septal nucleus. Fibres from other hypothalamic sites were found in other septal areas and did not form these septal baskets. Within the mesencephalic central gray, fibres from the attack area were found specifically in the dorsal part and dorsal aspect of the lateral part of the central gray. Physiological and pharmacological studies have shown that several brain sites are involved in different aspects of aggressive behaviour. Some of these areas, as for instance the dorsomedial thalamic nucleus, septum and central gray, are innervated by efferents from the hypothalamic attack area, whereas other sites, like ventral premammillary nucleus and ventral tegmental area, are not. It is concluded from the present findings, that a number of brain sites, that are known to be involved in agonistic behaviour, receive hypothalamic information preferentially from the hypothalamic attack area through diffusely arranged varicose fibres. The function of each connection in the regulation of specific behaviours remains to be further investigated.

This paper presents a survey of the cell masses in the brainstem of the generalized actinopterygian fish Amia calva, based on transversely cut Nissl-, Kluver-Barrera-, and Bodian-stained serial sections. This study is intended to serve a double purpose. First it forms part of a now almost complete series of publications on the structure of the brainstem in representative species of all groups of 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 this 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 (Nieuwenhuys [1974] J. Comp. Neurol. 156:255-267). The second purpose of the present paper is to provide a cytoarchitectonic basis for experimental analysis of the fiber connectivity in the brainstem of Amia. Five longitudinal sulci–the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, the sulcus intermedius dorsalis, and the sulcus lateralis mesencephali–could be distinguished. Some shorter grooves, present in the isthmal region, clearly deviate from the overall longitudinal pattern of the other sulci. Although in Amia most neuronal perikarya are contained within a diffuse periventricular gray, 40 cell masses could be delineated: Eight of these are primary efferent or motor nuclei, 10 are primary afferent or sensory centers, seven are considered to be components of the reticular formation, and the remaining 15 may be interpreted as “relay” nuclei. The topological analysis yielded the following results. In the rhombencephalon the gray matter is arranged in four longitudinal columns or areas, termed area ventralis, area intermedioventralis, are intermediodorsalis, and area dorsalis. The sulcus intermedius ventralis, the sulcus limitans, and the sulcus intermedius dorsalis mark the bounderies between these morphological entities. These longitudinal areas 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 nuclei. The four longitudinal zones cannot be distinguished in the mesencephalon nor can the sulcus limitans be recognized here. Functionally, however, the medial part of the tegmentum mesencephali may be considered the rostral extremity of the somatomotor column, whereas the remainder of the midbrain contains a number of somatosensory centers. © 1994 Wiley-Liss, Inc.

The efferent connections of the hypothalamic area, where grooming can be elicited by local electrical stimulation or injection of various substances, were studied using iontophoretic injections of Phaseolus vulgaris leucoagglutinin. This hypothalamic "grooming area" consists of parts of the hypothalamic paraventricular nucleus and of the dorsal hypothalamic area. The specificity of these efferents for the hypothalamic "grooming area" was investigated by comparison with efferents of hypothalamic sites adjacent to this area. In addition, the distribution of oxytocinergic fibres was studied, since oxytocinergic neurons are present in the hypothalamic "grooming area" and oxytocin is possibly involved in grooming behaviour. The efferents of the hypothalamic "grooming area" as well as of hypothalamic sites surrounding this area and the oxytocinergic fibres studied do not form well determined bundles, but rather spread out throughout the hypothalamus. Clusters of fibres could be traced rostrally and caudally, forming diffuse fibre "streams". Three rostral, two thalamic and three caudal fibre "streams" have been distinguished along which efferent fibres innervate different brain areas. The many varicosities on labelled fibres "en passant" suggest that hypothalamic fibres are able to influence many parts of the brain along their way. The anterior periventricular area, the median preoptic nucleus, the ventral tegmental area and nucleus of the solitary tract were found to be more or less specifically innervated by hypothalamic "grooming area" fibres and oxytocinergic fibres. Other brain areas, like the septum, the medial amygdaloid nucleus, the central gray and the paraventricular nucleus of the thalamus were found to receive efferent projections from the hypothalamic "grooming area" and hypothalamic loci outside this area, as well as from the oxytocinergic system. Within the septum and the mesencephalic central gray, differences in the spatial organization of terminating fibres from the hypothalamic "grooming area" and hypothalamic "non-grooming" sites have been found. Fibres from the grooming area clustered in the ventral part of the lateral septal nucleus, while fibres from surrounding hypothalamic loci innervated other parts of that brain area. In the central gray, fibres from the hypothalamic "grooming area" clustered in rostrodorsal and caudoventral parts. A number of brain areas, that are innervated by hypothalamic "grooming area" fibres and oxytocinergic fibres, like central gray, ventral tegmental area and the noradrenergic A5 area, have been reported previously to be involved in grooming behaviour. It is concluded from the present findings, that the hypothalamic "grooming area" has preferential connections with a number of brain sites, not shared with hypothalamic projections from outside the "grooming area".(ABSTRACT TRUNCATED AT 400 WORDS)

Projections descending from the hypothalamus to the PAG are in the rat characterized by the fact that they have in common with other ascending and descending projections the principle of termination within restricted parts of the PAG (see Blomqvist and Craig; Shipley et al., this volume). For that reason, we have to pay first some attention to the cytoarchitecture and the possible subdivisions of the PAG. On that basis, the descending projections will be described and compared with data obtained from the literature.

This paper is the first of a projected series of studies on the structure and composition of the medial forebrain bundle (MFB) of the rat and the relations of this fiber system to its bed nucleus, the lateral hypothalamic area. The first part of the paper comprises an extensive review of literature on the MFB from its discovery by Ganser in 1882 to the present. This review serves as the basis for an evaluation of our present-day knowledge of the organization of the MFB, which is presented in the second part of this paper. Despite the wealth of information available on the origins and sites of termination of the axons that constitute the MFB, surprisingly little attention has been given to the bundle itself, to its topographic boundaries, its fiber composition, or to the spatial arrangement of its constituent components. These features of the MFB as it extends through the lateral preoptic and lateral hypothalamic areas have been analyzed in normal Klüver-Barrera- and Bodian-stained material. From this analysis, a detailed atlas of the MFB and some of the surrounding structures has been prepared. This atlas, which forms the third section of this paper, illustrates the appearance and organization of the MFB at ten equidistant levels through the lateral preoptic and lateral hypothalamic continuum.

SYNOPSIS. The brain of actinopterygian fishes can be subdivided into five principal parts, rhombencephalon, cerebellum, mesencephalon, diencephalon and telencephalon, each of which contains a number of separate morphological entities: nuclei, areas or zones. Analysis of the origin and termination of the cranial nerves and their components reveals that many of the morphological entities distinguished in the actinopterygian brain can be interpreted in terms of elementary sensory and motor functions. Experimental anatomical and physiological studies on the fiber connections of the entities thus defined have led to a functional interpretation of many other parts of the brain. Thus, the central circuitry related to such sensory functions as hydrodynamic pressoreception, electroreception, vision, gustation and olfaction are well-known, and the same holds true for the motor systems related to feeding and locomotion. However, there are still many regions in the actinopterygian brain the functional significance of which is poorly understood, and it should be emphasized that most of our knowledge on the organization of the brain of this group rests merely on observations in teleosts. One of the most interesting aspects of actinopterygian neurobiology is that the telencephalon in this group develops in a way which differs fundamentally from that found in all other craniates, and that the telencephalon shows a marked progressive differentiation in the series: polypterids—chondrosteans—halecomorphs—teleosts.

The ventricular sulcal pattern and the cytoarchitecture of the brainstem of Xenopus laevis, a pipid frog which retains a lateral line system throughout life, were studied in transverse Nissl- and Kluver-Barrera-stained serial sections. Four distinct longitudinal sulci, the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, and the sulcus medianus superior, could be distinguished. With the aid of the usual cytoarchitectonic criteria 42 cell groups were delineated; seven of these are primary efferent or motor nuclei, 13 are primary efferent or sensory centers, seven nuclei are considered to be components of the reticular formation, and the remaining 15 cell masses can be indicated as “relay” nuclei. In order to provide a basis for experimental work, the topographical position of the nuclei is illustrated in photomicrographs of representative levels and in graphical reconstructions. The distribution of the cell masses and their relations to the ventricular sulci were studied with the aid of the reconstruction procedure termed topological analysis (cf. Nieuwenhuys, '74; Fig. 19). This analysis yielded the following results. The sulcus limitans extends throughout almost the entire brainstem, dividing this part of the brain into a motor basal plate and a sensory alar plate. The cell masses in the rhombencephalic basal plate fit into two longitudinal zones, a medial area ventralis and a lateral area intermedioventralis. The former contains somatomotor centers of primary and higher order, whereas the latter is composed of three primary visceromotor nuclei and one visceromotor coordinating center. The rhombencephalic alar plate is occupied by viscerosensory, general somatosensory, and special somatosensory cell masses. Two centers, the nucleus fasciculi solitarii and the nucleus visceralis secundarius, represent together a discontinuous viscerosensory zone, which is situated immediately dorsal to the sulcus limitans. The general somatosensory nuclei, i.e., the gracile and cuneate nuclei, the nucleus tractus descendens of V, and the nucleus princeps of V constitute a zone which largely overlaps the viscerosensory zone. The special somatosensory area, i.e., the area of termination of (1) primary vestibular, (2) primary acoustic, and (3) lateral line nerve fibers, is strongly developed and occupies a considerable part of the alar plate. Presumably, the fibers of each of the three categories mentioned terminate in three separate zones of gray. The midbrain can also be subdivided bilaterally into a basal plate and an alar plate. The former occupies the medial part of the tegmentum mesencephali and may be considered as the rostral extreme of the somatomotor zone. The latter comprises the lateral tegmentum and the tectum, areas which are chiefly occupied by special somatosensory (visual, acoustic, lateral line) centers.

Some projections from the lateral hypothalamic area in the rat have been investigated, using combinations of fluorescent tracers, injected into several different parts of the central nervous system. Projections appear to arise from loosely organized assemblies of neurons, called sets and from more densely packed assemblies, called clusters. The sets and clusters vary considerably in position and in distinctness of their borderlines. Even within extensive and vaguely denned sets, however, high concentrations of labeled neurons may be present at specified sites in the lateral hypothalamus. Such concentrations are observed in the transitional area of the zona incerta and the dorsal part of the lateral hypothalamus and in the ventrolateral part of the hypothalamus, bordering the cerebral peduncle and the subthalamic nucleus, in both cases after injections into some “autonomic centers” in the brainstem, such as the parabrachial nuclei and the dorsal vagal complex. Sets and clusters may overlap considerably. Within the fields of overlap the number of double labeled neurons may vary from almost zero up to more than 50%, depending on the injection sites. The results show that different parts of the lateral hypothalamus in the rat have different efferent relationships. Combination of the results of the present study with known data concerning the afferent relationships, the cytoarchitecture and behavioral functions of the lateral hypothalamic area, suggests that different parts of this entity are involved in different regulatory and behavioral functions.

The ventricular sulcal pattern and the cytoarchitectonic organization of the brain stem of the turtle Testudo hermanni have been studied in transversely cut, Nissl stained serial sections. Four longitudinal sulci, the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans and the sulcus medianus superior could be distinguished. With the aid of the usual cytoarchitectonic criteria 54 cell groups have been delimited; 12 of these are primary efferent or motor nuclei, 13 are primary afferent or sensory centers; 10 of the nuclei distinguished are considered as belonging to the reticular formation. The remaining 19 cell masses can be indicated as “relay” nuclei. In order to provide a basis for experimental hodological work the topographical position of the nuclei is illustrated in photomicrographs of representative levels and in graphical reconstructions. In order to elucidate the morphological pattern of the cell masses and their relationship to the ventricular sulci the brain stem was subjected to a topological analysis. Essentially this method requires that (1) the cell masses are projected upon the ventricular surface and that (2) this surface, with its sulci marked on it and with the outlines of the subjacent cell masses projected upon it, is flattened out. This analysis yielded the following results: The sulcus limitans extends throughout the rhombencephalon, dividing this brain part into a basal plate and an alar plate. In the basal plate the sulcus intermedius ventralis marks the boundary between an area ventralis and an area intermedioventralis containing, respectively, the somatic motor nuclei of primary and higher order, and the visceral motor centers. Yet the terms somatic motor zone and visceral motor zone are not applicable to these two areas as a whole since both contain a number of non-motor centers. Thus the intermedioventral zone harbours two general somatic sensory centers, i.e., the spinal- and princeps nuclei of V. The medial parts of the tegmentum isthmi and of the tegmentum mesencephali contain somatic motor centers of primary and higher order, and thus may be considered rostral continuations of the rhombencephalic ventral zone. The rhombencephalic alar plate contains visceral sensory, general somatic sensory and special somatic sensory centers, but these do not show a simple ventrodorsal arrangement. A prominent feature is that the special somatic sensory nuclei of termination of VIII, the cerebellar nuclei, and a number of special somatic sensory centers of higher order together constitute a continuous zone which extends from the rhombencephalic alar plate, via the isthmus into the lateral part of the tegmentum mesencephali. In the isthmus region the sulcus limitans does not mark the ventral boundary of this zone, but rather passes over its middle.

The medial forebrain bundle (MFB) is a complex fiber system that courses through and partly arises and partly terminates within the lateral preoptic and lateral hypothalamic areas. It consists mainly of thin fibers and may be comprised of as many as 50 descending and ascending components of varying lengths and of different origins and/or destinations (Nieuwenhuys et al., '82). With the aid of an an atlas of the MFB and the surrounding brain areas in the rat presented in the preceding paper (Nieuwenhuys et al., '82), the position and topographic relationships of some 21 components of the bundle have been analyzed in detail, in brains that had been prepared for autoradiography following injections of tritiated amino acids into a number of structures that are known to contribute fibers to the MFB. From this analysis it is clear that most of the labeled components occupy specific and rather constant positions within the MFB. For example, the ascending components are largely confined to the dorsal half of the bundle; those arising from the medial preoptic area and the various hypothalamic nuclei are distributed rather diffusely over much of the MFB; and the descending components that arise from the olfactory tubercle and the magnocellular preoptic nucleus are confined to restricted parts of the bundle. These findings indicate that the neurons which occupy different parts of the lateral hypothalamic area probably receive distinctive inputs, and to a first approximation these are likely to be determined principally by their position within the MFB.

In this book an attempt has been made to summarize our present-day knowledge of the neuromediator-specified neuronal populations in the mammalian central nervous system, and to explore the relations between what are now called ‘classical neuroanatomy’ and ‘chemical neuroanatomy’. Many uncertainties have been expressed and few definitive conclusions have been drawn. One of the major difficulties encountered was that opportunities for an immunohistochemical approach to the central nervous system offered themselves to neurosciences at a time when the facade, not to mention the building, of classical neuroanatomy was by no means finished. Moreover, the set of new techniques triggered a tremendous explosion of research which has led — as explosions usually do — to the generation of numberless fragments (‘data’), but not in itself to any great gain in our understanding and insights. Times in which explosions occur do not invite reflexion, and it is no exaggeration to say that, at present, theory formation in neurobiology lags far behind. Yet, if any real progress is to be made, serious attempts are compellingly necessary to create a new framework within which classical neuroanatomy and chemical neuroanatomy will harmoniously converge towards a new neurobiology. Needless to say, the creation of such a new framework is far beyond the capability of a single individual. It should therefore be appreciated from the outset that the concluding comments which follow have only the intention of emphasizing a few aspects which might be relevant to such an enterprise.

In the preceding chapter I have attempted to characterize the present state of chemical neuroanatomy and its relations to classical neuroanatomy in twenty statements, and I have added shorter or longer comments to each of these. In this chapter I will develop a new view on the organization of certain parts of the neuraxis. In doing so I will not hesitate to go clearly beyond well-established data at some points. Thus, the character of this chapter is speculative and differs considerably from that of the preceding ones. Nevertheless, the format of statements followed by comments will be maintained, and the numbering of the statements will also be continued. An important advantage of this mode of recording is that it facilitates cross-reference of the various statements.

In the preceding chapter a survey of a number of chemically defined cell groups and pathways has been presented. In this chapter I shall attempt (a) to draw certain general conclusions from the data gathered, and (b) to explore the relations between ‘classical’ and ‘chemical’ neuroanatomy. Before embarking on the enterprise just outlined it seems proper to indicate the limitations of this study and to articulate a number of caveats.

Publisher Summary This chapter focuses on the comparative anatomy of the cerebellum. It presents a survey of the comparative anatomy of the cerebellum by way of introduction to this meeting which will be devoted almost entirely to the structure and function of the mammalian cerebellum. With regard to proportionate size and shape the cerebellum is doubtless the most variable part of the central nervous system, and its histological structure is also subject to considerable differences among the various groups of vertebrates. The corpus cerebelli receives its sensory input from various sources. Spino-cerebellar and trigemino-cerebellar tracts, conveying proprioceptive and exteroceptive information toward this part of the cerebellum, have been described for all groups of vertebrates. In mammals the ‘direct’ spino-cerebellar tracts are augmented by several ‘indirect’ systems, which have a relay nucleus in the medulla oblongata (n. cuneatus externus, n. funiculi lateralis, n. reticularis paramedianus). In addition to the spino-cerebellar and trigemino-cerebellar tracts, which may be termed the ascending afferents, the corpus cerebelli receives numerous fibres which descend from more rostrally situated centres.

Publisher Summary This chapter presents a survey of the comparative anatomy of the parts of the telencephalon that are entirely or predominantly related to the sense of smell. The structures included in this so-called “rhinencephalo” display a great variety in proportionate size and degree of differentiation, but nevertheless it is possible to recognize a common structural plan that underlies the morphology of this brain part in all groups of vertebrates. The central olfactory system of the various groups of submammalian vertebrates has been discussed. Attention is drawn first to the marked variations in development of the olfactory centres. It seems probable that the early vertebrates were endowed with a well developed olfactory apparatus, and that this macrosmatic condition has been maintained in the main line of vertebrate evolution. A fargoing regression of the olfactory apparatus and its centers has occurred at least 3 times in the course of phylogeny of the submammalian vertebrates, namely in the teleosts (Mormyridae), in the lizards (Chameleon, Anolis), and in birds. In all vertebrates, the primary olfactory elements are represented by neurosensory cells situated in the nasal epithelium. These elements are provided with extremely fine, unmyelinated axonal offshoots that convey the olfactory impulses to the bulbi.

The investigations of His, Herrick, Johnston and many others have led to the doctrine that the central nervous system fundamentally consists of a number of longitudinally arranged zones or columns, some of which are delimited from each other by distinct ventricular sulci. In order to facilitate the study of this basic morphological pattern in the brain stem, a procedure has been developed, making it possible to survey in one figure the neuronal structures and their relationship to the ventricular grooves in this region. Essentially this procedure 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, i.e., subjected to a one-to-one continuous topological transformation. Such a topological analysis was carried out on the brain stem of the lamprey, Lampetra fluviatilis, and yielded the following results: The sulcus limitans of His extends throughout the rhombencephalon, but does not enter the midbrain. The rhombencephalic basal plate can be clearly divided into a medial somato-motor, and a lateral viscero-motor zone. The somato-motor zone consists of a rostral extension of the spinal motor column and three reticular nuclei. Rostrally this zone is continuous with the tegmentum mesencephali, which contains another reticular nucleus and the superficial and deep nuclei of III. The reticular nuclei contain groups of large cells. On either side seven of these large cells, three in the midbrain, one in the isthmus and three in the hindbrain, are significantly larger than the others, and are designated as Muller cells. The viscero-motor zone is confined to the hindbrain. It consists of a continuous chain of discrete cell masses: the motor nuclei of V, VII, IX and X. This zone contains in addition the large Mauthner neuron, which is situated between the nuclei of V and VII. In the rhombencephalic alar plate, separate viscero-sensory and somatosensory zones could not be recognized. The delimitable nuclei in this region all belong to the somato-sensory octavo-lateralis complex. The latter complex extends rostrally into the very small cerebellum which, apart from a zone of periventricular gray and a nucleus cerebelli, harbours the motor nucleus of IV. The sensory centers of the midbrain, i.e., the torus emicircularis and the tectum are caudally continuous with the gray substance of the alar plate of the hindbrain. Large, presumably primary sensory, elements occur in the caudal and ventral part of the rhombencephalic alar plate. Such “dorsal cells” are also present in the spinal cord, but a midbrain equivalent, i.e., nucleus mesencephalicus of V, is entirely lacking.