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Stereotaxis is widely used in clinical neurosurgery, neuroradiosurgery, and neuroimaging. Yet, maps of brain structures obtained from post-mortem human brains are not usually presented in known stereotaxic coordinates. Post-mortem brain data given in stereotaxic coordinates would facilitate comparisons with in vivo human neuroimages and would also facilitate intra and inter-experiment comparisons. In this article, we present a crafted instrument for stereotaxic cutting of post-mortem human brain hemispheres. The instrument consists of a transparent methacrylate plate facing a mirror, four legs, and lateral regularly spaced columns permitting the insertion of large knives in-between the columns. This instrument can be built in any laboratory to obtain human brain slabs in the stereotaxic space of Talairach and Tournoux. We explain in detail the procedure for stereotaxic cutting of human brain hemispheres in the coronal plane, as well as the basis for calculating stereotaxic coordinates of histological sections obtained following the stereotaxic cutting protocol.

Neuromodulatory afferents to thalamic nuclei are key for information transmission and thus play critical roles in sensory, motor, and limbic processes. Over the course of the last decades, diverse attempts have been made to map and describe subcortical neuromodulatory afferents to the primate thalamus, including axons using acetylcholine, serotonin, dopamine, noradrenaline, adrenaline, and histamine. Our group has been actively involved in this endeavor. The published descriptions on neuromodulatory afferents to the primate thalamus have been made in different laboratories and are not fully comparable due to methodological divergences (for example, fixation procedures, planes of cutting, techniques used to detect the afferents, different criteria for identification of thalamic nuclei…). Such variation affects the results obtained. Therefore, systematic methodological and analytical approaches are much needed. The present article proposes reproducible methodological and terminological frameworks for primate thalamic mapping. We suggest the use of standard stereotaxic planes to produce and present maps of the primate thalamus, as well as the use of the Anglo-American school terminology (vs. the German school terminology) for identification of thalamic nuclei. Finally, a public repository of the data collected under agreed-on frameworks would be a useful tool for looking up and comparing data on the structure and connections of primate thalamic nuclei. Important and agreed-on efforts are required to create, manage, and fund a unified and homogeneous resource of data on the primate thalamus. Likewise, a firm commitment of the institutions to preserve experimental brain material is much needed because neuroscience work with non-human primates is becoming increasingly rare, making earlier material still more valuable, Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. CC and IP-S were the recipients of grants from Chair in Neuroscience UAM-Fundación Tatiana Pérez de Guzmán el Bueno, Spain. MAG-C was the recipient of a Beatriz Galindo senior research position in the School of Medicine, Universidad Autónoma de Madrid (BEAGAL18/00098) and of a Grant for I+D Projects to the Beatriz Galindo Program Researchers at Universidad Autónoma de Madrid (SI2/PBG/2020–00014) from the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Autónoma de Madrid in the line of action encouraging young research doctors, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation)

The primate thalamus has been subdivided into multiple nuclei and nuclear groups based on cytoarchitectonic, myeloarchitectonic, connectional, histochemical, and genoarchitectonic differences. Regarding parcellation and terminology, two main schools prevailed in the twentieth century: the German and the Anglo-American Schools, which proposed rather different schemes. The German parcellation and terminology has been mostly used for the human thalamus in neurosurgery atlases; the Anglo-American parcellation and terminology is the most used in experimental research on the primate thalamus. In this article, we review the historical development of terminological and parcellation schemes for the primate thalamus over the last 200 years. We trace the technological innovations and conceptual advances in thalamic research that underlie each parcellation, from the use of magnifying lenses to contemporary genoarchitectonic stains during ontogeny. We also discuss the advantages, disadvantages, and practical use of each parcellation.

Understanding the origin of Greek and Latin words used as metaphors to label brain structures gives a unique window into how scientific and medical knowledge was produced, preserved, and transmitted through generations. The history of the term thalamus exemplifies the complex historical process that led to the current anatomical terminology. From its first mention by Galen of Pergamon in the 2nd century A.D. to its definitive and current use by Thomas Willis in 1664, the thalamus had an epical journey through 1500 years across Europe, the Middle East, and the North of Africa. The thalamus was confusingly described by Galen, in the Greek language, as a chamber to the brain ventricles. The term thalamus was transferred from Greek to Syriac through the translations of Galen’s books done in Baghdad and also from Syriac to Arabic. Then, it was translated in Europe during the Middle Ages from the Arabic versions of Galen’s books to Latin. Later, during the Early Renaissance, it was translated again to Latin directly from the Greek versions of Galen’s books. Along this epical journey through languages, the term thalamus switched from referring to a hollow structure connected to brain ventricles to naming a solid structure at the rostral end of the brainstem. Finally, the thalamus was translated from Latin to modern languages, where it is used, until today, to name a nuclear complex of subcortical gray matter in the lateral walls of the third ventricle.

Parkinson’s disease (PD) is a neurodegenerative disease with both motor and non-motor manifestations. Hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. The relationship between hyposmia and PD remains elusive. Olfactory bulb (OB) pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. In this study we examined tissue levels of dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and their metabolites, of noradrenaline (NA) and of the amino acid neurotransmitters aspartate, glutamate, taurine and γ-aminobutyric acid in OBs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated Macaca fascicularis in different stages, includin g monkeys who were always asymptomatic, monkeys who recovered from mild parkinsonian signs, and monkeys with stable moderate or severe parkinsonism. DA was increased compared to controls, while neither NA and 5-HT nor the amino acid neurotransmitters were significantly changed. Furthermore, DA increased before stable motor deficits appear with +51% in asymptomatic and +96% in recovered monkeys. Unchanged DA metabolites suggest a special metabolic profile of the newly formed DA neurons. Significant correlation of homovanillic acid (HVA) with taurine single values within the four MPTP groups and of aspartate with taurine within the asymptomatic and recovered MPTP groups, but not within the controls suggest interactions in the OB between taurine and the DA system and taurine and the excitatory neurotransmitter triggered by MPTP. This first investigation of OB in various stages after MPTP administration suggests that the DA increase seems to be an early phenomenon, not requiring profound nigrostriatal neurodegeneration or PD symptoms., This work was funded by grants from the Ministerio de Economía y Competitividad: SAF2015-67239-P; Instituto de Salud Carlos III (CIBERNED) SAF2016-78207, Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III—Fondos FEDER, a way to build Europe FIS PIE14/00034 to JAO and by the chair UAM-Fundación Tatiana Pérez de Guzmán el Bueno to CC

We report on the neurological and neurophysiological findings obtained from two adult Macaca mulatta sustaining complete spinal cord transections at T8–T9. We performed periodic neurological exams, recorded motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS), and recorded electromyograms (EMGs) during the execution of a lower limb motor test. The main observations were: (1) the spinal shock period lasted less than a week; tendon, cutaneous and withdrawal reflexes were uneven in range and occurrence, and Babinski's sign was not observed; (2) a protracted functional lesion in the tibial and common peroneal nerves appeared bilaterally early in the post-lesional period; (3) MEPs were elicited by TMS in the quadriceps muscle of both monkeys; they were recorded as early as the 5th week after lesion in one of the monkeys, and they persisted throughout the post-lesional period in both monkeys; and (4) motor unit action potentials in the quadriceps muscle recorded by EMG were simultaneous with attempts to perform intentional lower limb movements from post-lesion month 11 to 13.5 in both monkeys. The last two sets of observations argue in favor of a partial cortico-spinal functional gain and suggest that spinal cord regeneration can occur after complete spinal cord injury in primates.

We recently identified the thalamic dopaminergic system in the human and macaque monkey brains, and, based on earlier reports on the paucity of dopamine in the rat thalamus, hypothesized that this dopaminergic system was particularly developed in primates. Here we test this hypothesis using immunohistochemistry against the dopamine transporter (DAT) in adult macaque and rat brains. The extent and density of DAT-immunoreactive (-ir) axons were remarkably greater in the macaque dorsal thalamus, where the mediodorsal association nucleus and the ventral motor nuclei held the densest immunolabeling. In contrast, sparse DAT immunolabeling was present in the rat dorsal thalamus; it was mainly located in the mediodorsal, paraventricular, ventral medial, and ventral lateral nuclei. The reticular nucleus, zona incerta, and lateral habenular nucleus held numerous DAT-ir axons in both species. Ultrastructural analysis in the macaque mediodorsal nucleus revealed that thalamic interneurons are a main postsynaptic target of DAT-ir axons; this suggests that the marked expansion of the dopamine innervation in the primate in comparison to the rodent thalamus may be related to the presence of a sizable interneuron population in primates. We remark that it is important to be aware of brain species differences when using animal models of human brain disease.

Classic and current parcellations of the posterior parietal cortex are reviewed. Whereas earlier studies relied on subjective observation of cortical cytoarchitecture, present parcellations are mostly based on connectional and physiological criteria. These criteria have led to the identification of five areas in the intraparietal sulcus with alleged visual function: VIP, MIP, PIP, AIP, and LIP. Other visual parietal areas are 7a, in the lateral parietal surface, and, in the medial parietal wall, 7m, and V6A. Present knowledge of the dimensions, boundaries, and connections of the various visual parietal areas is uneven: whereas LIP, 7a, and 7m have been extensively explored in anatomical and physiological studies, only scant information is available for most of the intraparietal areas. It is suggested that future studies address the anatomical and functional parcellation of the posterior parietal cortex using manifold objective means of study that allow comparison by independent researchers.

The Cavalieri method and the optical fractionator were employed to estimate the volume and neuron numbers, respectively, of the dorsal lateral geniculate nucleus (dLGN) in seven adult male pigtail monkeys (Macaca nemestrina). Unbiased estimates were selectively obtained for the parvocellular (P), magnocellular (M), and interlaminar plus superficial (I + S) layers of the nucleus. The dLGN had a mean volume of 56.5 mm3, and contained on average 1.79 million neurons. The P layers contributed 64% of the volume and 83% of the neurons in the dLGN; the corresponding proportions for the other layers were 13% and 9% (M), and 23% and 8% (I + S). Interindividual variability was large for neuron counts, which varied within a two-fold range, and lower for volume estimates. Since no published data are available for the pigtail dLGN, the present results are compared with quantitative studies of the dLGN in other macaque species, placing special emphasis in the discussion of the methodologies used.

The dorsal lateral geniculate nucleus of the thalamus (dLGN) projects to several extrastriate areas of the macaque brain. The extent of the dLGN projection to the visual temporal cortex was investigated using retrogradely transported dyes. A population of dLGN neurones was labelled after injections in the inferior temporal cortex (ITC) including the lower bank of the superior temporal sulcus and the inferior temporal convexity. The labelled neurons were located in the lateral half of the posterior one-third of the dLGN and predominated in the interlaminar zones or close to the borders of the parvocellular layers. This direct projection from the dLGN to the ITC may mediate some of the visual abilities known to be retained by destriated animals.

By 1889, at the age of 37 years, Cajal had published two papers on neuroanatomy in the Revista trimestral de Histologia normal y patologica, which he had founded (and subsidised) the previous year. However, his ideas received hardly any attention from his colleagues and he became a ‘little alarmed by their silence’ (Ramon y Cajal, 1981). He admitted that most histologists had not read his papers since ‘it is true that Spanish is an unknown language to the educated’ and he thought that the ‘direct objective demonstration’ of facts would be more convincing. Therefore, he first translated his principal papers into French and then decided to show his histological preparations to scientific colleagues, in order to demonstrate his findings and ideas. To this end, Cajal applied for membership of the Anatomische Gesellschaft, asked his Rector for permission to travel, collected all of his savings and set out for Berlin, where the Anatomische Gesellschaft met in October 1889.

We recently defined the thalamic dopaminergic system in primates; it arises from numerous dopaminergic cell groups and selectively targets numerous thalamic nuclei. Given the central position of the thalamus in subcortical and cortical interplay, and the functional relevance of dopamine neuromodulation in the brain, detailing dopamine distribution in the thalamus should supply important information. To this end we performed immunohistochemistry for dopamine and the dopamine transporter in the thalamus of macaque monkeys and humans to generate maps, in the stereotaxic coronal plane, of the distribution of dopaminergic axons. The dopamine innervation of the thalamus follows the same pattern in both species and is most dense in midline limbic nuclei, the mediodorsal and lateral posterior association nuclei, and in the ventral lateral and ventral anterior motor nuclei. This distribution suggests that thalamic dopamine has a prominent role in emotion, attention, cognition and complex somatosensory and visual processing, as well as in motor control. Most thalamic dopaminergic axons are thin and varicose and target both the neuropil and small blood vessels, suggesting that, besides neuronal modulation, thalamic dopamine may have a direct influence on microcirculation. The maps provided here should be a useful reference in future experimental and neuroimaging studies aiming at clarifying the role of the thalamic dopaminergic system in health and in conditions involving brain dopamine, including Parkinson’s disease, drug addiction and schizophrenia., This work was supported by Grants from the Ministerio de Ciencia y Tecnología and Ministerio de Educación of Spain (BFI2002-00513 and SAF2005-05380). B.R. and M.A.S.-G. were recipients of Fellowships from the Ministerio de Educación y Ciencia (B.R. and M.A.S.-G.) and from the Comunidad de Madrid (M.A.S.-G.).

Three series of double-labeling experiments were carried out in a study of the collateralization of brainstem nuclei which project to the spinal cord in the rat. The fluorescent tracer Diamidino Yellow Dihydrochloride (DY·2HCl) was injected in one half of the spinal gray and white matter at T7-T8 or T13-L1. Subsequently, either True Blue (TB), wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) or free HRP were injected ipsilaterally in the gray matter at C5–C8. The distributions of single and double retrogradely laabeled neurons were studied in the following cell groups: red nucleus, interstitial nucleus of Cajal, ventrolateral pontine tegmentum, nuclei coeruleus and subcoeruleus and nuclei raphe magnus and raphe pallidus including the adjoining ventral reticular formation. The numbers of TB- or HRP-labeled neurons present in those nuclei were counted and the percentages of double-labeled neurons were calculated when TB or HRP had been used in combination with DY·2HCl. The results indicate: (1) The HRP-TMB reaction product and the DY·2HCl fluorescence can be visualized simultaneously in retrogradely single- or double-labeled neurons. (2) The distributions of single- and double-labeled neurons in the various brainstem nuclei were entirely comparable when using TB with DY·2HCl or HRP with DY·2HCl. (3) The percentages of double-labeled neurons obtained with HRP and DY·2HCl were consistent over a series of cases, and were comparable to those obtained with TB and DY·2HCl in several structures. However, in the red nucleus slightly lower percentages of double-labeled neurons were obtained using HRP and DY·2HCl as compared with the percentages obtained using TB and DY·2HCl.

Following injections of horseradish peroxidase in area 20 of the cat neuronal labeling was observed in visual areas 19, 21 and lateral suprasylvian as well as in other sensory, association and limbic related neo- and allocortical regions, both ipsi- and contralaterally. Labeled neurons in the thalamus were identified in the LP-Pu complex, in the LIc, in the midline and intralaminar nuclei, and in the nuclei ventralis anterior, dorsalis medialis, lateralis anterior, lateralis medialis, ventralis posteroinferior, and in the medial subdivision of the posterior group. Projections from other subcortical prosencephalic and brainstem regions are also described.

The topographical distribution of the cortical afferent connections of the prefrontal cortex (PFC) in adult cats was studied by using the retrograde axonal transport of horseradish peroxidase technique. Small single injections of the enzyme were made in different locations of the PFC, and the areal location and density of the subsequent neuronal labeling in neocortex and allocortex were evaluated in each case. The comparison of the results obtained in the various cases revealed that (1) four prefrontal sectors (rostral, dorsolateral, ventral, and dorsomedial) can be distinguished, each exhibiting a particular pattern of cortical afferents. (2) All PFC sectors receive projections from the ipsilateral insular (agranular and granular subdivisions) and limbic (infralimbic, prelimbic, anterior limbic, cingular, and retrosplenial areas) cortices. These cortices provide the most abundant cortical projections to the PFC, and their various subdivisions have different preferential targets within the PFC. (3) The premotor cortex and the following neocortical sensory association areas project differentially upon the various ipsilateral PFC sectors: the portion of the somatosensory area SIV in the upper bank of the anterior ectosylvian sulcus, the visual area in the lower bank of the same sulcus, the auditory area AII, the temporal area, the perirhinal cortex, the posterior suprasylvian area, area 20, the posterior ectosylvian area, the suprasylvian fringe, the lateral suprasylvian area (anterolateral and posterolateral subdivisions), area 5, and area 7. (4) The olfactory peduncle, the prepiriform cortex, the cortico-amygdaloid transition area, the entorhinal cortex, the subiculum (ventral, posteroventral, and posterodorsal sectors), the caudomedial band off the hippocampal formation and the postsubiculum are the allocortical sources of afferents to the PFC. (5) The dorsolateral PFC sector is the target of the largest insular, limbic, and neocortical sensory association projections. The dorsomedial and rostral sectors receive notably less abundant cortical afferents than the dorsolateral sector. Those to the dorsomedial sector arise from the same areas that project to the dorsolateral sector and are more abundant to the dorsal part, where the medial frontal eye field cortex is located. The rostral sector receives projections principally from all other PFC sectors, and from the limbic and insular cortices. The projections from the allocortex reach preferentially the ventral PFC sector. (6) Intraprefrontal connections are most abundant within each PFC sector. Commissural interprefrontal connections are largest from the site homotopic to the HRP injection. Contralateral heterotopic areas also project to the PFC. The present findings are compared to the patterns of distribution of cortical afferents in the PFC reported in macaque monkeys and similarities and differences are considered.

We have examined the circuitry connecting the posterior parietal cortex with the frontal lobe of rhesus monkeys. HRP-WGA and tritiated amino acids were injected into subdivisions 7m, 7a, 7b, and 7ip of the posterior parietal cortex, and anterograde and retrograde label was recorded within the frontal motor and association cortices. Our main finding is that each subdivision of parietal cortex is connected with a unique set of frontal areas. Thus, area 7m, on the medial parietal surface, is interconnected with the dorsal premotor cortex and the supplementary motor area, including the supplementary eye field. Within the prefrontal cortex, area 7m's connections are with the rostral sector of the frontal eye field (FEF), the dorsal bank of the principal sulcus, and the anterior bank of the inferior arcuate sulcus (Walker's area 45). In contrast, area 7a, on the posterior parietal convexity, is not linked with premotor regions but is heavily interconnected with the rostral FEF in the anterior bank of the superior arcuate sulcus, the dorsolateral prefrontal convexity, the rostral orbitofrontal cortex, area 45, and the fundus and adjacent cortex of the dorsal and ventral banks of the principal sulcus. Area 7b, in the anterior part of the posterior parietal lobule, is interconnected with still a different set of frontal areas, which include the ventral premotor cortex and supplementary motor area, area 45, and the external part of the ventral bank of the principal sulcus. The prominent connections of area 7ip, in the posterior bank of the intraparietal sulcus, are with the supplementary eye field and restricted portions of the ventral premotor cortex, with a wide area of the FEF that includes both its rostral and caudal sectors, and with area 45. All frontoparietal connections are reciprocal, and although they are most prominent within a hemisphere, notable interhemispheric connections are also present. These findings provide a basis for a parcellation of the classically considered association cortex of the frontal lobe, particularly the cortex of the principal sulcus, into sectors defined by their specific connections with the posterior parietal subdivisions. Moreover, the present findings, together with those of a companion study (Cavada and Goldman-Rakic: J. Comp. Neurol. this issue) have allowed us to establish multiple linkages between frontal areas and specific limbic and sensory cortices through the posterior parietal cortex. The networks thus defined may form part of the neural substrate of parallel distributed processing in the cerebral cortex.

Afferent connections of the prefrontal cortex of the cat arising in allocortical regions have been investigated using the horseradish peroxidase retrograde transport technique. Our results demonstrate the existence of projections from the olfactory peduncle, anterior and posterior prepiriform cortices, cortico-amygdaloid transition area, entorhinal cortex, ventral, caudal and dorsal subiculum and postsubiculum to the prefrontal cortex.

Injections of HRP-WGA in four cytoarchitectonic subdivisions of the posterior parietal cortex in rhesus monkeys allowed us to examine the major limbic and sensory afferent and efferent connections of each area. Area 7a (the caudal part of the posterior parietal lobe) is reciprocally interconnected with multiple visual-related areas: the superior temporal polysensory area (STP) in the upper bank of the superior temporal sulcus (STS), visual motion areas in the upper bank of STS, the dorsal prelunate gyrus, and portions of V2 and the parieto-occipital (PO) area. Area 7a is also heavily interconnected with limbic areas: the ventral posterior cingulate cortex, agranular retrosplenial cortex, caudomedial lobule, the parahippocampal gyrus, and the presubiculum. By contrast, the adjacent subdivision, area 7ip (within the posterior bank of the intraparietal sulcus), has few limbic connections but projects to and receives projections from widespread visual areas different than those that are connected with area 7a: the ventral bank and fundus of the STS including part of the STP cortex and the inferotemporal cortex (IT), areas MT (middle temporal) and possibly MTp (MT peripheral) and FST (fundal superior temporal) and portions of V2, V3v, V3d, V3A, V4, PO, and the inferior temporal (IT) convexity cortex. The connections between posterior parietal areas and visual areas located on the medial surface of the occipital and parieto-occipital cortex, containing peripheral representations of the visual field (V2, V3, PO), represent a major previously unrecognized source of visual inputs to the parietal association cortex. Area 7b (the rostral part of the posterior parietal lobe) was distinctive among parietal areas in its selective association with somatosensory-related areas: S1, S2, 5, the vestibular cortex, the insular cortex, and the supplementary somatosensory area (SSA). Like 7ip, area 7b had few limbic associations. Area 7m (on the medial posterior parietal cortex) has its own topographically distinct connections with the limbic (the posterior ventral bank of the cingulate sulcus, granular retrosplenial cortex, and presubiculum), visual (V2, PO, and the visual motion cortex in the upper bank of the STS), and somatosensory (SSA, and area 5) cortical areas. Each parietal subdivision is extensively interconnected with areas of the contralateral hemisphere, including both the homotopic cortex and widespread heterotopic areas. Indeed, each area is interconnected with as many areas of the contralateral hemisphere as it is within the ipsilateral one, though less intensively. This pattern of distribution allows for a remarkable degree of interhemispheric integration. These findings provide evidence that each major subdivision of posteriorparietal cortex has a unique set of reciprocal connections with limbic and sen-sory areas in both hemispheres. For the most part, each parietalsubdivision, rather than being a site of multimodal convergence, receives input from only one sensory modality, though often from different channels of information within that modality. For example, the two streams of visual information tra-ditionally linked to pattern and motion seem to converge in both areas 7a and 7ip. The areal parcellation of parietal cortex byits afferent and efferent con-nections provides an anatomical foundation for a parallel processing model of higher cortical functions.

Ipsilateral cortical projections to the prefrontal cortex of the cat were investigated by means of the retrograde axonal transport of horseradish peroxidase technique. Labeled neurons were identified in frontal, insular, parietal and temporal regions, as well as in cingular, retrosplenial and perirhinal areas. These intrahemispheric cortical connections can be compared to those described in the rhesus monkey.