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PubMed2026

Alternative splicing in layer 3 pyramidal neurons differs across regions of the human cortical hierarchy.

The primate neocortex is organized as hierarchical networks of functionally distinct regions. In the dorsal visual stream network, information is conveyed from primary visual (V1) to posterior parietal (PPC) and dorsolateral prefrontal (DLPFC) cortices. This information transfer is mediated primarily by layer 3 pyramidal neurons (L3PNs), which differ across these regions in morphology, excitability, and intracellular Ca2+ regulation. These region-specific L3PN properties may be influenced by alternative splicing (AS) of pre-mRNA, which occurs extensively in the human brain. To explore the potential impact of AS of region-specific L3PN properties, we analyzed RNA-seq data from pools of L3PNs dissected from human V1, PPC, and DLPFC. We found that <6% of genes with regional differences in expression also differed in AS. This finding indicates that the absence of transcriptional differences is insufficient to conclude that a gene does not contribute functional differences between regions. Additionally, there were numerous regional differences in AS, particularly between V1 and DLPFC or PPC L3PNs, which involved genes associated with neuron morphology and Ca2+ regulation; > 90% of these AS differences involved functionally relevant sequences (eg phosphorylation sites, etc.). These findings suggest AS contributes to region-specific L3PN properties relevant to the function of the dorsal visual stream.

Humans↗

PubMedDate not supplied

Possible origin of glutamatergic projections to the midbrain periaqueductal gray and deep layer of the superior colliculus of the rat.

The possible origin of glutamatergic input to the rodent periaqueductal gray (PAG) was analyzed utilizing a combined retrograde transport-immunocytochemical technique. Injections of wheat germ agglutinin-horseradish peroxidase were made into the PAG of 12 adult rats and into the deep layer of the superior colliculus in 2 rats. The brain tissue was first reacted histochemically to demonstrate the retrograde tracer and subsequently processed with immunohistochemical techniques using a recently developed monoclonal glutamate antibody. Following PAG injections, several brain areas were found to contain double-labeled neurons. The greatest number of double-labeled glutamate-like immunoreactive neurons were observed in the zona incerta, spinal trigeminal nucleus, cuneiform nucleus, cingulate cortex, cerebellar interpositus nucleus, deep mesencephalic nucleus and the PAG itself. Double-labeled neurons were also observed in several other nuclei including the pretectal nuclei, the frontal and occipital cortex, several reticular nuclei, the dorsomedial hypothalamic nucleus, and the substantia nigra. Many of the same nuclei contained double-labeled neurons following collicular injections, but in addition, double-stained cells were found in the primary visual cortex, lateral dorsal and lateral posterior thalamic nuclei, nucleus of the posterior commissure, ventral lateral geniculate nucleus, dorsal column nuclei and several additional pretectal nuclei. The results of this double-labeling study raise the possibility that these nuclei may provide glutamatergic inputs to the midbrain PAG and/or superior colliculus. These putative glutamatergic afferent projections may ultimately influence the PAG's role in several important functions including antinociception, defensive mechanisms or vocalization and may also play a role in the superior collicular involvement in defensive mechanisms, in visuo-motor integration in the orienting reflex and in facilitating shifts in gaze.

Animals↗

PubMedDate not supplied

Degradation of response modulation of visual cortical cells in cats with chronic exposure to morphine.

The primary visual cortex (V1) plays an important role in vision and visual perception. Studies in many brain regions demonstrate that opiate abuse can change excitatory and inhibitory neurotransmission. To investigate the effect of chronic morphine exposure on the response modulation of V1 simple and complex neurons, we carried out in vivo extracellular recordings in V1 of morphine- and saline-treated (control) cats. Response modulation was quantified as the ratio of first Fourier components (F1) to the mean response (F0). Compared with saline-treated cats, V1 neurons in morphine-treated cats exhibited weaker response modulation and a longer time course of response. The decrease of response modulation was caused by an increase of F0. Further, morphine re-exposure significantly improved the response properties of V1 neurons in morphine-treated cats. These results suggest that chronic morphine treatment leads to a significant degradation of response modulation of V1 neurons and a morphine dependence of primary visual cortical function.

Action Potentials↗

PubMed2003

Independent projection streams from macaque striate cortex to the second visual area and middle temporal area.

The interareal wiring of the neocortex is usually depicted as a network of single point-to-point connections, often side-stepping the possibility that some neurons may project to multiple cortical areas. The prevalence of such neurons is unknown; if they are abundant, cortical circuits are more likely to be connectionally diffuse. We used a dual-tracer approach to determine whether single neurons in the macaque primary visual cortex (V1) project to two extrastriate areas, the second visual area (V2) and the middle temporal area (MT). We found two large intermingled groups of single-labeled neurons in layer 4B of V1 projecting independently to either V2 or MT. A third, sparser group of double-labeled neurons projected to both areas; we termed these manifold neurons. We also found that MT-projecting cells were distributed indiscriminately with respect to cytochrome oxidase compartment in layer 4B, revealing a subpopulation that provides a potential source of patch input from V1 to MT. The results demonstrate that primary sensory cortices can use multiple projection strategies to distribute signals to higher areas, and suggest that feedforward projections may route signals with more specificity than feedback pathways.

Animals↗

PubMed1981

Projections from the superior colliculus and the neocortex to the pulvinar nucleus in Galago.

We have studied the projections from the superior colliculus and the neocortex to the pulvinar nucleus in Galago senegalensis by using the retrograde transport of horseradish peroxidase (HRP). Injections of various parts of the pulvinar complex, both the inferior and superior divisions, both the tectorecipient zone and the nontectorecipient zone as defined by Glendenning et. al. ('75), produce labeled cells in the lower tier of stratum griseum superficiale. The distribution of labeled cells in the superior colliculus varies with the locus of the injection, indicating a retinotopic projection system from the entire superior colliculus to all sectors of the pulvinar complex. These experiments also provide an opportunity to study the distribution and laminar origin of neurons giving rise to cortical descending projections. The entire visual cortex projects onto the pulvinar complex. The cells or origin can be divided into two populations--one located in layer V and the other in layer VI. In seven of the nine cases reported, the layer V population is restricted entirely or mainly to the striate area. In the two exceptional cases, the layer V population is located in the adjacent extrastriate cortex, areas 18 and 19. The difference in the layer of origin of the cortical descending fibers reflects a difference in the layer of termination of the reciprocal ascending projection. These findings identify the entire visual field as primary visual cortex. The importance of this conclusion is underscored by the fact that the visual field comprises as much as one-half of the whole neocortex.

Animals↗

PubMedDate not supplied

Cytochrome-oxidase blobs and intrinsic horizontal connections of layer 2/3 pyramidal neurons in primate V1.

Pyramidal neurons in superficial layers of cerebral cortex have extensive horizontal axons that provide a substrate for lateral interactions across cortical columns. These connections are believed to link functionally similar regions, as suggested by the observation that cytochrome-oxidase blobs in the monkey primary visual cortex (V1) are preferentially connected to blobs and interblobs to interblobs. To better understand the precise relationship between horizontal connections and blobs, we intracellularly labeled 20 layer 2/3 pyramidal neurons in tangential living brain slices from V1 of macaque monkeys. The locations of each cell body and the cell's synaptic boutons relative to blobs were quantitatively analyzed. We found evidence for two cell types located at characteristic distances from blob centers: (1) neurons lacking long-distance, clustered axons (somata 130-200 microm from blob centers) and (2) cells with clustered, long-distance axon collaterals (somata < 130 microm or >200 microm from blob centers). For all cells, synaptic boutons close to the cell body were located at similar distances from blob centers as the cell body. The majority of boutons from cells lacking distal axon clusters were close to their cell bodies. Cells located more than 200 microm from blob centers were in interblobs and had long-distance clustered axon collaterals selectively targeting distant interblob regions. Cells located less than 130 microm from blob centers were found within both blobs and interblobs, but many were close to traditionally defined borders. The distant synaptic boutons from these cells were generally located relatively near to blob centers, but the neurons closest to blob centers had synaptic boutons closer to blob centers than those farther away. There was not a sharp transition that would suggest specificity for blobs and interblobs as discrete, binary entities. Instead they appear to be extremes along a continuum. These observations have important implications for the function of lateral interactions within V1.

Animals↗

PubMed1982

Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method.

The [18F]fluorodeoxyglucose (FDG) scan method with positron emission computed tomography was used to determine patterns of local cerebral glucose utilization (LCMRglu) in 40 normal volunteer subjects aged 18 to 78 years. Throughout all the studies, each subject was quiet, without movement, with eyes open and ears unplugged, exposed only to ambient room light and sound. For the entire group, whole brain mean CMRglu was 26.1 +/- 6.1 mumol 100 g-1 min-1 (mean +/- SD, n = 40). At age 78, mean CMRglu was, on the average, 26% less than at age 18, an alteration of the same order as the variance among subjects at any age. The gradual decline of mean CMRglu with advancing age occurred at a faster rate than was reported for mean cerebral oxygen utilization, possibly due to increasingly altered pathways for glucose utilization, or to increasing oxidation of ketone bodies or other alternative substrates. Glucose utilization in the hemispheres was symmetrical and mean CMRglu of overall cortex, caudate, and thalamus was equal in individuals at all ages. The slopes of decline with age were similar when LCMRglu was averaged over zones corresponding to centrum semiovale, caudate, putamen, and frontal, temporal, parietal, occipital, and primary visual cortex. However, the metabolic ratio of superior frontal cortex to superior parietal cortex declined with age, possibly due to selective degeneration of superior frontal cortex or to differences between age groups in the sensory and cognitive response to the study. These results should be useful in distinguishing age from disease effects when the FDG scan method is used.

Adolescent↗

PubMed1993

Monocular deprivation effects in the rat visual cortex and lateral geniculate nucleus are prevented by nerve growth factor (NGF). II. Lateral geniculate nucleus.

In the preceding paper (Berardi et al. Proc. R. Soc. Lond. B 251, 17 (1993)), it has been shown that nerve growth factor (NGF) prevents the functional and anatomical alterations induced by monocular deprivation (MD) at the level of the visual cortex. Here we report that an exogenous supply of NGF prevents the shrinkage of neurons in the deprived laminae of lateral geniculate nucleus (LGN). The soma size distribution for the deprived ipsilateral laminae of MD rats is shifted towards smaller sizes (mean percentage of shrinkage with respect to the ipsilateral undeprived lamina = 21%, s.d. = 2%). As in other mammals, MD affects LGN relay neurons and spares LGN neurons projecting to the monocular portion of primary visual cortex. In NGF-treated animals we found that the soma size distributions for the deprived and undeprived ipsilateral laminae extensively overlap. The results of the two papers show that an exogenous supply of NGF prevents MD effects at both levels, visual cortex and LGN, and suggest a role for NGF in the plasticity of the geniculo-cortical pathway.

Animals↗

PubMed2001

Consistency of encoding in monkey visual cortex.

Are different kinds of stimuli (for example, different classes of geometric images or naturalistic images) encoded differently by visual cortex, or are the principles of encoding the same for all stimuli? We examine two response properties: (1) the range of spike counts that can be elicited from a neuron in epochs representative of short periods of fixation (up to 400 msec), and (2) the relation between mean and variance of spike counts elicited by different stimuli, that together characterize the information processing capabilities of a neuron using the spike count code. In monkey primary visual cortex (V1) complex cells, we examine responses elicited by static stimuli of four kinds (photographic images, bars, gratings, and Walsh patterns); in area TE of inferior temporal cortex, we examine responses elicited by static stimuli in the sample, nonmatch, and match phases of a delayed match-to-sample task. In each area, the ranges of mean spike counts and the relation between mean and variance of spike counts elicited are sufficiently similar across experimental conditions that information transmission is unaffected by the differences across stimulus set or behavioral conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically significant but small differences, the median difference in transmitted information for these neurons was 0.9%]. Encoding therefore appears to be consistent across experimental conditions for neurons in both V1 and TE, and downstream neurons could decode all incoming signals using a single set of rules.

Action Potentials↗

PubMed2002

Study of the visual evoked magnetic field with the m-sequence technique.

PURPOSE: Multifocally stimulated visual evoked magnetic field (VEF) examination with an m-sequence technique (multifocal VEF; mVEF) was studied, and the neural generators at peaks of mVEF were estimated in the visual cortex. METHODS: Visual field stimulation was generated by a multifocal testing system with use of the m-sequence technique. The stimulation pattern covered a central area extending from 0.6 degrees to 10 degrees in radius outward from the center of four visual-field quadrants. The stimulation pattern was projected onto a screen by a liquid crystal projector. VEFs of 14 healthy adults were recorded with a 160-channel, whole-head-type magnetoencephalography (MEG) system. The output signals of 16 selected MEG sensors covering the occipital region were recorded for each subject with the multifocal testing system, and the second-order responses were calculated. The analyzed response data files were transferred to the MEG system, a single equivalent current dipole (ECD) was estimated to locate the neural generator, and the localization was superimposed onto the corresponding brain magnetic resonance image of the subject. RESULTS: mVEFs showed three peak waves (N75m, P100m, N145m) in 75% of the subjects and two peak waves (N75m, N145m) in 25%. (N, P and m denote negative, positive, and magnetic fields, respectively.) Latencies of the first and the last peak were similar between the two kinds of peak waves. ECD examination showed more than 97% of goodness of fit at all peaks, and the relation between EDCs and the stimulated visual field coincided with a retinotopic organization that fit a cruciform model in all subjects. ECD depths from the occipital pole were similar to the depth expected from the human linear cortical magnification factor model in all subjects. Main neural generators of all mVEF components (N75m, P100m, N145m) were shown in the striate cortex (V1). CONCLUSIONS: Testing the VEF with an m-sequence technique showed stable responses to simultaneous stimulation of four visual-field quadrants. Consistency of correlation of the estimated ECD with the known cortical organization of the primary visual cortex confirmed the reliability of this examination. The three mVEF peaks were thought to derive mainly from V1 activity.

Adult↗

PubMedDate not supplied

Microglia and astrocytes may participate in the shaping of visual callosal projections during postnatal development.

In the adult cat, axons running through the corpus callosum interconnect the border between the visual cortical areas 17 and 18 (A17 and A18) of both hemispheres. This specific pattern emerges during postnatal development, under normal viewing conditions (NR), from the elimination of initially exuberant callosal projections. In contrast, if the postnatal visual experience is monocular from birth (MD), juvenile callosal projections are stabilised throughout A17 and A18. The present study aimed at using such a model in vivo to find indications of a contribution of glial cells in the shaping of projections in the developing CNS through interactions with neurones, both in normal and pathological conditions. As a first stage, the distribution and the morphology of microglial cells and astrocytes were investigated from 2 weeks to adulthood. Microglial cells, stained with isolectin-B4, were clustered in the white matter below A17 and A18. Until one month, these clustered cells displayed an ameboid morphology in NR group, while they were more ramified in MD animals. Their phenotype thus depends on the postnatal visual experience, which indicates that microglial cells may interact with axons of visual neurones. It also suggests that they may differentially contribute to the elimination and the stabilisation of juvenile exuberant callosal fibres in NR and MD animals respectively. Beyond one month, microglial cells were very ramified in both experimental groups. Astrocytes were labelled with a GFAP-antibody. The distributions of connexins 43 (Cx43) and 30 (Cx30), the main proteic components of gap junction channels in astrocytes, were also investigated using specific antibodies. Both in NR and MD groups, until 1 month, GFAP-positive astrocytes and Cx43 were mainly localised within the subcortical white matter. Then GFAP, Cx43 and Cx30 stainings progressively appeared within the cortex, throughout A17 and A18 but with a differential laminar expression according to the age. Thus, the distributions of both astrocytes and connexins changed with age; however, the monocular occlusion had no visible effect. This suggests that astrocytes may contribute to the postnatal development of neuronal projections to the primary visual cortex, including visual callosal projections.

Animals↗

PubMed2001

Estimating receptive field size from fMRI data in human striate and extrastriate visual cortex.

Functional magnetic resonance imaging (fMRI) was used to estimate the average receptive field sizes of neurons in each of several striate and extrastriate visual areas of the human cerebral cortex. The boundaries of the visual areas were determined by retinotopic mapping procedures and were visualized on flattened representations of the occipital cortex. Estimates of receptive field size were derived from the temporal duration of the functional activation at each cortical location as a visual stimulus passed through the receptive fields represented at that location. Receptive fields are smallest in the primary visual cortex (V1). They are larger in V2, larger again in V3/VP and largest of all in areas V3A and V4. In all these areas, receptive fields increase in size with increasing stimulus eccentricity. The results are qualitatively in line with those obtained by others in macaque monkeys using neurophysiological methods.

Adult↗

PubMed1998

Chronic exposure to either somatostatin (SS) or octreotide, a long-lasting SS analogue, affects SS expression in the postnatal visual cortex of the rat.

The peptide somatostatin (SS) is widely distributed in the mammalian brain where it modulates neuronal activity through interactions with specific membrane-bound receptor subtypes (ssts). Five different ssts were characterized so far (sst1-5) and their selective agonists were developed on the basis of their binding specificity. SS and ssts are transiently expressed in the developing brain, suggesting a functional role of somatostatinergic systems in neuronal maturation. In the present study, we investigated the effects of chronic exposure to either the SS synthetic analogue, SS-14 or octreotide (a long-acting sst2-preferring analogue) on the maturation of SS-immunoreactivity (-ir) in the primary visual cortex of the rat. SS-ir maturation was investigated both by an evaluation of the number of SS-immunoreactive cells and by radioimmunoassay (RIA) to measure the levels of SS in the postnatal visual cortex. In the visual cortex of normal rats, the number of SS-positive cells markedly increased during the second postnatal week and then significantly decreased until the adult value was reached at the third week. Early and repeated intracerebroventricular (i.c.v.) injections of either SS-14 or octreotide prevented the increase in the number of SS-positive cells, with adult values reached at the end of the first postnatal week. Similarly, administration of either SS-14 or octreotide significantly decreased the SS content of the visual cortex, measured at the end of the second postnatal week. These results show that high local concentrations of either SS-14 or octreotide interfere with SS expression in developing cortical neurons in a restricted postnatal period.

Aging↗

PubMed2000

Microsaccadic eye movements and firing of single cells in the striate cortex of macaque monkeys.

When viewing a stationary object, we unconsciously make small, involuntary eye movements or 'microsaccades'. If displacements of the retinal image are prevented, the image quickly fades from perception. To understand how microsaccades sustain perception, we studied their relationship to the firing of cells in primary visual cortex (V1). We tracked eye movements and recorded from V1 cells as macaque monkeys fixated. When an optimally oriented line was centered over a cell's receptive field, activity increased after microsaccades. Moreover, microsaccades were better correlated with bursts of spikes than with either single spikes or instantaneous firing rate. These findings may help explain maintenance of perception during normal visual fixation.

Action Potentials↗

PubMed2005

Neuronal mechanisms for illusory brightness perception in humans.

Biological visual systems are extraordinarily capable of recovering the shape and brightness of objects from sparse and fragmentary information. Using functional magnetic imaging, we show that two associative areas of the dorsal pathway--in the caudal region of the intrapariatal sulcus and in the lateral occipital sulcus--respond specifically to the Craik-O'Brien-Cornsweet illusion generated by high-pass filtered edges. Other visual areas, including primary visual cortex, also respond strongly to the retinotopic location of the edge, but these areas respond equally well to a line of matched contrast and detectability, rather than specifically to the brightness illusion. The reconstruction of surface and/or its brightness seems to be achieved by associative areas from the information about visual features provided by the primary visual cortices, even where there is no physical difference in luminance.

Adult↗

PubMedDate not supplied

Fuzzy clustering of gradient-echo functional MRI in the human visual cortex. Part I: reproducibility.

Reproducibility of human functional MRI (fMRI) studies is essential for clinical and neuroresearch applications of this new human brain mapping method. Based on a recently presented study on reproducibility of gradient-echo fMRI in the human visual cortex (Moser et al. Magn Reson Imaging 1996; 14:567-579), comparing the performance of three different threshold strategies for correlation analysis, we demonstrate that (a) fuzzy clustering is a robust, model-independent method to extract functional information in time and space; (b) intertrial reproducibility of cortical activation is significantly improved by the capability of fuzzy clustering to separate signal contributions from larger vessels, running perpendicular to the slice orientation, from activation apparently close to the primary visual cortex; and (c) for repeated single subject studies, SDs of <20% for signal enhancement in approximately 80% of the studies and SDs of <30% for activated area size in approximately 65% of the studies are obtained. This, however, depends also on signal-to-noise ratio, (motion) artifacts, and subject cooperation.

Adult↗

PubMed2005

Predicting the stream of consciousness from activity in human visual cortex.

Can the rapid stream of conscious experience be predicted from brain activity alone? Recently, spatial patterns of activity in visual cortex have been successfully used to predict feature-specific stimulus representations for both visible and invisible stimuli. However, because these studies examined only the prediction of static and unchanging perceptual states during extended periods of stimulation, it remains unclear whether activity in early visual cortex can also predict the rapidly and spontaneously changing stream of consciousness. Here, we used binocular rivalry to induce frequent spontaneous and stochastic changes in conscious experience without any corresponding changes in sensory stimulation, while measuring brain activity with fMRI. Using information that was present in the multivariate pattern of responses to stimulus features, we could accurately predict, and therefore track, participants' conscious experience from the fMRI signal alone while it underwent many spontaneous changes. Prediction in primary visual cortex primarily reflected eye-based signals, whereas prediction in higher areas reflected the color of the percept. Furthermore, accurate prediction during binocular rivalry could be established with signals recorded during stable monocular viewing, showing that prediction generalized across viewing conditions and did not require or rely on motor responses. It is therefore possible to predict the dynamically changing time course of subjective experience with only brain activity.

Adult↗

PubMed1981

[Role of the contralateral cortex on the receptive field properties in the visual cortex of cats].

The aim of this series of experiments was to evaluate the receptive field properties of visual cells receiving part of their input the corpus callosum. Normal (control) and chiasma sectioned cats were recorded using conventional methods. The recording sites were the 17-18 border and the lateral suprasylvian (LS) cortex. The results indicated (a) the ocular dominance distribution was shifted towards the ipsilateral eye in the split chiasma cats; (b) orientation tunning and/or directional specificity were identical for the two eyes; (c) R.F. positions of binocular cells were also similar for each eye and were clustered near the vertical meridian, which they sometimes straddled; (d) R.F. sizes were larger in L.S. than in primary visual cortex but generally of equal dimensions for each eye. The results are interpreted with respect to the various functions which have been postulated for the corpus callosum.

Animals↗