Joan S. Baizer

Organization of visual inputs to the inferior temporal and posterior parietal cortex in macaques

It has been proposed that visual information in the extrastriate cortex is conveyed along 2 major processing pathways, a “dorsal” pathway directed to the posterior parietal cortex, underlying spatial vision, and a “ventral” pathway directed to the inferior temporal cortex, underlying object vision. To determine the relative distributions of cells projecting to the 2 pathways, we injected the posterior parietal and inferior temporal cortex with different fluorescent tracers in 5 rhesus monkeys. The parietal injections included the ventral intraparietal (VIP) and lateral intraparietal (LIP) areas, and the temporal injections included the lateral portions of cytoarchitectonic areas TE and TEO. There was a remarkable segregation of cells projecting to the 2 systems. Inputs to the parietal cortex tended to arise either from areas that have been implicated in spatial or motion analysis or from peripheral field representations in the prestriate cortex. By contrast, inputs to the temporal cortex tended to arise from areas that have been implicated in form and color analysis or from central field representations. Cells projecting to the parietal cortex were found in visual area 2 (V2), but only in the far peripheral representations of both the upper and lower visual field. Likewise, labeled cells found in visual areas 3 (V3) and 4 (V4) were densest in their peripheral representations. Heavy accumulations of labeled cells were found in the dorsal parieto-occipital cortex, including the parieto-occipital (PO) area, part A of V3 (V3A), and the dorsal prelunate area (DP). In the superior temporal sulcus, cells were found within several motion-sensitive areas, including the middle temporal area (MT), the medial superior temporal area (MST), the fundus of the superior temporal area (FST), and the superior temporal polysensory area (STP), as well as within anterior portions of the sulcus whose organization is as yet poorly defined. Cells projecting to areas TE and TEO in the temporal cortex were located within cytoarchitectonic area TG at the temporal pole and cytoarchitectonic areas TF and TH on the parahippocampal gyrus, as well as in noninjected portions of area TE buried within the superior temporal sulcus. In the prestriate cortex, labeled cells were found in V2, V3, and V4, but, in contrast to the loci labeled after parietal injections, those labeled after temporal injections were concentrated in the foveal or central field representations. Although few double-labeled cells were seen, 2 regions containing intermingled parietal- and temporal-projection cells were area V4 and the cortex at the bottom of the anterior superior temporal sulcus.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of subcortical connections of inferior temporal and posterior parietal cortex in monkeys.

To investigate the subcortical connections of the object vision and spatial vision cortical processing pathways, we injected the inferior temporal and posterior parietal cortex of six Rhesus monkeys with retrograde or anterograde tracers. The temporal injections included area TE on the lateral surface of the hemisphere and adjacent portions of area TEO. The parietal injections covered the posterior bank of the intraparietal sulcus, including areas VIP and LIP. Our results indicate that several structures project to both the temporal and parietal cortex, including the medial and lateral pulvinar, claustrum, and nucleus basalis. However, the cells in both the pulvinar and claustrum that project to the two systems are mainly located in different parts of those structures, as are the terminals which arise from the temporal and parietal cortex. Likewise, the projections from the temporal and parietal cortex to the caudate nucleus and putamen are largely segregated. Finally, we found projections to the pons and superior colliculus from parietal but not temporal cortex, whereas we found the lateral basal and medial basal nuclei of the amygdala to be reciprocally connected with temporal but not parietal cortex. Thus, the results show that, like the cortical connections of the two visual processing systems, the subcortical connections are remarkably segregated.

The transcription factor Nfix is essential for normal brain development

BackgroundThe Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects; Nfib-deficient mice have defects in lung maturation and show callosal agenesis and forebrain defects resembling those seen in Nfia-deficient animals, while Nfic-deficient mice have defects in tooth root formation. Recently the Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix-deficient mice.ResultsHere we show that disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development that differ from those seen in Nfia and Nfib KO mice. In particular, complete callosal agenesis is not seen in Nfix-/- mice but rather there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. On standard lab chow Nfix-/- animals show a decreased growth rate from ~P8 to P14, lose weight from ~P14 to P22 and die at ~P22. If their food is supplemented with a soft dough chow from P10, Nfix-/- animals show a lag in weight gain from P8 to P20 but then increase their growth rate. A fraction of the animals survive to adulthood and are fertile. The weight loss correlates with delayed eye and ear canal opening and suggests a delay in the development of several epithelial structures in Nfix-/- animals.ConclusionThese data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.

Bilateral projections from the parabigeminal nucleus to the superior colliculus in monkey

SummaryWe examined the distribution of labeled neurons in the parabigeminal nucleus of the monkey following injections of retrograde fluorescent tracers into the superior colliculus. The extent of the visual field representation included in the injection site was assessed from the location of labeled cells in striate cortex. The results suggest a rough topographic organization of the parabigeminal nucleus, with the lower quadrant represented anteriorly and the upper quadrant posteriorly. We also found bilateral projections from the parabigeminal nucleus to both superior colliculi, but the crossed projection appeared to terminate only in that part of the colliculus where the vertical meridian is represented. Parabigeminal cells with a crossed projection were larger than those projecting to the ipsilateral colliculus. The results suggest that the organization of the monkeys parabigemino-tectal system is fundamentally similar to that of many other vertebrates.

Independent roles for the dorsal paraflocculus and vermal lobule VII of the cerebellum in visuomotor coordination.

Two distinct areas of cerebellar cortex, vermal lobule VII and the dorsal paraflocculus (DPFl) receive visual input. To help understand the visuomotor functions of these two regions, we compared their afferent and efferent connections using the tracers wheatgerm agglutinin horseradish peroxidase (WGA-HRP) and biotinilated dextran amine (BDA). The sources of both mossy fibre and climbing fibre input to the two areas are different. The main mossy fibre input to lobule VII is from the nucleus reticularis tegmenti pontis (NRTP), which relays visual information from the superior colliculus, while the main mossy fibre input to the DPFl is from the pontine nuclei, relaying information from cortical visual areas. The DPFl and lobule VII both also receive mossy fibre input from several common brainstem regions, but from different subsets of cells. These include visual input from the dorsolateral pons, and vestibular–oculomotor input from the medial vestibular nucleus (MVe) and the nucleus prepositus hypoglossi (Nph). The climbing fibre input to the two cerebellar regions is from different subdivisions of the inferior olivary nuclei. Climbing fibres from the caudal medial accessory olive (cMAO) project to lobule VII, while the rostral MAO (rMAO) and the principal olive (PO) project to the DPFl. The efferent projections from lobule VII and the DPF1 are to all of the recognised oculomotor and visual areas within the deep cerebellar nuclei, but to separate territories. Both regions play a role in eye movement control. The DPFl may also have a role in visually guided reaching.

Comparison of saccadic eye movements in humans and macaques to single-step and double-step target movements

Human and monkey saccade amplitude and latency, in response to 12-36 degrees target steps, differed substantially despite nearly identical experimental conditions. On single-step trials, monkeys did not undershoot targets, and latencies were insensitive to stimulus and contextual factors. Human saccades did undershoot, their latency was longer, and both undershoot and latency were affected by stimulus variables and experimental context. On double-step trials, the second target step altered primary saccade amplitude when the step occurred as little as 40 msec prior to saccade onset for both humans and monkeys. However, humans and monkeys showed somewhat different amplitude transition functions, and monkeys showed little evidence of parallel programming.

IMMUNOREACTIVITY FOR CALCIUM-BINDING PROTEINS IN THE CLAUSTRUM OF THE MONKEY

 The claustrum is topographically and reciprocally connected with many different cortical areas, and anatomical and physiological data suggest it is composed of functionally distinct subdivisions. We asked if the distribution of cells immunoreactive for three calcium-binding proteins, parvalbumin, calbindin D-28k and calretinin would delineate functional subdivisions in the claustrum. We also asked if, as in cortex, different cell types were immunoreactive for the different proteins. We found that cells with parvalbumin-ir were large, multipolar cells. Cells immunoreactive for calretinin were bipolar cells with elongated cell bodies and beaded dendrites. There were three different types of cells immunoreactive for calbindin. The most numerous were small cells with round or oval cell bodies and numerous fine, winding processes. A second type were large multipolar, cells that resembled the parvalbumin-ir cells. The third class were bipolar cells with large, elongated cell bodies. Each type of cell resembles a cell type described in earlier Golgi studies, and each has a morphological cortical counterpart. While the different cell types varied in density, each was seen over the anterior-posterior and dorsal-ventral extent of the claustrum.

Immunoreactivity for calcium-binding proteins defines subregions of the vestibular nuclear complex of the cat

The vestibular nuclear complex (VNC) is classically divided into four nuclei on the basis of cytoarchitectonics. However, anatomical data on the distribution of afferents to the VNC and the distribution of cells of origin of different efferent pathways suggest a more complex internal organization. Immunoreactivity for calcium-binding proteins has proven useful in many areas of the brain for revealing structure not visible with cell, fiber or Golgi stains. We have looked at the VNC of the cat using immunoreactivity for the calcium-binding proteins calbindin, calretinin and parvalbumin. Immunoreactivity for calretinin revealed a small, intensely stained region of cell bodies and processes just beneath the fourth ventricle in the medial vestibular nucleus. A presumably homologous region has been described in rodents. The calretinin-immunoreactive cells in this region were also immunoreactive for choline acetyltransferase. Evidence from other studies suggests that the calretinin region contributes to pathways involved in eye movement modulation but not generation. There were focal dense regions of fibers immunoreactive to calbindin in the medial and inferior nuclei, with an especially dense region of label at the border of the medial nucleus and the nucleus prepositus hypoglossi. There is anatomical evidence that suggests that the likely source of these calbindin-immunoreactive fibers is the flocculus of the cerebellum. The distribution of calbindin-immunoreactive fibers in the lateral and superior nuclei was much more uniform. Immunoreactivity to parvalbumin was widespread in fibers distributed throughout the VNC. The results suggest that neurochemical techniques may help to reveal the internal complexity in VNC organization.

The human dentate nucleus: a complex shape untangled

The dentate nucleus is the largest single structure linking the cerebellum to the rest of the brain. The peculiar shape and large size of the human dentate nucleus have sparked a number of theories about the role of the cerebellum in human evolution. Some of the proposed ideas could be explored by comparative studies of humans and apes, but comparative studies are hindered because of the complex three dimensional shape of the human dentate. Here we present a 3D model based on a quantitative reconstruction of the human dentate; this model can facilitate comparative studies. The dentate nucleus has been partitioned into dorsal and ventral lamellae based on sheet thickness. Our data show that the thicker ventral lamella occupies a distinctly smaller portion of the human dentate than previously hypothesized. Within the dorsal lamella there is a medial to lateral increase in depth of dentate folds. However, the dorsal lamella retains a thin sheet thickness unlike the macrogyric ventral lamella, in which sheet thickness is increased. The appearance of larger folds laterally reflects the emergence of secondary folds that could encompass the projection of the cerebellar hemispheres, minimizing convergence of different corticonuclear microzones. Thus, the unique feature of the hominoid dentate is the development of a large surface area and an expansion of its mediolateral width. We propose that this is to allow for a large number of independent corticonuclear modules that can modulate an equal large number of sequential motor acts.

Serotonergic innervation of the primate claustrum

The claustrum is reciprocally and topographically connected with all functional areas of the cerebral cortex. Different cortical areas differ in the source, density, and laminar distribution of serotonergic innervation, with visual cortex receiving an especially rich serotonergic innervation. We asked if there were likewise differences in serotonergic innervation in different regions of the claustrum. We analyzed 50-microm coronal sections through the claustrum of the macaque monkey processed using standard immunohistochemical techniques and an antibody to serotonin. We found labeled fibers throughout the dorsal-ventral and anterior-posterior extent of the claustrum. A few fibers were relatively straight and lacked varicosities. Most fibers had varicosities; the size, shape, and spacing of varicosities varied among fibers and even along a single fiber. Some stained fibers partially encircled cells, and varicosities were seen in close apposition to the cell bodies. There was a major difference between dorsal and ventral claustrum in the pattern of stained fibers. In the ventral, visual, claustrum, stained segments of axons were short and randomly arranged relative to each other, and there were many stained puncta. In the more dorsal, nonvisual claustrum, many fibers ran in a dorsal-ventral direction, along the long axis of the claustrum, and could be followed for long distances.