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PubMed1997

Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia.

BACKGROUND: The identification of novel subtypes of the dopamine receptors has renewed interest in the involvement of dopaminergic mechanisms in schizophrenia. We determined the expression of transcripts encoding the dopamine receptors in the brains of schizophrenic patients. METHODS: The levels of the messenger RNA molecules encoding the 5 dopamine receptors were quantified in postmortem brain samples from 16 schizophrenic patients and 9 control subjects. Samples from multiple regions of the prefrontal cortex, primary visual cortex, and striatum were subjected to in situ hybridization followed by quantitative image analysis. RESULTS: Expression of dopamine receptor transcripts did not differ between schizophrenic patients and controls in striatum or visual cortex. Dramatic decreases of dopamine receptor transcripts were found in the prefrontal cortex, but these changes were restricted to the D3 and D4 receptors, and localized to Brodmann area 11 (orbitofrontal cortex). CONCLUSIONS: Cortical dopaminergic neurotransmission may be disrupted in schizophrenia at the level of receptor expression. There appears to be a focal abnormality of D3 and D4 messenger RNA expression in the prefrontal cortex, with down-regulation of both, consistent with prefrontal cortical hypodopaminergia in schizophrenia.

Aged↗
PubMed2004

Cyto- and chemoarchitecture of the cerebral cortex of the Australian echidna (Tachyglossus aculeatus). I. Areal organization.

We have examined the topography of the cerebral cortex of the Australian echidna (Tachyglossus aculeatus), using Nissl and myelin staining, immunoreactivity for parvalbumin, calbindin, and nonphosphorylated neurofilament protein (SMI-32 antibody), and histochemistry for acetylcholinesterase (AChE) and NADPH diaphorase. Myelinated fibers terminating in layer IV of the cortex were abundant in the primary sensory cortical areas (areas S1, R, and PV of somatosensory cortex; primary visual cortex) as well as the frontal cortex. Parvalbumin immunoreactivity was particularly intense in the neuropil and somata of somatosensory regions (S1, R, and PV areas) but was poor in motor cortex. Immunoreactivity with the SMI-32 antibody was largely confined to a single sublayer of layer V pyramidal neurons in discrete subregions of the somatosensory, visual, and auditory cortices, as well as a large field in the frontal cortex (Fr1). Surprisingly, SMI-32 neurons were absent from the motor cortex. In AChE preparations, S1, R, V1, and A regions displayed intense reactivity in supragranular layers. Our findings indicate that there is substantial regional differentiation in the expanded frontal cortex of this monotreme. Although we agree with many of the boundaries identified by previous authors in this unusual mammal (Abbie [1940] J. Comp. Neurol. 72:429-467), we present an updated nomenclature for cortical areas that more accurately reflects findings from functional and chemoarchitectural studies.

Acetylcholinesterase↗
PubMed2001

Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI.

Processing the human face is at the focal point of most social interactions, yet this simple perceptual task is difficult for individuals with autism, a population that spends limited amounts of time engaged in face-to-face eye contact or social interactions in general. Thus, the study of face processing in autism is not only important because it may be integral to understanding the social deficits of this disorder, but also, because it provides a unique opportunity to study experiential factors related to the functional specialization of normal face processing. In short, autism may be one of the only disorders where affected individuals spend reduced amounts of time engaged in face processing from birth. Using functional MRI, haemodynamic responses during a face perception task were compared between adults with autism and normal control subjects. Four regions of interest (ROIs), the fusiform gyrus (FG), inferior temporal gyrus, middle temporal gyrus and amygdala were manually traced on non-spatially normalized images and the percentage ROI active was calculated for each subject. Analyses in Talairach space were also performed. Overall results revealed either abnormally weak or no activation in FG in autistic patients, as well as significantly reduced activation in the inferior occipital gyrus, superior temporal sulcus and amygdala. Anatomical abnormalities, in contrast, were present only in the amygdala in autistic patients, whose mean volume was significantly reduced as compared with normals. Reaction time and accuracy measures were not different between groups. Thus, while autistic subjects could perform the face perception task, none of the regions supporting face processing in normals were found to be significantly active in the autistic subjects. Instead, in every autistic patient, faces maximally activated aberrant and individual-specific neural sites (e.g. frontal cortex, primary visual cortex, etc.), which was in contrast to the 100% consistency of maximal activation within the traditional fusiform face area (FFA) for every normal subject. It appears that, as compared with normal individuals, autistic individuals 'see' faces utilizing different neural systems, with each patient doing so via a unique neural circuitry. Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA.

Adult↗
PubMed2006

Neural correlates of sustained spatial attention in human early visual cortex.

Attention is thought to enhance perceptual performance at attended locations through top-down attention signals that modulate activity in visual cortex. Here, we show that activity in early visual cortex is sustained during maintenance of attention in the absence of visual stimulation. We used functional magnetic resonance imaging (fMRI) to measure activity in visual cortex while human subjects performed a visual detection task in which a variable-duration delay period preceded target presentation. Portions of cortical areas V1, V2, and V3 representing the attended part of the visual field exhibited sustained increases in activity throughout the delay period. Portions of these cortical areas representing peripheral, unattended parts of the visual field displayed sustained decreases in activity. The data were well fit by a model that assumed the sustained neural activity was constant in amplitude over a time period equal to that of the actual delay period for each trial. These results demonstrate that sustained attention responses are present in early visual cortex (including primary visual cortex), in the absence of a visual stimulus, and that these responses correlate with the allocation of visuospatial attention in both the spatial and temporal domains.

Attention↗
PubMed2003

Neuronal classes in the isocortex of a monotreme, the Australian echidna (Tachyglossus aculeatus).

We have used Valverde-Golgi and Golgi-Colonnier techniques to analyze cortical neuronal morphology in four regions (frontal cortex, primary motor cortex, primary somatosensory cortex, primary visual cortex) of the isocortex of the echidna (Tachyglossus aculeatus). Eight classes of neurons could be identified--pyramidal, spinous bipolar, aspinous bipolar, spinous bitufted, aspinous bitufted, spinous multipolar, aspinous multipolar and neurogliaform. All except the pyramidal neurons were morphologically similar to neuronal classes seen in eutherian and metatherian isocortex. Pyramidal neurons made up a small proportion of all cortical neurons encountered in our preparations of echidna cortex (34% in visual cortex, 35% in somatosensory cortex, 41% in frontal cortex and 49% in motor cortex) compared to both reported values in eutherian cortex and values we found in rat cortex impregnations prepared in an identical fashion to the echidna material (75% in rat motor and 78% in rat somatosensory cortex). Many pyramidal neurons in the echidna isocortex were atypical (30-42% depending on region) with inverted somata, short or branching apical dendrites and/or few basal dendrites, very different from the usual pyramidal neuron morphology in eutherian cortex. Dendritic spine density on apical and basal dendrites of echidna pyramidal neurons in somatosensory cortex and apical dendrites of motor cortex pyramidal neurons was also lower than that found in the rat. The present findings are consistent with both pyramidal neurons and the many diverse types of non-pyramidal neurons having already emerged as discrete morphological entities very early in mammalian cortical evolution, at the time of divergence of the therian and prototherian lineage.

Animals↗
PubMed2005

Reorganization of visual processing in macular degeneration.

Macular degeneration (MD), the leading cause of visual impairment in the developed world, damages the central retina, often obliterating foveal vision and severely disrupting everyday tasks such as reading, driving, and face recognition. In such cases, the macular damage eliminates the normal retinal input to a large region of visual cortex, comprising tens of square centimeters of surface area in each hemisphere, which is normally responsive only to foveal stimuli. Using functional magnetic resonance imaging, we asked whether this deprived cortex simply becomes inactive in subjects with MD, or whether it takes on new functional properties. In two adult MD subjects with extensive bilateral central retinal lesions, we found that parts of visual cortex (including primary visual cortex) that normally respond only to central visual stimuli are strongly activated by peripheral stimuli. Such activation was not observed (1) with visual stimuli presented to the position of the former fovea and (2) in control subjects with visual stimuli presented to corresponding parts of peripheral retina. These results demonstrate large-scale reorganization of visual processing in MD and will likely prove important in any effort to develop new strategies for rehabilitation of MD subjects.

Fovea Centralis↗
PubMed1999

Organization of intracortical circuits in relation to direction preference maps in ferret visual cortex.

Neurons in the primary visual cortex are selective for the direction of movement of a visual stimulus. Like other stimulus features, direction preference is mapped on the cortical surface in a systematic manner. Intracortical synaptic circuits, in particular inhibitory connections, have been implicated in the emergence of direction selectivity. Whether intracortical inhibition specifically suppresses responses to the nonpreferred direction or has a nonspecific "thresholding" effect is still controversial. To address these questions we investigated the relationship between patterns of intracortical synaptic connections and direction domains in ferret primary visual cortex (area 17) using a combined in vivo-in vitro approach. Excitatory synaptic inputs were iso-direction-tuned. The majority of local inhibitory inputs were also iso-direction-tuned. However, approximately 40% of inhibitory connections originated in regions preferring the opposite direction. These findings indicate that specific inhibitory interactions between cortical regions of opposite direction preference may contribute to the emergence and sharpening of direction selectivity.

Animals↗
PubMed1991

Relation of cortical cell orientation selectivity to alignment of receptive fields of the geniculocortical afferents that arborize within a single orientation column in ferret visual cortex.

Neurons in the primary visual cortex of higher mammals are arranged in columns, and the neurons in each column respond best to light-dark borders of particular orientations. The basis of cortical cell orientation selectivity is not known. One possible mechanism would be for cortical cells to receive input from several lateral geniculate nucleus (LGN) neurons with receptive fields that are aligned in the visual field (Hubel and Wiesel, 1962). We have investigated the relationship between the arrangement of the receptive fields of geniculocortical afferents and the orientation preferences of cortical cells in the orientation columns to which the afferents provide visual input. Radial microelectrode penetrations were made into primary visual cortex of anesthetized adult sable ferrets. Cortical cells were recorded throughout the depth of the cortex, and their orientation preferences were determined. Cortical cell responses were then eliminated by superfusion of the cortex with either kainic acid (Zahs and Stryker, 1988) or muscimol. After the drug treatment, responses from many single units with distinct receptive fields were recorded. These responses were presumed to be those of geniculocortical afferents, because they had the response properties characteristic of LGN neurons, and because they could be recorded only in cortical layers that receive geniculate input. In 16 of 18 cases, the afferent receptive fields recorded in a single penetration covered an elongated region of visual space. In these penetrations, the best-fit line through the centers of the afferent receptive fields generally paralleled the preferred orientation of cortical cells recorded at the same site in cortex. These results are consistent with the Hubel and Wiesel (1962) model for the construction of oriented visual cortical receptive fields from geniculate inputs with aligned receptive fields.

Afferent Pathways↗
PubMed1994

Differential localization of two glutamic acid decarboxylases (GAD65 and GAD67) in adult monkey visual cortex.

Adult monkey primary visual cortex contains a diverse population of stellate neurons that utilize the neurotransmitter gamma aminobutyric acid (GABA). Two glutamic acid decarboxylase (GAD) enzymes that synthesize GABA, GAD65 and GAD67, were localized within these stellate neurons by in situ hybridization of 35S or digoxigenin (DIG) labeled riboprobes. Double labels were done by using 35S GAD67 riboprobe and GABA immunocytochemistry on the same section to verify that the neuronal population identified by immunocytochemistry was the same one studied in the in situ hybridization experiments. We find that GAD65 mRNA and GAD67 mRNA are widely distributed in the cortex, with four bands of heavily labeled neurons in upper layer 2, lower 3, 4C, and 6. GAD67 labeled neurons were more obvious in layer 4C beta, while GAD65 containing neurons were common in layer 1 and white matter. Northern blots and in situ hybridization on sections with both 35S and DIG riboprobes indicate that cortical neurons typically contain more GAD67 mRNA. Cell counts show that 18% of all cortical neurons contain GAD67 mRNA and 13% contain GAD65 mRNA, suggesting that a small population of GABA neurons might lack GAD65. Cell bodies that contain high amounts of GAD65 mRNA are prominent in layers deep 3, 4B, 4C alpha, and 6 and often are the largest cells in their respective layers. Double labels demonstrate that 96% of all GABA+ neurons contain GAD67 mRNA. Neurons heavily labeled for GABA tend to have smaller cell bodies and contain less GAD67 mRNA, while lightly labeled GABA neurons are larger and contain more GAD67 mRNA. These data indicate that most GABA neurons in monkey striate cortex contain both GAD enzymes. Although the differences in GABA content, cell size, laminar distribution, and GAD mRNA concentration suggest different requirements for GAD67 and GAD65 in cortical circuits, our experiments do not reveal what different roles these two enzymes subserve within GABAergic stellate neurons.

Animals↗
PubMed2003

Limit of spared pattern vision following lesions of the immature visual cortex.

Lesions of primary visual cortex sustained early in life spare certain aspects of visual processing that can be linked to expansions of bypass pathways to extrastriate cortex. They also trigger, in an age-dependent way, partial or complete transneuronal retrograde degeneration of beta (X) retinal ganglion cells, which are implicated in visual processing under conditions of low contrast. We used two-dimensional geometric patterns whose saliency was reduced by gradually increasing levels of superimposed masking lines, and by reductions in spatial contrast. Normative data were collected from intact cats, and baseline lesion data were collected from cats with lesions sustained as young adults (postnatal day 180, P180). Experimental data were collected from cats that sustained lesions on P1-3 or P26-30. For high contrast patterns, the adult group was impaired at both acquisition (sequential progressive levels of masking) and concurrent (parallel high and low levels of masking) performance, whereas the early-lesioned groups were impaired only at concurrent performance. All lesion groups were equally impaired when contrast was reduced to modest or lower levels. These results show that sparing of masked-pattern learning is limited to the high end of the spatial contrast domain.

Animals↗
PubMed2002

Suppression without inhibition in visual cortex.

Neurons in primary visual cortex (V1) are thought to receive inhibition from other V1 neurons selective for a variety of orientations. Evidence for this inhibition is commonly found in cross-orientation suppression: responses of a V1 neuron to optimally oriented bars are suppressed by superimposed mask bars of different orientation. We show, however, that suppression is unlikely to result from intracortical inhibition. First, suppression can be obtained with masks drifting too rapidly to elicit much of a response in cortex. Second, suppression is immune to hyperpolarization (through visual adaptation) of cortical neurons responding to the mask. Signals mediating suppression might originate in thalamus, rather than in cortex. Thalamic neurons exhibit some suppression; additional suppression might arise from depression at thalamocortical synapses. The mechanisms of suppression are subcortical and possibly include the very first synapse into cortex.

Action Potentials↗
PubMed2002

The role of feedback in shaping neural representations in cat visual cortex.

In the primary visual cortex, neurons with similar response preferences are grouped into domains forming continuous maps of stimulus orientation and direction of movement. These properties are widely believed to result from the combination of ascending and lateral interactions in the visual system. We have tested this view by examining the influence of deactivating feedback signals descending from the visuoparietal cortex on the emergence of these response properties and representations in cat area 18. We thermally deactivated the dominant motion-processing region of the visuoparietal cortex and used optical and electrophysiological methods to assay neural activity evoked in area 18 by stimulation with moving gratings and fields of coherently moving randomly distributed dots. Feedback deactivation decreased signal strength in both orientation and direction maps and virtually abolished the global layout of direction maps, whereas the basic structure of the orientation maps was preserved. These findings could be accounted for by a selective silencing of highly direction-selective neurons and by the redirection of preferences of less selective neurons. Our data suggest that signals fed back from the visuoparietal cortex strongly contribute to the emergence of direction selectivity in early visual areas. Thus we propose that higher cortical areas have significant influence over fundamental neuronal properties as they emerge in lower areas.

Animals↗
PubMed1982

Thalamic inputs to cytochrome oxidase-rich regions in monkey visual cortex.

In primate primary visual cortex, staining for cytochrome oxidase reveals a regular array of blob-like structures, most prominent in layers II and III but also present in layers V and VI. In an attempt to learn more about the input to these blobs, we injected the lateral geniculate bodies of macaques and squirrel monkeys with [3H]proline or horseradish peroxidase and looked in the cortex for transported label. As expected, label was present in layers IVa, IVc alpha, IVc beta, and VI. In addition, both methods revealed an array of puffs deep in layer III. Seen in tangential sections, the puffs precisely matched the cytochrome blobs. These results indicate a projection from the lateral geniculate body to the blob regions deep in layer II/III, either indirect via layer IV or more likely direct. In area 18 stained for cytochrome oxidase, we also observed complex banding patterns; these were remarkably similar to the pattern found after [3H]proline or horseradish peroxidase injection and were also similar to the pattern produced with 2-deoxyglucose labeling after stimulation with vertical or horizontal stripes; the proline and peroxidase labels probably represent a projection from the pulvinar to area 18.

Animals↗
PubMed2000

Arrangement of orientation pinwheel centers around area 17/18 transition zone in cat visual cortex.

In the primary visual cortex of higher mammals, orientation preferences are represented continuously except for singular points, so-called pinwheel centers. In spite of the uniqueness of orientation pinwheel centers, very little is known about the pattern of their arrangement. In this study we examined the arrangement of orientation pinwheel centers in the cat visual cortex by optical imaging of intrinsic signals. Our results demonstrate that orientation pinwheel centers are arranged in a unique geometric pattern around the area 17/18 transition zone: pinwheel centers of the same type are arranged in rows parallel to the transition zone, and rows of clockwise and counterclockwise pinwheel centers are arranged alternately. We suggest that the areal border imposes a strong restriction on the pattern formation of orientation preference maps in the visual cortex.

Animals↗
PubMed1997

Ocular dominance peaks at pinwheel center singularities of the orientation map in cat visual cortex.

In the primary visual cortex of monkey and cat, ocular dominance and orientation are represented continuously and simultaneously, so that most neighboring neurons respond optimally to visual stimulation of the same eye and orientation. Maps of stimulus orientation are punctuated by singularities referred to as "pinwheel centers," around which all orientations are represented. Given that the orientation map is mostly continuous, orientation singularities are a mathematical necessity unless the map consists of perfectly parallel rows, and there is no evidence that the singularities play a role in normal function or development. We report here that in cats there is a strong tendency for peaks of ocular dominance to lie on the pinwheel center singularities of the orientation map. This relationship predicts but is not predicted by the tendencies, previously reported, for pinwheels to lie near the center lines of ocular dominance bands and for iso-orientation bands to cross ocular dominance boundaries at right angles. The coincidence of ocular dominance peaks with orientation singularities is likely to reflect a strong underlying functional link between the two visual cortical maps.

Animals↗
PubMed2004

Geometrical computations explain projection patterns of long-range horizontal connections in visual cortex.

Neurons in primary visual cortex respond selectively to oriented stimuli such as edges and lines. The long-range horizontal connections between them are thought to facilitate contour integration. While many physiological and psychophysical findings suggest that collinear or association field models of good continuation dictate particular projection patterns of horizontal connections to guide this integration process, significant evidence of interactions inconsistent with these hypotheses is accumulating. We first show that natural random variations around the collinear and association field models cannot account for these inconsistencies, a fact that motivates the search for more principled explanations. We then develop a model of long-range projection fields that formalizes good continuation based on differential geometry. The analysis implicates curvature(s) in a fundamental way, and the resulting model explains both consistent data and apparent outliers. It quantitatively predicts the (typically ignored) spread in projection distribution, its nonmonotonic variance, and the differences found among individual neurons. Surprisingly, and for the first time, this model also indicates that texture (and shading) continuation can serve as alternative and complementary functional explanations to contour integration. Because current anatomical data support both (curve and texture) integration models equally and because both are important computationally, new testable predictions are derived to allow their differentiation and identification.

Animals↗
PubMed2002

Visual cortex excitability increases during visual mental imagery--a TMS study in healthy human subjects.

Previous neuroimaging studies provided evidence that visual mental imagery relies, in part, on the primary visual cortex. We hypothesized that, analogous to the finding that motor imagery increases the excitability of motor cortex, visual imagery should increase visual cortex excitability, as indexed by a decrease in the phosphene threshold (PT). In order to test visual cortex excitability, the primary visual cortex was stimulated with transcranial magnetic stimulation (TMS), so as to elicit phosphenes in the right lower visual quadrant. Subjects performed a visual imagery task and an auditory control task. We applied TMS with increasing intensity to determine the PT for each subject. Independent of the quadrant in which subjects placed their visual images, imagery decreased PT compared to baseline PT; in contrast, the auditory task did not change PT. These findings demonstrate for the first time a short-term, task-dependent modulation of PT. These results constitute evidence that early visual areas participate in visual imagery processing.

Adult↗
PubMed1998

Visual zone of the claustrum shows localizational and organizational differences among rat, guinea pig, rabbit and cat.

The retrograde axonal transport method was used to compare the topography and organization of the visual zone of the claustrum in rat, guinea pig, rabbit and cat. First, massive Fluoro-Gold injections were placed into the primary visual cortex and the secondary areas. Experiments showed differences in the location of the visual zone among the animals under study. In rat, the visual zone occupied the posteroventral part of the claustrum and spread to its anterior pole. In guinea pig, neurons projecting to the visual cortex were located dorsally in the posterior half of the claustrum. In rabbit, similarly to the rat, they were localized in the posteroventral part; however, they did not reach the anterior pole. In cat, neurons that project to the visual cortex were concentrated dorsally in the posterior fourth of the claustrum. In double-injection experiments, Fast Blue and Diamidino Yellow were placed into the primary and secondary visual areas in various combinations. The experiments showed that in the rat and the rabbit claustral neurons project to primary visual cortex (area 17) as well as to both secondary visual areas (areas 18a and b). Populations of neurons sending axons to the primary and secondary areas showed full overlap. The presence of double-labeled neurons indicates that some claustral neurons project both to the primary and secondary fields. In cat, neurons that project to the primary visual cortex appear to be clearly separated from those connected with the secondary visual area, as no double-labeled neurons were found. In all studied species, the double injections placed into the visual and primary somatosensory cortex did not result in any double-labeling neurons. Our results indicate that the location of the visual zone in the posterior part of the claustrum is a phylogenetically stable feature, whereas its dorsoventral shift as well as the extent toward the anterior pole is related to the particular species. The overlap of neurons projecting to the primary and secondary visual areas in the rat and rabbit as well as the separation of both projections in cat appear to reflect the higher degree of complexity of the visual system in the latter.

Animals↗