Identification of differentially expressed genes in the visual structures of brain using high-density cDNA grids

The hybridization patterns of 18,371 high-density-grid-arrayed non-redundant complementary DNA (cDNA) clones were examined using three different sources of cDNA probes. The first set of probes was synthesized from mRNA isolated from visual brain areas MT and V4 of Vervet monkey. The second set of probes was derived from cDNA libraries constructed from two micro dissected sets of layers of the monkey Lateral Geniculate Nucleus layers within the visual pathway, namely the magnocellular and parvocellular layers. The third set of cDNA probes was synthesized from the subtracted fractions of the cDNAs enriched for either the magnocellular or the parvocellular layers of the Lateral Geniculate Nucleus. Software, linked directly to the Genbank database, was developed to aid in the rapid identification of both expressed and differentially expressed genes. Our results indicate that both the cDNA probes synthesized from mRNA and cDNA libraries can identify similar fractions of expressed genes. However, the subtracted cDNA probes improve the efficiency of detection for those genes that are expressed at much lower abundance. Analyses of these results for the differential expression patterns of these genes were validated by semi-quantitative PCR on the DNA derived from the whole tissue cDNA libraries. A list of some known genes that are statistically differentially expressed within the magnocellular layers of the LGN and area MT in the primate visual areas is derived.     

Does primate motion perception depend on the magnocellular pathway?

This study examined the importance of the primate magnocellular retinocortical pathway in the perception of moving stimuli. A portion of the magnocellular pathway was permanently and selectively interrupted by ibotenic acid injections in the LGN of macaque monkeys. We then tested contrast sensitivity for detecting moving stimuli, as well as two indices of motion perception, contrast sensitivity for opposite direction discrimination and speed difference thresholds, in the affected portion of the visual field. Magnocellular lesions greatly reduced detection contrast sensitivity at high temporal and low spatial frequencies and had a similar effect on contrast sensitivity for opposite direction discrimination under these same stimulus conditions. Consequently, opposite direction discriminations could be made at contrast threshold, suggesting that magnocellular lesions reduced the visibility of stimuli used to test direction perception, but did not act directly on direction perception. Magnocellular lesions also elevated speed difference thresholds under some stimulus conditions. However, this deficit was reduced or eliminated by raising the contrast of the test stimulus. Together, these findings suggest that magnocellular lesions reduce the visibility of stimuli used to test motion perception but that they do not appear to alter motion perception otherwise.     

Connections between layer 4B of area 17 and the thick cytochrome oxidase stripes of area 18 in the squirrel monkey

In area 18 of the primate visual cortex, staining for the mitochondrial enzyme cytochrome oxidase reveals 3 types of stripelike subdivisions running perpendicular to the 17/18 border: thick, thin, and pale stripes. In a previous paper (Livingstone and Hubel, 1984), we described the anatomical connections with area 17 of 2 of these 3 subdivisions, but we did not have any conclusive information on the third subdivision, the thick stripes. Here we report that, in the squirrel monkey, the main input to the thick stripes from area 17 arises from layer 4B. Layer 4B receives its input from the magnocellular division of the lateral geniculate body by way of layer 4C alpha; the thick stripes therefore probably belong to the magnocellular subdivision of the visual pathway.     

Magnocellular and parvocellular contributions to responses in the middle temporal visual area (MT) of the macaque monkey

Many lines of evidence suggest that the visual signals relayed through the magnocellular and parvocellular subdivisions of the primate dorsal LGN remain largely segregated through several levels of cortical processing. It has been suggested that this segregation persists through to the highest stages of the visual cortex, and that the pronounced differences between the neuronal response properties in the parietal cortex and inferotemporal cortex may be attributed to differential contributions from magnocellular and parvocellular signals. We have examined this hypothesis directly by recording the responses of cortical neurons while selectively blocking responses in the magnocellular or parvocellular layers of the LGN. Responses were recorded from single units or multiunit clusters in the middle temporal visual area (MT), which is part of the pathway leading to parietal cortex and thought to receive primarily magnocellular inputs. Responses in the MT were consistently reduced when the magnocellular subdivision of the LGN was inactivated. The reduction was almost always pronounced and often complete. In contrast, parvocellular block rarely produced striking changes in MT responses and typically had very little effect. Nevertheless, unequivocal parvocellular contributions could be demonstrated for a minority of MT responses. At a few MT sites, responses were recorded while magnocellular and parvocellular blocks were made simultaneously. Responses were essentially eliminated for all these paired blocks. These results provide direct evidence for segregation of magnocellular and parvocellular contributions in the extrastriate visual cortex and support the suggestion that these signals remain largely segregated through the highest levels of cortical processing.     

Neuronal classes and their relation to functional and laminar organization of the lateral geniculate nucleus: a Golgi study of the prosimian primate, Galago crassicaudatus

The neuronal organization of the lateral geniculate nucleus of the prosimian primate, Galago crassicaudatus, was studied in Golgi-Kopsch-impregnated material. On the basis of cytoarchitecture, electrophysiology, and connections the nucleus is divisible into three pairs of layers--one magnocellular, one parvocellular, and one koniocellular--each part of a separate retinogeniculate and geniculostriate pathway (Itoh et al., '82; Norton and Casagrande, '82). In Macaca and Saimiri, which have equally distinct geniculate subdivisions, it has been reported that, outside of cell size, no one morphological attribute differentiates magnocellular from parvocellular neurons (Campo-Ortega et al., '68; Wong-Riley, '72; Saini and Garey, '81; Wilson and Hendrickson, '81). Results presented here are not inconsistent with this conclusion. However, when the results are analyzed from the standpoint of the collective traits that distinguish the cell groups that make up the layers, clear morphological differences are evident. Using this approach we find the following differences between presumed projection neurons and interneurons in each pair of layers. The projection neurons of the magnocellular layers, as a group, exhibit large cell bodies with radially arranged dendrites which often extend beyond laminar borders. The magnocellular interneurons are larger than their counterparts in the other layers and, like the magnocellular projection neurons, exhibit radially arranged dendrites. The former, however, also share characteristics in common with other interneurons such as relatively small somata, few proximal dendrites, and complex distal dendritic appendages. In contrast, the projection neurons and interneurons of the parvocellular layers have smaller somata and more restricted dendritic spreads than their counterparts in the magnocellular layers. Dendritic arbors of parvocellular neurons are typically oriented perpendicular to laminar borders and remain confined to their layer of origin. The koniocellular neurons represent a more diverse population but collectively are distinct in that the dendrites of almost all neurons in these layers run parallel to the layers. The fact that presumed interneurons and projection neurons in a single layer share a number of related dendritic features suggests that both groups together are responsible for the structural and, hence, functional architecture of a layer.(ABSTRACT TRUNCATED AT 400 WORDS)     

Abnormal magnocellular pathway visual processing in infants at risk for autism.

BACKGROUND: A wealth of data has documented impairments in face processing in individuals with autism spectrum disorders (ASD). Recently, the suggestion has been made that these impairments may arise from abnormal development of a subcortical system involved in face processing that originates in the magnocellular pathway of the primate visual system. METHODS: To test this developmental hypothesis, we obtained visual perceptual data from 6-month-old infants who were at risk for ASD because they had an older sibling diagnosed with the disorder ("high-risk infants"). To measure sensitivity of the magnocellular (M) pathway and, for comparison, of the parvocellular (P) visual pathway, we employed visual stimuli designed to selectively stimulate the two. Sensitivity data from high-risk infants (n = 13) were compared with data from matched control infants (i.e., "low-risk" infants with no family history of ASD, n = 26). RESULTS: On the P pathway stimulus, high-risk infants exhibited sensitivities that were identical to those of control infants. By contrast, on the M pathway stimulus, high-risk infants exhibited sensitivities nearly twofold greater than those of control infants. CONCLUSIONS: Given that ASD and its symptoms are known to run in families, these preliminary results suggest that ASD may be associated with abnormal M pathway function early in infancy, which may aid in early diagnosis of the disorder.     

The distribution of cholinesterase and cytochrome oxidase within the dorsal lateral geniculate nucleus of the squirrel monkey

Within the dorsal lateral geniculate nucleus (dLGN) of the squirrel monkey, acetylcholinesterase (AChE) and cytochrome oxidase (CO) are distributed preferentially in the magnocellular layers. Butyrylcholinesterase (BuChE) activity is comparatively weak, but higher in the parvocellular than in the magnocellular layers. The different patterns of distribution of AChE within the dLGN in different primate species signify differences in geniculate organization, which may reflect adaptation to different visual habitats.     

Normal planum temporale asymmetry in dyslexics with a magnocellular pathway deficit

Developmental dyslexia has been associated with both abnormal hemispheric symmetry of the planum temporale (PT) and a deficit in the magnocellular visual pathway. We examined the relationship between these two abnormalities. Using sagittal magnetic resonance images and three methods, we measured the PT in dyslexic subjects with a documented magnocellular deficit and controls. Dyslexic subjects did not deviate from normal leftward PT asymmetry, but both groups became less left-lateralized with methods that excluded sulcul tissue. Results suggest that dyslexic subjects with a magnocellular deficit do not always have abnormal symmetry of the PT. PT symmetry may instead be related to a different subtype of dyslexia. In addition, PT asymmetry in any subject group depends on the measurement method.     

基因芯片检测难治性癫脑组织中sh3gl2的表达

目的：运用基因芯片和RT-PCR技术检测难治性癫脑组织中sh3gl2 mRNA表达,从分子水平探讨难治性癫可能的发病机制。方法：在应用基因芯片对难治性癫患者手术切除的颞叶组织与对照组行基因表达谱分析研究的基础上,筛选出目的基因后用RT-PCR对芯片扫描结果进行验证。结果：候选基因sh3gl2在难治性癫患者脑部颞叶组织中出现高表达,与对照组相比差异有显著统计学意义（P〈0.01）;RT-PCR结果与芯片结果一致。结论：sh3gl2在难治性癫颞叶皮质中的表达增加,提示了其可能是难治性癫发生发展中的一个重要因素。     

Vocal control pathways through the anterior forebrain of a parrot (Melopsittacus undulatus)

A feature of the telencephalic vocal control system in the budgerigar (Melopsittacus undulatus) that has been hypothesized to represent a profound difference in organization from the oscine vocal system is its reported lack of an inherent circuit through the anterior forebrain. The present study reports anatomical connections that indicate the existence of an anterior forebrain circuit comparable in important ways to the “recursive” pathway of oscine songbirds. Results from anterograde and retrograde tracing experiments with biocytin and fluorescently labeled dextran amines indicate that the central nucleus of the anterior archistriatum (AAc) is the source of ascending projections upon the oval nuclei of the anterior neostriatum and ventral hyperstriatum (NAo and HVo, respectively). Efferent projections from the latter nuclei terminate in the lateral neostriatum afferent to AAc, thereby forming a short recurrent pathway through the pallium. Previously reported projections from HVo and NAo upon the magnocellular nucleus of the lobus parolfactorius (LPOm), and from LPOm onto the magnocellular nucleus of the dorsal thalamus (DMm; G.F. Striedter [1994] J. Comp. Neurol. 343:35–56), are confirmed. A specific projection from DMm onto NAom is also demonstrated; therefore, a recurrent pathway through the basal forebrain also exists in the budgerigar vocal system that is similar to the anterior forebrain circuit of oscine songbirds. Parallels between these circuits and mammalian basal ganglia-thalamo-cortical circuits are discussed. It is hypothesized that vocal control nuclei of the avian anterior neostriatum may perform a function similar to the primate supplemental motor area. J. Comp. Neurol. 377:179–206, 1997. © 1997 Wiley-Liss, Inc.     

Specific retinotopically based magnocellular impairment in a patient with medial visual dorsal stream damage

We report here retinotopically based magnocellular deficits in a patient with a unilateral parieto-occipital lesion. We applied convergent methodologies to study his dorsal stream processing, using psychophysics as well as structural and functional imaging. Using standard perimetry we found deficits involving the periphery of the left inferior quadrant abutting the horizontal meridian, suggesting damage of dorsal retinotopic representations beyond V1. Retinotopic damage was much more extensive when probed with frequency-doubling based contrast sensitivity measurements, which isolate processing within the magnocellular pathway: sensitivity losses now encroached on the visual central representation and did not respect the horizontal meridian, suggesting further damage to dorsal stream retinotopic areas that contain full hemi-field representations, such as human V3A or V6. Functional imaging revealed normal responses of human MT+ to motion contrast. Taken together, these findings are consistent with a recent proposal of two distinct magnocellular dorsal stream pathways: a latero-dorsal pathway passing to MT+ and concerned with the processing of coherent motion, and a medio-dorsal pathway that routes information from V3A to the human homologue of V6. Anatomical evidence was consistent with sparing of the latero-dorsal pathway in our patient, and was corroborated by his normal performance in speed, direction discrimination and motion coherence tasks with 2D and 3D objects. His pattern of dysfunction suggests damage only to the medio-dorsal pathway, an inference that is consistent with structural imaging data, which revealed a lesion encompassing the right parieto-occipital sulcus.     

The neuroanatomical organization of pathways between the dorsal lateral geniculate nucleus and visual cortex in Old World and New World primates.

Pathways between the dorsal lateral geniculate nucleus (dLGN) and visual cortex in Old World (Macaca, Papio, Erythrocebus, Cercopithecus) and New World (Saimiri, Cebus) primates were studied after injections of horseradish peroxidase and H3 or S35 amino acids into the dLGN or visual cortex. Trans-synaptic autoradiography was also used to study these pathways after an injection of H3 proline-fucose into one eye. The subsequent autoradiographs of visual cortex showed that Old World primates have separate eye inputs (ocular dominance columns) in the striate cortex, whereas New World monkeys have overlapping or non-separated eye inputs. In both primate groups the geniculocortical input to layer IVA formed a pattern which resembled a honeycomb in tangential sections, unlike the solidly labeled layer IVC. Also common to the two primate groups was a projection from dLGN to layer VI. There was no dLGN projection to any prestriate area in any of the primates. However, after an injection limited to the prestriate cortex of Macaca, light autoradiographic labeling was seen in the interlaminar zones and the magnocellular and S laminae, demonstrating a prestriate-dLGN pathway. Our results indicate that the primate visual system differs significantly from the cat in having no dLGN projection to area 18. There are also signficant differences between primates in the level at which the possibility of binocularity (of an excitatory nature) first occurs in the striate cortex because in the species studied thus far with neuroanatomical methods, Old World primates have ocular dominance columns in layer IV but most New World monkeys lack them.     

Differential inhibition of chromatic and achromatic perception by transcranial magnetic stimulation of the human visual cortex.

The magnocellular visual pathway is devoted to low-contrast achromatic and motion perception whereas the parvocellular pathway deals with chromatic and high resolution spatial vision. To specifically separate perception mediated by these pathways we have used low-contrast Gaussian filtered black-white or coloured visual stimuli. By use of transcranial magnetic stimulation (TMS) over the visual cortex inhibition of magnocellular stimuli was achieved distinctly earlier by about 40 ms compared with parvocellular information. A nonspecific inhibition of all stimuli could be seen peaking at 75-90 ms, significantly higher for magnocellular stimuli. The particular vulnerability of magnocellular stimuli to TMS is correlated with distinct physiological properties of this pathway such as faster conduction velocity and non-linear stimulus encoding.     

Stereologic analysis of the lateral geniculate nucleus of the thalamus in normal and schizophrenic subjects

Reduction of volume and neuronal number has been found in several association nuclei of the thalamus in schizophrenic subjects. Recent evidence suggests that schizophrenic patients exhibit abnormalities in early visual processing and that many of the observed perceptual deficits are consistent with dysfunction of the magnocellular pathway, i.e. the visual relay from peripheral retinal cells to the two ventrally located magnocellular layers of the lateral geniculate nucleus (LGN). The present study was undertaken to determine whether abnormalities in cell number and volume of the LGN are associated with schizophrenia and whether the structural alterations are restricted to either the magnocellular or parvocellular subdivisions of the LGN. Series of Nissl-stained sections spanning the LGN were obtained from 15 schizophrenic and 15 normal control subjects. The optical disector/fractionator sampling method was used to estimate total neuronal number, total glial number and volume of the magnocellular and parvocellular subdivisions of the LGN. Cell number and volume of the LGN in schizophrenic subjects were not abnormal. Volume of both parvocellular and magnocellular layers of the LGN decreased with age. These findings do not support the hypothesis that early visual processing deficits in schizophrenic subjects are due to reduction of neuronal number in the LGN.     

Galanin immunoreactivity within the primate basal forebrain: Evolutionary change between monkeys and apes

Galanin immunoreactivity (GAL-ir) is differentially expressed within the basal forebrain of monkeys and humans. Most monkey magnocellular basal forebrain neurons colocalize GAL-ir. In contrast, virtually no human magnocellular basal forebrain neurons express GAL-ir. Rather, an extrinsic galaninergic fiber plexus innervates these neurons in humans. The present study examined the expression of GAL-ir within the basal forebrain of apes to establish the phylogenetic level at which this transformation occurs. The staining patterns of GAL-ir within the basal forebrain of both lesser (gibbons) and great (chimpanzee and gorilla) apes were compared to that previously observed within monkeys and humans. All apes displayed a pattern of basal forebrain GAL-ir indistinguishable from humans. GAL-ir was not expressed within ape basal forebrain magnocellular neurons as seen in monkeys. Rather like humans, a dense collection of GAL-ir fibers was seen in close apposition to magnocellular perikarya. In addition, a few GAL-ir parvicellular neurons were scattered within the ape basal forebrain. These data indicate that the evolutionary change in the expression of GAL-ir within the primate basal forebrain occurs at the branch point of monkeys and apes. © 1993 Wiley-Liss, Inc.     

Dysfunction of early-stage visual processing in schizophrenia.

OBJECTIVE: Schizophrenia is associated with deficits in higher-order processing of visual information. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. METHOD: Steady-state visual-evoked potential responses were recorded over the occipital cortex in patients with schizophrenia and in age- and sex-matched comparison volunteers. Visual-evoked potentials were obtained for stimuli composed of isolated squares that were modulated sinusoidally in luminance contrast, number of squares, or chromatic contrast in order to emphasize magnocellular or parvocellular visual pathway activity. RESULTS: Responses of patients to magnocellular-biased stimuli were significantly lower than those of comparison volunteers. These lower response levels were observed in conditions using both low luminance contrast and large squares that biased processing toward the magnocellular pathway. In contrast, responses to stimuli that biased processing toward the parvocellular pathway were not significantly different between schizophrenia patients and comparison volunteers. A significant interaction of group and stimulus type was observed in the condition using low luminance contrast. CONCLUSIONS: These findings suggest a dysfunction of lower-level visual pathways, which was more prominent for magnocellular than parvocellular biased stimuli. The magnocellular pathway helps in orienting toward salient stimuli. A magnocellular pathway deficit could contribute to higher-level visual cognitive deficits in schizophrenia.     

Two distinct visual pathways through the superficial pretectum in a percomorph teleost

The connections of the superficial pretectum and of nucleus isthmi were examined in a percomorph teleost, Lepomis cyanellus. Horseradish peroxidase was injected either with a pin into the parvicellular nucleus of the superficial pretectum or pressure injected into nucleus isthmi; the isthmal injections retrogradely labelled the neurons of the magnocellular nucleus of the superficial pretectum. Two main visual pathways can be recognized: The first projects from the retina to the parvicellular nucleus, and then to the intermediate nucleus of the superficial pretectum, the inferior raphe nucleus, and the trochlear nucleus. The second projects from the retina via the optic tectum to the magnocellular nucleus of the superficial pretectum, and from there to nucleus isthmi and the lateral thalamic nucleus; nucleus isthmi and the lateral thalamic nucleus project back to the optic tectum, and nucleus isthmi also projects back to the magnocellular nucleus. The two pathways are interconnected to some extent because both nucleus isthmi and the optic tectum project to the parvicellular nucleus; nevertheless, we suggest that they may be functionally and evolutionarily distinct. Compared to percomorphs, the first pathway appears reduced in cyprinid teleosts such as goldfish. Furthermore, the magnocellular nucleus of the second pathway is completely different in cyprinids, both in cellular architecture and in efferent connections. A phylogenetic analysis suggests that cyprinid ancestors went through a period of reduced vision and that the magnocellular nucleus of the superficial pretectum in modern cyprinids has been either extensively modified from the primitive condition or lost entirely and replaced by a superficially similar structure.