In vitro modeling of the human dopaminergic system using spatially arranged ventral midbrain-striatum-cortex assembloids.

Ventral midbrain dopaminergic neurons project to the striatum as well as the cortex and are involved in movement control and reward-related cognition. In Parkinson's disease, nigrostriatal midbrain dopaminergic neurons degenerate and cause typical Parkinson's disease motor-related impairments, while the dysfunction of mesocorticolimbic midbrain dopaminergic neurons is implicated in addiction and neuropsychiatric disorders. Study of the development and selective neurodegeneration of the human dopaminergic system, however, has been limited due to the lack of an appropriate model and access to human material. Here, we have developed a human in vitro model that recapitulates key aspects of dopaminergic innervation of the striatum and cortex. These spatially arranged ventral midbrain-striatum-cortical organoids (MISCOs) can be used to study dopaminergic neuron maturation, innervation and function with implications for cell therapy and addiction research. We detail protocols for growing ventral midbrain, striatal and cortical organoids and describe how they fuse in a linear manner when placed in custom embedding molds. We report the formation of functional long-range dopaminergic connections to striatal and cortical tissues in MISCOs, and show that injected, ventral midbrain-patterned progenitors can mature and innervate the tissue. Using these assembloids, we examine dopaminergic circuit perturbations and show that chronic cocaine treatment causes long-lasting morphological, functional and transcriptional changes that persist upon drug withdrawal. Thus, our method opens new avenues to investigate human dopaminergic cell transplantation and circuitry reconstruction as well as the effect of drugs on the human dopaminergic system.

Comparative morphology and morphometry of the mesencephalic tectum in the African giant rat (Cricetomys gambianus).

The caudal colliculus serves as an integrative station and switchboard, controlling nucleus of lower auditory pathway and motor-auditory reflex production. The rostral colliculus coordinates reflexive movement of the head, neck, eye and focus the lens for visual tracking of objects. There is no information comparing mesencephalic tectum among neonates, juveniles and adults of African giant rat (AGR). Hence, this study aimed to compare the gross features and morphometric parameters of mesencephalic tectum postnatally in AGR. The following were found and reported: (a) Paired dorsal tips of caudal colliculi were observed through transverse fissure of the intact brain and so, corpora quadrigemina were partly occluded by cerebral cortex in neonates and juveniles. (b) The lateral and medial geniculate bodies were visible, though the lateral was grossly bigger than the medial in adults and juveniles but,  only the lateral was distinguishable in neonates. (c) Live body weight, absolute brain weight, caudal colliculus width, nose-rump and tail lengths increased as AGRs developed with age; mean values of rostral colliculus weight, caudal colliculus height and weight of caudal colliculus in neonates and juveniles were statistically same; while midbrain weight and rostral colliculus height tends to decrease as rats aged. (d) The mean weight of caudal colliculi and width of rostral colliculi were not affected by age. (e) Caudal colliculi were grossly wider than rostral in juveniles and adults, but not neonates. Established regression formulae are necessary to avoid future sacrifice of this rodent.

Stria medullaris innervation follows the transcriptomic division of the habenula.

The habenula is a complex neuronal population integrated in a pivotal functional position into the vertebrate limbic system. Its main afference is the stria medullaris and its main efference the fasciculus retroflexus. This neuronal complex is composed by two main components, the medial and lateral habenula. Transcriptomic and single cell RNAseq studies have unveiled the morphological complexity of both components. The aim of our work was to analyze the relation between the origin of the axonal fibers and their final distribution in the habenula. We analyzed 754 tracing experiments from Mouse Brain Connectivity Atlas, Allen Brain Map databases, and selected 12 neuronal populations projecting into the habenular territory. Our analysis demonstrated that the projections into the medial habenula discriminate between the different subnuclei and are generally originated in the septal territory. The innervation of the lateral habenula displayed instead a less restricted distribution from preoptic, terminal hypothalamic and peduncular nuclei. Only the lateral oval subnucleus of the lateral habenula presented a specific innervation from the dorsal entopeduncular nucleus. Our results unveiled the necessity of novel sorts of behavioral experiments to dissect the different functions associated with the habenular complex and their correlation with the distinct neuronal populations that generate them.

Multi-omic landscaping of human midbrains identifies disease-relevant molecular targets and pathways in advanced-stage Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder whose prevalence is rapidly increasing worldwide. The molecular mechanisms underpinning the pathophysiology of sporadic PD remain incompletely understood. Therefore, causative therapies are still elusive. To obtain a more integrative view of disease-mediated alterations, we investigated the molecular landscape of PD in human post-mortem midbrains, a region that is highly affected during the disease process. METHODS: Tissue from 19 PD patients and 12 controls were obtained from the Parkinson's UK Brain Bank and subjected to multi-omic analyses: small and total RNA sequencing was performed on an Illumina's HiSeq4000, while proteomics experiments were performed in a hybrid triple quadrupole-time of flight mass spectrometer (TripleTOF5600+) following quantitative sequential window acquisition of all theoretical mass spectra. Differential expression analyses were performed with customized frameworks based on DESeq2 (for RNA sequencing) and with Perseus v.1.5.6.0 (for proteomics). Custom pipelines in R were used for integrative studies. RESULTS: Our analyses revealed multiple deregulated molecular targets linked to known disease mechanisms in PD as well as to novel processes. We have identified and experimentally validated (quantitative real-time polymerase chain reaction/western blotting) several PD-deregulated molecular candidates, including miR-539-3p, miR-376a-5p, miR-218-5p and miR-369-3p, the valid miRNA-mRNA interacting pairs miR-218-5p/RAB6C and miR-369-3p/GTF2H3, as well as multiple proteins, such as CHI3L1, HSPA1B, FNIP2 and TH. Vertical integration of multi-omic analyses allowed validating disease-mediated alterations across different molecular layers. Next to the identification of individual molecular targets in all explored omics layers, functional annotation of differentially expressed molecules showed an enrichment of pathways related to neuroinflammation, mitochondrial dysfunction and defects in synaptic function. CONCLUSIONS: This comprehensive assessment of PD-affected and control human midbrains revealed multiple molecular targets and networks that are relevant to the disease mechanism of advanced PD. The integrative analyses of multiple omics layers underscore the importance of neuroinflammation, immune response activation, mitochondrial and synaptic dysfunction as putative therapeutic targets for advanced PD.

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

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

Functional diversity for body actions in the mesencephalic locomotor region.

The mesencephalic locomotor region (MLR) is a key midbrain center with roles in locomotion. Despite extensive studies and clinical trials aimed at therapy-resistant Parkinson's disease (PD), debate on its function remains. Here, we reveal the existence of functionally diverse neuronal populations with distinct roles in control of body movements. We identify two spatially intermingled glutamatergic populations separable by axonal projections, mouse genetics, neuronal activity profiles, and motor functions. Most spinally projecting MLR neurons encoded the full-body behavior rearing. Loss- and gain-of-function optogenetic perturbation experiments establish a function for these neurons in controlling body extension. In contrast, Rbp4-transgene-positive MLR neurons project in an ascending direction to basal ganglia, preferentially encode the forelimb behaviors handling and grooming, and exhibit a role in modulating movement. Thus, the MLR contains glutamatergic neuronal subpopulations stratified by projection target exhibiting roles in action control not restricted to locomotion.

Subsystem macroarchitecture of the intrinsic midbrain neural network and its tectal and tegmental subnetworks.

The midbrain is the smallest of three primary vertebrate brain divisions. Here we use network science tools to reveal the global organizing principles of intramidbrain axonal circuitry before adding extrinsic connections with the remaining nervous system. Curating the experimental neuroanatomical literature yielded 17,248 connection reports for 8,742 possible connections between the 94 gray matter regions forming the right and left midbrain. Evidence for the existence of 1,676 connections suggests a 19.2% connection density for this network, similar to that for the intraforebrain network [L. W. Swanson et al., Proc. Natl. Acad. Sci. U.S.A. 117, 31470-31481 (2020)]. Multiresolution consensus cluster analysis parceled this network into a hierarchy with 6 top-level and 30 bottom-level subsystems. A structure-function model of the hierarchy identifies midbrain subsystems that play specific functional roles in sensory-motor mechanisms, motivation and reward, regulating complex reproductive and agonistic behaviors, and behavioral state control. The intramidbrain network also contains four bilateral region pairs designated putative hubs. One pair contains the superior colliculi of the tectum, well known for participation in visual sensory-motor mechanisms, and the other three pairs form spatially compact right and left units (the ventral tegmental area, retrorubral area, and midbrain reticular nucleus) in the tegmentum that are implicated in motivation and reward mechanisms. Based on the core hypothesis that subsystems form functionally cohesive units, the results provide a theoretical framework for hypothesis-driven experimental analysis of neural circuit mechanisms underlying behavioral responses mediated in part by the midbrain.

Folic acid supplementation rescues valproic acid-induced developmental neurotoxicity and behavioral alterations in zebrafish embryos.

OBJECTIVE: Fetal exposure to the anticonvulsant drug valproic acid (VPA), used to treat certain types of epilepsy, increases the risk for birth defects, including neural tube defects, as well as learning difficulties and behavioral problems. Here, we investigated neurotoxic effects of VPA exposure using zebrafish as a model organism. The capacity of folic acid (FA) supplementation to rescue the VPA-induced neuronal and behavioral perturbations was also examined. METHODS: Zebrafish embryos of different transgenic lines with neuronal green fluorescent protein expression were exposed to increasing concentrations of VPA with or without FA supplementation. Fluorescence microscopy was used to visualize alterations in brain structures and neural progenitor cells, as well as motor neurons and neurite sprouting. A twitching behavioral assay was used to examine the functional consequences of VPA and FA treatment. RESULTS: In zebrafish embryos, VPA exposure caused a decrease in the midbrain size, an increase in the midline gap of the hindbrain, and perturbed neurite sprouting of secondary motor neurons, in a concentration-dependent manner. VPA exposure also decreased the fluorescence intensity of neuronal progenitor cells in early developmental stages, indicating fewer cells. Furthermore, VPA exposure significantly altered embryonic twitching activity, causing hyperactivity in dark and hypoactivity in light. Supplementation of FA rescued the VPA-induced smaller midbrain size and hindbrain midline gap defects. FA treatment also increased the number of neuronal progenitor cells in VPA-treated embryos and salvaged neurite sprouting of the secondary motor neurons. FA rescued the VPA-induced alterations in twitching activity in light but not in dark. SIGNIFICANCE: We conclude that VPA exposure induces specific neurotoxic perturbations in developing zebrafish embryos, and that FA reversed most of the identified defects. The results demonstrate that zebrafish is a promising model to study VPA-induced teratogenesis and to screen for countermeasures.

The Paramedian Supracerebellar Approach: A Less Disruptive and More Flexible Operative Corridor to the Pineal and Posterior Upper Brainstem Regions.

The paramedian supracerebellar craniotomy is an underrecognized route to the midline and paramedian regions of the upper posterior brainstem. As compared with its midline supracerebellar counterpart, this less disruptive approach preserves the majority of the midline bridging veins, requires less cerebellar retraction, and is significantly more efficient. In this offering, I will emphasize the realities of this flexible route and its remarkable advantages in reaching deep-seated lesions.

Neuroanatomy of the spinosaurid Irritator challengeri (Dinosauria: Theropoda) indicates potential adaptations for piscivory.

Spinosauridae, a theropod group characterized by elongated snouts, conical teeth, enlarged forelimbs, and often elongated neural spines, show evidence for semiaquatic adaptations and piscivory. It is currently debated if these animals represent terrestrial carnivores with adaptations for a piscivorous diet, or if they largely lived and foraged in aquatic habitats. The holotype of Irritator challengeri, a nearly complete skull from the late Early Cretaceous Santana Formation of northeastern Brazil, includes one of the few preserved spinosaurid braincases and can provide insights into neuroanatomical structures that might be expected to reflect ecological affinities. We generated digital models of the neuroanatomical cavities within the braincase, using computer tomography (CT) data. The cranial endocast of Irritator is generally similar to that of other non-maniraptoriform theropods, with weakly developed distinctions of hindbrain and midbrain features, relatively pronounced cranial flexures and relatively long olfactory tracts. The endosseous labyrinth has a long anterior semicircular canal, a posteriorly inclined common crus and a very large floccular recess fills the area between the semicircular canals. These features indicate that Irritator had the ability for fast and well-controlled pitch-down head movements. The skull table and lateral semicircular canal plane are strongly angled to one another, suggesting a downward angling of approximately 45° of the snout, which reduces interference of the snout with the field of vision of Irritator. These neuroanatomical features are consistent with fast, downward snatching movements in the act of predation, such as are needed for piscivory.

Untangling the dorsal diencephalic conduction system: a review of structure and function of the stria medullaris, habenula and fasciculus retroflexus.

The often-overlooked dorsal diencephalic conduction system (DDCS) is a highly conserved pathway linking the basal forebrain and the monoaminergic brainstem. It consists of three key structures; the stria medullaris, the habenula and the fasciculus retroflexus. The first component of the DDCS, the stria medullaris, is a discrete bilateral tract composed of fibers from the basal forebrain that terminate in the triangular eminence of the stalk of the pineal gland, known as the habenula. The habenula acts as a relay hub where incoming signals from the stria medullaris are processed and subsequently relayed to the midbrain and hindbrain monoaminergic nuclei through the fasciculus retroflexus. As a result of its wide-ranging connections, the DDCS has recently been implicated in a wide range of behaviors related to reward processing, aversion and motivation. As such, an understanding of the structure and connections of the DDCS may help illuminate the pathophysiology of neuropsychiatric disorders such as depression, addiction and pain. This is the first review of all three components of the DDCS, the stria medullaris, the habenula and the fasciculus retroflexus, with particular focus on their anatomy, function and development.

Perineuronal nets and subtypes of GABAergic cells differentiate auditory and multisensory nuclei in the intercollicular area of the midbrain.

The intercollicular region, which lies between the inferior and superior colliculi in the midbrain, contains neurons that respond to auditory, visual, and somatosensory stimuli. Golgi studies have been used to parse this region into three distinct nuclei: the intercollicular tegmentum (ICt), the rostral pole of the inferior colliculus (ICrp), and the nucleus of the brachium of the IC (NBIC). Few reports have focused on these nuclei, especially the ICt and the ICrp, possibly due to lack of a marker that distinguishes these areas and is compatible with modern methods. Here, we found that staining for GABAergic cells and perineuronal nets differentiates these intercollicular nuclei in guinea pigs. Further, we found that the proportions of four subtypes of GABAergic cells differentiate intercollicular nuclei from each other and from adjacent inferior collicular subdivisions. Our results support earlier studies that suggest distinct morphology and functions for intercollicular nuclei, and provide staining methods that differentiate intercollicular nuclei and are compatible with most modern techniques. We hope that this will help future studies to further characterize the intercollicular region.

A neural ensemble correlation code for sound category identification.

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1-2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds.

Comparative morphology and histology of the brain in Chinese toad ( Bufo gargarizans ) and chinese fire-billed newt ( Cynops orientalis ) / Morfología e histología comparada del cerebro en el sapo chino ( Bufo gargarizans ) y el tritón vientre de fuego chino ( Cynops orientalis )

The morphological and histological structure of the brains of Bufo gargarizans and Cynops orientalis were observed by anatomy and light microscopy. The results show that the brains of Bufo gargarizans and Cynops orientalis are divided into 5 parts which include the telencephalon, diencephalon, mesencephalon, cerebellum and medulla oblongata. The telencephalon consists of the olfactory bulb and the cerebral hemisphere. The olfactory bulb is developed that has two pairs of olfactory nerve. Bufo gargarizan has a symmetrical oval hemisphere optic lobes; Cynops orientalis only has a spherical optic lobe. The cerebellum is situated behind the optic lobe and closely connected with the myelencephalon. In this paper, the morphological and histological differences between the two species are discussed. The proportion of cerebral hemisphere is gradually increasing, which correlated with a progressive increase in the number of neuronal cell classes, and reflected in behavior complexity.

La estructura morfológica e histológica de los cerebros de Bufo gargarizans y Cynops orientalis se observó mediante anatomía y microscopía óptica. Los resultados muestran que los cerebros de Bufo gargarizans y Cynops orientalis se dividen en 5 partes, que incluyen el telencéfalo, diencéfalo, mesencéfalo, cerebelo y mielencéfalo. El telencéfalo consiste en bulbo olfatorio y hemisferio cerebral. El bulbo olfatorio tiene dos pares de nervios olfatorios. Los lóbulos ópticos de Bufo gargarizans son ovalados y simétricos en ambos hemisferios cerebrales; Cynops orientalis tiene solo un lóbulo óptico esférico. El cerebelo está situado detrás del lóbulo óptico y está estrechamente conectado con el mielencéfalo. En este trabajo, se discuten las diferencias morfológicas e histológicas entre las dos especies. El tamaño del hemisferio cerebral aumenta gradualmente, lo que se correlaciona con un aumento progresivo de células neuronales en los núcleos, reflejándose en la complejidad del comportamiento.

Midbrain, Pons, and Medulla: Anatomy and Syndromes.

The anatomy of the brainstem is complex. It contains numerous cranial nerve nuclei and is traversed by multiple tracts between the brain and spinal cord. Improved MRI resolution now allows the radiologist to identify a higher level of anatomic detail, but an understanding of functional anatomy is crucial for correct interpretation of disease. Brainstem syndromes are most commonly due to occlusion of the posterior circulation or mass effect from intrinsic space-occupying lesions. These syndromes can have subtle imaging findings that may be missed by a radiologist unfamiliar with the anatomy or typical manifesting features. This article presents the developmental anatomy of the brainstem and discusses associated pathologic syndromes. Congenital and acquired syndromes are described and correlated with anatomic locations at imaging, with diagrams to provide a reference to aid in radiologic interpretation. ©RSNA, 2019.

Human brain transcriptome analysis finds region- and subject-specific expression signatures of GABAAR subunits.

Altered expression of GABA receptors (GABAARs) has been implicated in neurological and psychiatric disorders, but limited information about region-specific GABAAR subunit expression in healthy human brains, heteromeric assembly of major isoforms, and their collective organization across healthy individuals, are major roadblocks to understanding their role in non-physiological states. Here, by using microarray and RNA-Seq datasets-from single cell nuclei to global brain expression-from the Allen Institute, we find that transcriptional expression of GABAAR subunits is anatomically organized according to their neurodevelopmental origin. The data show a combination of complementary and mutually-exclusive expression patterns that delineate major isoforms, and which is highly stereotypical across brains from control donors. We summarize the region-specific signature of GABAR subunits per subject and its variability in a control population sample that can be used as a reference for remodeling changes during homeostatic rearrangements of GABAAR subunits after physiological, pharmacological or pathological challenges.

The Subtemporal Approach to the Lateral Midbrain with and without Zygomatic Osteotomy: An Anatomical Study.

The subtemporal approach provides a narrow operative corridor to the crus cerebrum and adjacent structures of the crural, interpeduncular, and ambient cistern. Addition of a zygomatic osteotomy widens this narrow corridor and spares retraction of the temporal lobe. We investigate and compare the morphometric parameters of the subtemporal approach with versus without zygomatic osteotomy. On each side of four cadaveric heads, a temporal craniotomy was performed to gain access to the crus cerebrum and adjacent subarachnoid cisterns using a subtemporal approach. Operative corridor width and corridor working angle were measured with and without brain retraction on each specimen side. Next, a zygomatic osteotomy was performed followed by full downward reflection of the temporalis muscle and further drilling of the squamous part of the temporal bone. Lastly, operative corridor width and corridor working angle were measured again for comparison. The subtemporal operating corridor was (mean/SD): 5.8/2.6 mm without retraction, 11.4/4.3 mm with retraction, and 13.5/6.5° working angle. After addition of a zygomatic osteotomy, the operative corridor was 8/9.2/4.3 mm without retraction, 14.7/4.5 mm with retraction, 31.8/3.1° working angle. Zygomatic osteotomy significantly increased the operative corridor working angle of the subtemporal approach. Furthermore, we demonstrate a direct approach into the interpeduncular fossa. Clin. Anat. 32:710-714, 2019. © 2019 Wiley Periodicals, Inc.

Environmental Influences on Neuromorphology in the Non-Native Starling Sturnus vulgaris.

Cognitive traits are predicted to be under intense selection in animals moving into new environments and may determine the success, or otherwise, of dispersal and invasions. In particular, spatial information related to resource distribution is an important determinant of neural development. Spatial information is predicted to vary for invasive species encountering novel environments. However, few studies have tested how cognition or neural development varies intraspecifically within an invasive species. In Australia, the non-native common starling Sturnus vulgaris inhabits a range of habitats that vary in seasonal resource availability and distribution. We aimed to identify variations in the brain mass and hippocampus volume of starlings in Australia related to environmental variation across two substantially different habitat types. Specifically, we predicted variation in brain mass and hippocampal volume in relation to environmental conditions, latitude, and climatic variables. To test this, brain mass and volumes of the hippocampus and two control brain regions (telencephalon and tractus septomesencephalicus) were quantified from starling brains gathered from across the species' range in south eastern Australia. When comparing across an environmental gradient, there was a significant interaction between sex and environment for overall brain mass, with greater sexual dimorphism in brain mass in inland populations compared to those at the coast. There was no significant difference in hippocampal volume in relation to environmental measures (hippocampus volume, n = 17) for either sex. While these data provide no evidence for intraspecific environmental drivers for changes in hippocampus volume in European starlings in Australia, they do suggest that environmental factors contribute to sex differences in brain mass. This study identifies associations between the brain volume of a non-native species and the environment; further work in this area is required to elucidate the mechanisms driving this relationship.

Parrots have evolved a primate-like telencephalic-midbrain-cerebellar circuit.

It is widely accepted that parrots show remarkable cognitive abilities. In mammals, the evolution of complex cognitive abilities is associated with increases in the size of the telencephalon and cerebellum as well as the pontine nuclei, which connect these two regions. Parrots have relatively large telencephalons that rival those of primates, but whether there are also evolutionary changes in their telencephalon-cerebellar relay nuclei is unknown. Like mammals, birds have two brainstem pontine nuclei that project to the cerebellum and receive projections from the telencephalon. Unlike mammals, birds also have a pretectal nucleus that connects the telencephalon with the cerebellum: the medial spiriform nucleus (SpM). We found that SpM, but not the pontine nuclei, is greatly enlarged in parrots and its relative size significantly correlated with the relative size of the telencephalon across all birds. This suggests that the telencephalon-SpM-cerebellar pathway of birds may play an analogous role to cortico-ponto-cerebellar pathways of mammals in controlling fine motor skills and complex cognitive processes. We conclude that SpM is key to understanding the role of telencephalon-cerebellar pathways in the evolution of complex cognitive abilities in birds.

In-vivo quantitative structural imaging of the human midbrain and the superior colliculus at 9.4T.

We explored anatomical details of the superior colliculus (SC) by in vivo magnetic resonance imaging (MRI) at 9.4T. The high signal-to-noise ratio allowed the acquisition of high resolution, multi-modal images with voxel sizes ranging between 176 × 132 × 600 µm and (800)3µm. Quantitative mapping of the longitudinal relaxation rate R1, the effective transverse relaxation rate R2*, and the magnetic susceptibility QSM was performed in 14 healthy volunteers. The images were analyzed in native space as well as after normalization to a common brain space (MNI). The coefficient-of-variation (CoV) across subjects was evaluated in prominent regions of the midbrain, reaching the best reproducibility (CoV of 5%) in the R2* maps of the SC in MNI space, while the CoV in the QSM maps remained high regardless of brain-space. To investigate whether more complex neurobiological architectural features could be detected, depth profiles through the SC layers towards the red nucleus (RN) were evaluated at different levels of the SC along the rostro-caudal axis. This analysis revealed alterations of the quantitative MRI parameters concordant with previous post mortem histology studies of the cyto- and myeloarchitecture of the SC. In general, the R1 maps were hyperintense in areas characterized by the presence of abundant myelinated fibers, and likely enabled detection of the deep white layer VII of the SC adjacent to the periaqueductal gray. While R1 maps failed to reveal finer details, possibly due to the relatively coarse spatial sampling used for this modality, these could be recovered in R2* maps and in QSM. In the central part of the SC along its rostro-caudal axis, increased R2* values and decreased susceptibility values were observed 2 mm below the SC surface, likely reflecting the myelinated fibers in the superficial optic layer (layer III). Towards the deeper layers, a second increase in R2* was paralleled by a paramagnetic shift in QSM suggesting the presence of an iron-rich layer about 3 mm below the surface of the SC, attributed to the intermediate gray layer (IV) composed of multipolar neurons. These results dovetail observations in histological specimens and animal studies and demonstrate that high-resolution multi-modal MRI at 9.4T can reveal several microstructural features of the SC in vivo.