Showing papers in "Brain Structure & Function in 2007"

Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat

Abstract: The medial prefrontal cortex (mPFC) has been associated with diverse functions including attentional processes, visceromotor activity, decision making, goal directed behavior, and working memory. Using retrograde tracing techniques, we examined, compared, and contrasted afferent projections to the four divisions of the mPFC in the rat: the medial (frontal) agranular (AGm), anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) cortices. Each division of the mPFC receives a unique set of afferent projections. There is a shift dorsoventrally along the mPFC from predominantly sensorimotor input to the dorsal mPFC (AGm and dorsal AC) to primarily 'limbic' input to the ventral mPFC (PL and IL). The AGm and dorsal AC receive afferent projections from widespread areas of the cortex (and associated thalamic nuclei) representing all sensory modalities. This information is presumably integrated at, and utilized by, the dorsal mPFC in goal directed actions. In contrast with the dorsal mPFC, the ventral mPFC receives significantly less cortical input overall and afferents from limbic as opposed to sensorimotor regions of cortex. The main sources of afferent projections to PL/IL are from the orbitomedial prefrontal, agranular insular, perirhinal and entorhinal cortices, the hippocampus, the claustrum, the medial basal forebrain, the basal nuclei of amygdala, the midline thalamus and monoaminergic nuclei of the brainstem. With a few exceptions, there are few projections from the hypothalamus to the dorsal or ventral mPFC. Accordingly, subcortical limbic information mainly reaches the mPFC via the midline thalamus and basal nuclei of amygdala. As discussed herein, based on patterns of afferent (as well as efferent) projections, PL is positioned to serve a direct role in cognitive functions homologous to dorsolateral PFC of primates, whereas IL appears to represent a visceromotor center homologous to the orbitomedial PFC of primates.

Do early sensory cortices integrate cross-modal information?

Abstract: Our different senses provide complementary evidence about the environment and their interaction often aids behavioral performance or alters the quality of the sensory percept A traditional view defers the merging of sensory information to higher association cortices, and posits that a large part of the brain can be reduced into a collection of unisensory systems that can be studied in isolation Recent studies, however, challenge this view and suggest that cross-modal interactions can already occur in areas hitherto regarded as unisensory We review results from functional imaging and electrophysiology exemplifying cross-modal interactions that occur early during the evoked response, and at the earliest stages of sensory cortical processing Although anatomical studies revealed several potential origins of these cross-modal influences, there is yet no clear relation between particular functional observations and specific anatomical connections In addition, our view on sensory integration at the neuronal level is coined by many studies on subcortical model systems of sensory integration; yet, the patterns of cross-modal interaction in cortex deviate from these model systems in several ways Consequently, future studies on cortical sensory integration need to leave the descriptive level and need to incorporate cross-modal influences into models of the organization of sensory processing Only then will we be able to determine whether early cross-modal interactions truly merit the label sensory integration, and how they increase a sensory system’s ability to scrutinize its environment and finally aid behavior

Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex

Abstract: A basic feature of the neocortex is its organization in functional, vertically oriented columns, recurring modules of signal processing and a system of transcolumnar long-range horizontal connections. These columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical columns contain thousands of neurons and span all cortical layers. They receive input from other cortical areas and subcortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a cortical column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of cortical signal processing and the underlying neuronal 'microcircuits'. In the last decade the 'barrel' field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a cortical column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a cortical column, with emphasis on excitatory signal flow.

Mapping functional connectivity in barrel-related columns reveals layer- and cell type-specific microcircuits.

Abstract: Synaptic circuits bind together functional modules of the neocortex. We aim to clarify in a rodent model how intra- and transcolumnar microcircuits in the barrel cortex are laid out to segregate and also integrate sensory information. The primary somatosensory (barrel) cortex of rodents is the ideal model system to study these issues because there, the tactile information derived from the large facial whiskers on the snout is mapped onto so called barrel-related columns which altogether form an isomorphic map of the sensory periphery. This allows to functionally interpret the synaptic microcircuits we have been analyzing in barrel-related columns by means of whole-cell recordings, biocytin filling and mapping of intracortical functional connectivity with sublaminar specificity by computer-controlled flash-release of glutamate. We find that excitatory spiny neurons (spiny stellate, star pyramidal, and pyramidal cells) show a layer-specific connectivity pattern on top of which further cell type-specific circuits can be distinguished. The main features are: (a) strong intralaminar, intracolumnar connections are established by all types of excitatory neurons with both, excitatory and (except for layer Vb- intrinsically burst-spiking-pyramidal cells) inhibitory cells; (b) effective translaminar, intracolumnar connections become more abundant along the three main layer compartments of the canonical microcircuit, and (c) extensive transcolumnar connectivity is preferentially found in specific cell types in each of the layer compartments of a barrel-related column. These multiple sequential and parallel circuits are likely to be suitable for specific cortical processing of "what" "where" and "when" aspects of tactile information acquired by the whiskers on the snout.

Three-dimensional reconstruction of the axon arbor of a CA3 pyramidal cell recorded and filled in vivo

Abstract: The three-dimensional intrahippocampal distribution of axon collaterals of an in vivo filled CA3c pyramidal cell was investigated. The neuron was filled with biocytin in an anesthetized rat and the collaterals were reconstructed with the aid of a NeuroLucida program from 48 coronal sections. The total length of the axon collaterals exceeded 0.5 m, with almost 40,000 synaptic boutons. The majority of the collaterals were present in the CA1 region (70.0%), whereas 27.6% constituted CA3 recurrent collaterals with the remaining minority of axons returning to the dentate gyrus. The axon arbor covered more than two thirds of the longitudinal axis of the hippocampus, and the terminals were randomly distributed both locally and distally from the soma. We suggest that the CA3 system can be conceptualized as a single-module, in which nearby and distant targets are contacted by the same probability (similar to a mathematically defined random graph). This arrangement, in combination with the parallel input granule cells and parallel output CA1 pyramidal cells, appears ideal for segregation and integration of information and memories.

Orienting and maintenance of spatial attention in audition and vision: multimodal and modality-specific brain activations

Abstract: We studied orienting and maintenance of spatial attention in audition and vision. Functional magnetic resonance imaging (fMRI) in nine healthy subjects revealed activations in the same superior and inferior parietal, and posterior prefrontal areas in the auditory and visual orienting tasks when these tasks were compared with the corresponding maintenance tasks. Attention-related activations in the thalamus and cerebellum were observed during the auditory orienting and maintenance tasks and during the visual orienting task. In addition to the supratemporal auditory cortices, auditory orienting, and maintenance produced stronger activity than the respective visual tasks in the inferior parietal and prefrontal cortices, whereas only the occipital visual cortex and the superior parietal cortex showed stronger activity during the visual tasks than during the auditory tasks. Differences between the brain networks involved in auditory and visual spatial attention could be, for example, due to different encoding of auditory and visual spatial information or differences in stimulus-driven (bottom-up triggered) and voluntary (top-down controlled) attention between the auditory and visual modalities, or both.

Development of the human fetal insular cortex: study of the gyration from 13 to 28 gestational weeks

Abstract: To describe the morphological stages of insular sulci and gyri development we carried out a macroscopical study on 21 human fetal brains, showing no anomalies, from 13 to 28 gestational weeks (GWs). Particular focus was given to morphological appearance during the development of insular and periinsular structures, especially the gyration and sulcation of the insula, central cerebral region and opercula, as well as the vascularization of these regions. The periinsular sulci and the central (insular and cerebral) sulci were the first macroscopical structures identified on the lateral surface of the human fetal cerebral hemisphere with earlier development on the right hemisphere. Here we describe five stages of insular gyral and sulcal development closely related to gestational age: stage 1: appearance of the first sulcus at 13-17 GWs, stage 2: development of the periinsular sulci at 18–19 GWs, stage 3: central sulci and opercularization of the insula at 20–22 GWs, stage 4: covering of the posterior insula at 24–26 GWs, stage 5: closure of the sylvian fissure at 27–28 GWs. We provide evidence that cortical maturation (sulcation and gyration) and vascularization of the lateral surface of the brain starts with the insular region, suggesting that this region is a central area of cortical development.

Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex

Abstract: Newly generated neurons are continuously added to the olfactory epithelium and olfactory bulbs of adult mammals. Studies also report newly generated neurons in the piriform cortex, the primary cortical projection site of the olfactory bulbs. The current study used BrdU-injection paradigms, and in vivo and in vitro DiI tracing methods to address three fundamental issues of these cells: their origin, migratory route and fate. The results show that 1 day after a BrdU-injection, BrdU/DCX double-labeled cells appear deep to the ventricular subependyma, within the white matter. Such cells appear further ventral and caudal in the ensuing days, first appearing in the rostral piriform cortex of mice at 2 days after the BrdU-injection, and at 4 days in the rat. In the caudal piriform cortex, BrdU/DCX labeled cells first appear at 4 days after the injection in mice and 7 days in rats. The time it takes for these cells to appear in the piriform cortex and the temporal distribution pattern suggest that they migrate from outside this region. DiI tracing methods confirmed a migratory route to the piriform cortex from the ventricular subependyma. The presence of BrdU/NeuN labeled cells as early as 7 days after a BrdU injection in mice and 10 days in the rat and lasting as long as 41 days indicates that some of these cells have extended survival durations in the adult piriform cortex.

Laminar distribution and co-distribution of neurotransmitter receptors in early human visual cortex.

Abstract: The laminar distributions of 16 neurotransmitter receptor binding sites were analysed in visual cortical areas V1–V3 by quantitative in vitro receptor autoradiography. For each receptor (glutamatergic: AMPA, kainate, NMDA; cholinergic: M1, M2, M3, nicotinic; GABAergic: GABAA, GABAB, benzodiazepine binding-sites; adrenergic: α1, α2; serotoninergic: 5-HT1A, 5-HT2; dopaminergic: D1; Adenosine: A1), density profiles extracted perpendicular to the cortical surface were compared to cyto- and myeloarchitectonic profiles sampled at corresponding cortical sites. When testing for differences in laminar distribution patterns, all receptor-density profiles differed significantly from the cyto- and myeloarchitectonic ones. These results indicate that receptor distribution is an independent feature of the cortical architecture not predictable by densities of cell bodies or myelinated fibres. Receptor co-distribution was studied by cluster analyses, revealing several groups of receptors, which showed similar laminar distribution patterns across all analysed areas (V1–V3). Other receptors were co-distributed in extrastriate but not primary visual cortex. Finally, some receptors were not co-distributed with any of the analysed other ones. A comparison of the laminar patterns of receptor binding sites in the human visual cortex with those reported for non-human primates and other mammals showed that the laminar distributions of cholinergic and glutamatergic receptors seem largely preserved, while serotoninergic and adrenergic receptors appear to be more variable between different species.

Multimodal architectonic subdivision of the caudal ventrolateral prefrontal cortex of the macaque monkey

Abstract: The caudal part of the macaque ventrolateral prefrontal cortex (VLPF) is part of several functionally distinct domains. In the present study we combined a cyto- and a myeloarchitectonic approach with a chemoarchitectonic approach based on the distribution of SMI-32 and Calbindin immunoreactivity, to determine the number and extent of architectonically distinct areas occupying this region. Several architectonically distinct areas, completely or partially located in the caudal VLPF, were identified. Two areas are almost completely limited to the anterior bank of the inferior arcuate sulcus, a dorsal one—8/FEF—which extends also more dorsally and should represent the architectonic counterpart of the frontal eye field, and a ventral one—45B—which occupies the ventral half of the bank. Two other areas occupy the ventral prearcuate convexity cortex, a caudal one—area 8r—located just rostral to area 8/FEF and a rostral one—area 45A—which extends as far as the inferior frontal sulcus. Area 45A borders dorsally, in the proximity of the principal sulcus, with area 46 and, ventrally, with area 12. The present data show the existence of two distinct prearcuate convexity areas (8r and 45A), extending other architectonic subdivisions of the caudal VLPF and providing a new, multiarchitectonic frame of reference for this region. The present architectonic data, together with other functional and connectional data, suggest that areas 8/FEF, 45B and 8r are part of the oculomotor frontal cortex, while area 45A is a distinct entity of the VLPF domain involved in high-order processing of nonspatial information.

Mitochondrial degeneration in dystrophic neurites of senile plaques may lead to extracellular deposition of fine filaments

Abstract: Recent data show that amyloid precursor protein accumulates inside axons after disruption of fast axonal transport, but how this leads to mature plaques with extracellular amyloid remains unclear. To investigate this issue, primitive plaques in prefrontal cortex of aged rhesus monkeys were reconstructed using serial section electron microscopy. The swollen profiles of dystrophic neurites were found to be diverticula from the main axis of otherwise normal neurites. Microtubules extended from the main neurite axis into the diverticulum to form circular loops or coils, providing a transport pathway for trapping organelles. The quantity and morphology of organelles contained within diverticula suggested a progression of degeneration. Primitive diverticula contained microtubules and normal mitochondria, while larger, presumably older, diverticula contained large numbers of degenerating mitochondria. In advanced stages of degeneration, apparent autophagosomes derived from mitochondria exhibited a loose lamellar to filamentous internal structure. Similar filamentous material and remnants of mitochondria were visible in the extracellular spaces of plaques. This progression of degeneration suggests that extracellular filaments originate inside degenerating mitochondria of neuritic diverticula, which may be a common process in diverse diseases.

Comparative analysis of extra-ventricular mitoses at early stages of cortical development in rat and human

Abstract: Embryonic germinal zones of the dorsal and ventral telencephalon generate cortical neurons during the final week of gestation in rodent and during several months in human. Whereas the vast majority of cortical interneurons originate from the ventral telencephalon, excitatory neurons are locally generated within the germinal zone of the dorsal telencephalon, the future cerebral cortex, itself. However, a number of studies have described proliferating cells external to the ventricular and subventricular germinal zones in the developing dorsal telencephalon. In this study, we performed a comprehensive cell density analysis of such ‘extra-ventricular proliferating cells’ (EVPCs) during corticogenesis in rat and human using a mitotic marker anti-phospho-histone H3. Subsequently, we performed double-labelling studies with other mitotic and cell type specific markers to undertake phenotypic characterisation of EVPCs. Our findings show: (1) the densities of extra-ventricular H3-positive (H3+) cells were surprisingly similar in preplate stage rat and human; (2) extra-ventricular proliferation continues during mid-and late corticogenesis in rat and in early fetal human cortex; and (3) extra-ventricular cells appear to be mitotic precursors as they are not immunoreactive for a panel of early post-mitotic and cell type-specific markers, although (4) a subset of EVPCs are proliferating microglia. These data suggest that some aspects of early corticogenesis are conserved between rodent and human despite marked differences in the duration of neurogenesis and the anatomical organisation of the developing cerebral cortex.

Morphological characterization of electrophysiologically and immunohistochemically identified basal forebrain cholinergic and neuropeptide Y-containing neurons.

Abstract: The basal forebrain (BF) contains cholinergic as well as different types of non-cholinergic corticopetal neurons and interneurons, including neuropeptide Y (NPY) containing cells. BF corticopetal neurons constitute an extrathalamic route to the cortex and their activity is associated with an increase in cortical release of the neurotransmitter acetylcholine, concomitant with low voltage fast cortical EEG activity. It has been shown in previous studies (Duque et al. in J Neurophysiol 84:1627–1635, 2000) that in anesthetized rats BF cholinergic neurons fire mostly during low voltage fast cortical EEG epochs, while increased NPY neuronal firing is accompanied by cortical slow waves. In this paper, electrophysiologically and neurochemically characterized cholinergic and NPY-containing neurons were 3D reconstructed from serial sections and morphometrically analyzed. Cholinergic and NPY-containing neurons, although having roughly the same dendritic surface areas and lengths, were found to differ in dendritic thickness and branching structure. They also have distinct patterns of dendritic endings. The subtle differences in dendritic arborization pattern may have an impact on how synaptic integration takes place in these functionally distinct neuronal populations. Cholinergic neurons exhibited cortically projecting axons and extensive local axon collaterals. Elaborate local axonal arbors confined to the BF also originated from NPY-containing neurons. The presence of local axon collaterals in both cholinergic and NPY neurons indicates that the BF is not a mere conduit for various brainstem inputs to the cortex, but a site where substantial local processing must take place.

Local origin and activity-dependent generation of nestin-expressing protoplasmic astrocytes in CA1

Abstract: Since reports that precursor cells in the adult subventricular zone (SVZ) contribute to regenerative neuro- and gliogenesis in CA1, we wondered whether a similar route of migration might also exist under physiological conditions. Permanent labeling of SVZ precursor cells with a lentiviral vector for green fluorescent protein did not reveal any migration from the SVZ into CA1 in the intact murine brain. However, in a nestin-GFP reporter mouse we found proliferating cells within the corpus callosum/alveus region expressing nestin and glial fibrillary acidic protein similar to precursor cells in the neighboring neurogenic region of the adult dentate gyrus. Within 3 weeks of BrdU administration, BrdU-positive nestin-GFP-expressing protoplasmic astrocytes emerged in CA1. Similar to precursor cells isolated from the dentate gyrus and the SVZ, nestin-GFP-expressing cells from corpus callosum/alveus were self-renewing and multipotent in vitro, whereas cells isolated from CA1 were not. Nestin-GFP-expressing cells in CA1 differentiated into postmitotic astrocytes characterized by S100beta expression. No new neurons were found in CA1. The number of nestin-GFP-expressing astrocytes in CA1 was increased by environmental enrichment. We conclude that astrogenesis in CA1 is influenced by environmental conditions. However, SVZ precursor cells do not contribute to physiological cellular plasticity in CA1.

Modality-independent involvement of the left BA 44 during lexical decision making

Abstract: During a lexical decision task, lexical decision making can be distinguished from lexical retrieval. Lexical decision making is independent of stimulus modality and not reflected in the decision times, whereas the opposite holds for lexical retrieval. In neuroimaging studies investigating lexical decision tasks with either visual or auditory stimuli these two processes have so far been confused. Therefore, it is not clear whether the activation of Broca’s region, consisting of the left Brodmann’s area (BA) 44 and BA 45, reported in such studies really reflects lexical decision making. The present event-related fMRI study investigated the role of Broca’s region in lexical decision by analyzing brain activation that is independent of stimulus modality or decision times. Twenty-two healthy participants performed lexical decisions on visual and auditory real words and pseudo-words. The left BA 44 was conjointly activated during visual and auditory lexical decisions as compared to rest indicating the modality-independent involvement of BA 44 in lexical decision tasks in general. To identify brain activation related to lexical decision making rather than lexical retrieval the decision times were entered as covariates into the fMRI analysis. In this analysis, the left BA 44 was activated for visual and for auditory lexical decision making. These results indicate that the left BA 44 as a distinct sub-part of Broca’s region plays an important role in lexical decision making independently of stimulus modality and decision times.

A detailed 3D model of the guinea pig cochlea

Abstract: Several partial models of cochlear subparts are available. However, a complete 3D model of an intact cochlea based on actual histological sections has not been reported. Hence, the aim of this study was to develop a novel 3D model of the guinea pig cochlea and conduct post-processes on this reconstructed model. We used a combination of histochemical processing and the method of acquiring section data from the visible human project (VHP) to obtain a set of ideal raw images of cochlear sections. After semi-automatic registration and accurate manual segmentation with professional image processing software, one set of aligned data and six sets of segmented data were generated. Finally, the segmented structures were reconstructed by 3D Slicer (a professional imaging process and analysis tool). Further, post-processes including 3D visualization and a virtual endoscope were completed to improve visualization and simulate the course of the cochlear implant through the scala tympani. The 3D cochlea model contains the main six structures: (1) the inner wall, (2) modiolus and spiral lamina, (3) cochlea nerve and spiral ganglion, (4) spiral ligament and inferior wall of cochlear duct, (5) Reissner's membrane and (6) tectorial membrane. Based on the results, we concluded that ideal raw images of cochlear sections can be acquired by combining the processes of conventional histochemistry and photographing while slicing. After several vital image processing and analysis steps, this could further generate a vivid 3D model of the intact cochlea complete with internal details. This novel 3D model has great potential in teaching, basic medical research and in several clinical applications.

Bottom-up and top-down brain functional connectivity underlying comprehension of everyday visual action.

Abstract: How can the components of visual comprehension be characterized as brain activity? Making sense of a dynamic visual world involves perceiving streams of activity as discrete units such as eating breakfast or walking the dog. In order to parse activity into distinct events, the brain relies on both the perceptual (bottom-up) data available in the stimulus as well as on expectations about the course of the activity based on previous experience with, or knowledge about, similar types of activity (top-down data). Using fMRI, we examined the contribution of bottom-up and top-down processing to the comprehension of action streams by contrasting familiar action sequences with those having exactly the same perceptual detection and motor responses (yoked control), but no visual action familiarity. New methods incorporating structural equation modeling of the data yielded distinct patterns of interactivity among brain areas as a function of the degree to which bottom-up and top-down data were available.

Coexpression of vesicular glutamate transporters 1 and 2, glutamic acid decarboxylase and calretinin in rat entorhinal cortex

Abstract: We studied the distribution and coexpression of vesicular glutamate transporters (VGluT1, VGluT2), glutamic acid decarboxylase (GAD) and calretinin (CR, calcium-binding protein) in rat entorhinal cortex, using immunofluorescence staining and multichannel confocal laser scanning microscopy. Images were computer processed and subjected to automated 3D object recognition, colocalization analysis and 3D reconstruction. Since the VGluTs (in contrast to CR and GAD) occurred in fibers and axon terminals only, we focused our attention on these neuronal processes. An intense, punctate VGluT1-staining occurred everywhere in the entorhinal cortex. Our computer program resolved these punctae as small 3D objects. Also VGluT2 showed a punctate immunostaining pattern, yet with half the number of 3D objects per tissue volume compared with VGluT1, and with statistically significantly larger 3D objects. Both VGluTs were distributed homogeneously across cortical layers, with in MEA VGluT1 slightly more densely distributed than in LEA. The distribution pattern and the size distribution of GAD 3D objects resembled that of VGluT2. CR-immunopositive fibers were abundant in all cortical layers. In double-stained sections we noted ample colocalization of CR and VGluT2, whereas coexpression of CR and VGluT1 was nearly absent. Also in triple-staining experiments (VGluT2, GAD and CR combined) we noted coexpression of VGluT2 and CR and, in addition, frequent coexpression of GAD and CR. Modest colocalization occurred of VGluT2 and GAD, and incidental colocalization of all three markers. We conclude that the CR-containing axon terminals in the entorhinal cortex belong to at least two subpopulations of CR-neurons: a glutamatergic excitatory and a GABAergic inhibitory.

A proposal for MRI-based parcellation of the frontal pole

Abstract: The frontal pole (FP), which largely overlaps with Brodmann’s area (BA) 10, is the rostral-most part of the hominid cerebral cortex, and plays a critical role in complex aspects of human cognition. The existing conventions suggested for MRI-based parcellation of this important frontal subdivision have limited cytoarchitectonic meaning with regard to the demarcation of the FP from adjacent prefrontal subdivisions. In this paper, we propose the coronal section containing the anterior termination of the olfactory sulcus (ATOS) as an easy-to-identify landmark for FP parcellation that largely overlaps with the cytoarchitectonic distinction between BA 10 and the more posterior cytoarchitectonic subdivisions of the PFC. Manual segmentation-based parcellation of the FP using the proposed landmark in 20 healthy volunteers yielded highly reliable (standardized item alpha = 0.92) volumetric estimates [right FP volume = 8.421 cm3 (SE = 0.773, range 3.107–15.741); left FP volume = 8.039 cm3 (SE = 0.708, range 2.234–12.956)]. The volumetric measurements of right FP generated in the present study were comparable to those reported in a prior study of BA 10 using histological sections and stereological techniques (Semendeferi et al. In: Am J Phys Anthropol 114:224–241, 2001). Therefore, in the absence of a naturally occurring sulcal boundary, the proposed method for parcellation of the FP can provide unbiased volume estimations for studies of healthy and disordered populations of subjects.

Branching of individual somatosensory cerebropontine axons in rat: evidence of divergence

Abstract: The cerebral cortex conveys major input to the granule cell layer of the cerebellar hemispheres by way of the pontine nuclei. Cerebrocortical projections terminate in multiple, widely distributed clusters in the pontine nuclei. This clustered organization is thought to provide the transition between the different organizational principles of the cerebrum and cerebellum, and indicates that parallel processing occurs at multiple sites in the pontine nuclei. At a cellular level, however, it is unknown whether individual cerebropontine neurons target pontocerebellar cells located in different clusters or not. We have employed anterograde axonal tracing and 3D computerized reconstruction techniques to characterize the branching pattern and morphology of individual cerebropontine axons from the primary somatosensory cortex (SI). Our findings show that 43% of the cerebrobulbar fibers arising from SI whisker representations provide two or three fibers entering the pontine nuclei, whereas 39% have only one fiber, and the remaining 18% do not project to the pontine nuclei. Thus, it appears that a majority of cerebropontine axons originating in SI whisker representations diverge to contact multiple, separated pontocerebellar cells. Further, 84% of the somatosensory cerebropontine fibers are collateral branches from cerebrobulbar and/or cerebrospinal parent fibers, while 16% are direct cerebropontine projections without a further descending projection. A range of thicknesses of the fibers entering the pontine nuclei were observed, with collaterals of corticobulbar fibers having the smallest diameter. Taken together, these findings may be related to previously described separate cerebropontine transmission lines with different properties.

Purkinje cell age-distribution in fissures and in foliar crowns: a comparative study in the weaver cerebellum

Abstract: Generation and settling of Purkinje cells (PCs) are investigated in the weaver mouse cerebellum in order to determine possible relationships with the fissuration pattern. Tritiated thymidine was supplied to pregnant females at the time that these neurons were being produced. Autoradiography was then applied on brain sections obtained from control and weaver offspring at postnatal (P) day 90. This makes it possible to assess the differential survival of neurons born at distinct embryonic times on the basis of the proportion of labeled cells located at the two foliar compartments: fissures and foliar crowns. Our data show that throughout the surface contour of the vermal lobes, generative programs of PCs were close between wild type and homozygous weaver. Similar data were found in the lobules of the lateral hemisphere. On the other hand, the loss of PCs in weaver cerebella can be related to foliar concavities or convexities depending on the vermal lobe or the hemispheric lobule studied. Lastly, we have obtained evidence that late-generated PCs of both normal and mutant mice were preferentially located in fissures. These quantitative relationships lead us to propose a model in which the final distribution of PCs through the vermal contour would be coupled to two factors: the cortical fissuration patterning and a “time-sequential effect” of weaver mutation.

Precerebellar and vestibular nuclei of the short-beaked echidna (Tachyglossus aculeatus).

Abstract: The monotremes are a unique group of living mammals, which diverged from the line leading to placental mammals at least 125 million years ago. We have examined the organization of pontine, inferior olivary, lateral reticular and vestibular nuclei in the brainstem of the short-beaked echidna (Tachyglossus aculeatus) to determine if the cyto- and chemoarchitecture of these nuclei are similar to that in placental mammals and marsupials. We have used Nissl staining in conjunction with enzyme-histochemistry for acetylcholinesterase, cytochrome oxidase and NADPH diaphorase as well as immunohistochemistry for non-phosphorylated neurofilament protein (SMI-32 antibody) and calcium binding proteins (parvalbumin, calbindin, calretinin). Homologies could be established between the arch shaped inferior olivary complex of the echidna and the principal, dorsal and medial accessory subdivisions of the therian inferior olivary complex. The pontine nuclei of the echidna included basilar and reticulotegmental components with similar cyto- and chemarchitectural features to therians and there were magnocellular and subtrigeminal components of the lateral reticular nucleus, also as seen in therians. Subdivisions and chemoarchitecture of the vestibular complex of the echidna were both similar to that region in rodents. In all three precerebellar nuclear groups studied and in the vestibular nucleus organization, the cyto- and chemoarchitecture of the echidna was very similar to that seen in therian mammals and no "primitive" or "reptilian" features were evident.

The effect of vestibular nerve section on the expression of the hyaluronan in the frog, Rana esculenta.

Abstract: Following postganglionic lesion of the eighth cranial nerve, the changes in the expression of hyaluronan (HA), one of the extracellular matrix macromolecules, were examined in the medial (MVN) and lateral (LVN) vestibular nuclei and in the entry or transitional zone (TZ) of the nerve in the frog. HA was detected in different survival times by using a specific biotinylated hyaluronan-binding probe. HA expression was defined by the area-integrated optical density (AIOD), calculated from pixel intensities of digitally captured images. During the first postoperative days the perineuronal net (PN), a HA-rich area around the neurons, was not distinguishable from the surrounding neuropil in the MVN and LVN, characterized by a bilateral drop of AIOD specifically on the operated side. From postoperative day 14 onwards AIOD increased whilst the PN reorganized. In contrast, the AIOD wobbled up and down bilaterally without any trend in the TZ. Statistical analysis indicated that AIOD changes in the structures studied ran parallel bilaterally presumably because of the operation. Our results demonstrated for the first time that (1) the lesion of the eighth cranial nerve is accompanied by the modification of AIOD reflected HA expression in the MVN, LVN and TZ, (2) different tendencies exist in the time course of AIOD in the structures studied and (3) these tendencies are similar on the intact and operated sides. Our findings may suggest an area dependent molecular mechanism of HA in the restoration of vestibular function.

The pretectal nuclei in two monotremes: the short-beaked echidna ( Tachyglossus aculeatus ) and the platypus ( Ornithorhynchus anatinus )

Abstract: We have examined the organization of the pretectal area in two monotremes (the short beaked echidna—Tachyglossus aculeatus, and the platypus—Ornithorhynchus anatinus) and compared it to that in the Wistar strain rat, using Nissl staining in conjunction with enzyme histochemistry (acetylcholinesterase and NADPH diaphorase) and immunohistochemistry for parvalbumin, calbindin, calretinin and non-phosphorylated neurofilament protein (SMI-32 antibody). We were able to identify distinct anterior, medial, posterior (now called tectal gray) and olivary pretectal nuclei as well as a nucleus of the optic tract, all with largely similar topographical and chemoarchitectonic features to the homologous regions in therian mammals. The positions of these pretectal nuclei correspond to the distributions of retinofugal terminals identified by other authors. The overall size of the pretectum in both monotremes was found to be at least comparable in size, if not larger than, the pretectum of representative therian mammals of similar brain and body size. Our findings suggest that the pretectum of these two monotreme species is comparable in both size and organization to that of eutherian mammals, and is more than just an undifferentiated area pretectalis. The presence of a differentiated pretectum with similar chemoarchitecture to therians in both living monotremes lends support to the idea that the stem mammal for both prototherian and therian lineages also had a differentiated pretectum. This in turn indicates that a differentiated pretectum appeared at least 125 million years ago in the mammalian lineage and that the stem mammal for proto- and eutherian lineages probably had similar pretectal nuclei to those identified in its descendants.