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The development of MK-801, kainate, AMPA, and muscimol binding sites in cat visual cortex.

Previous work using homogenate binding has shown that the development of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imin e maleate (MK-801) binding in cat visual cortex increases from 21 days to 42 days, the height of the plastic period, and decreases in adulthood. We have studied the generality of this finding by examining the development of NMDA binding sites in several brain regions and by examining the development of other binding sites in the visual cortex. After confirming the original finding, we extended it by showing that the sensitivity of MK-801 binding sites to glutamate and glycine decreases when the cat becomes an adult. We then examined the regional specificity of MK-801 binding. Retinal binding did not change significantly with age. Binding in both visual cortex and hippocampus increased significantly from 7 days to 42 days regardless of whether binding was measured per milligram wet weight or per milligram protein. The decline from 42 days to adulthood was less dramatic in the hippocampus than in the visual cortex and was statistically significant only when binding was measured per milligram protein. Saturation analyses also showed a difference in the two structures. Bmax in the visual cortex, but not in the hippocampus, decreased from 42 days to adulthood. To determine whether these developmental changes were specific to MK-801 binding sites, we compared the age-dependent binding of MK-801, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and muscimol. Like MK-801, kainate binding increased from 7 days to 42 days and decreased from 42 days to adulthood. AMPA and muscimol binding showed a similar increase in binding from 7 days to 42 days but did not decrease significantly from 42 days to adulthood. Displacement experiments suggest that AMPA and kainate bind to separate sites. The 42-day peak in NMDA and kainate binding suggests that their associated receptors may have a role in determining the plastic period of visual cortex.

Aging

Optimal spatial displacement for direction selectivity in cat visual cortex neurons.

Responses of single neurons in cat visual cortex were measured in response to sinewave grating stimuli. Firstly, a neuron's spatial frequency tuning was determined, and subsequent stimuli were set at the optimal spatial frequency for that neuron. Then a "jumping grating" stimulus was used: a sinewave grating subjected to a series of abrupt spatial displacements, while remaining stationary for a fixed exposure time between displacements. The amount of direction selectivity elicited by this stimulus was measured as a function of the amount of spatial displacement. Visual cortex neurons generally showed an optimal spatial displacement, corresponding to somewhat less than one quarter of a spatial period of the neuron's optimal spatial frequency (close to, but systematically less than, "quadrature phase"). In a majority of neurons tested, this optimal displacement was not affected by increasing the exposure time between displacements, indicating that the measurements were not a simple consequence of temporal frequency tuning. These results closely parallel recent human psychophysical data obtained from measurements of motion aftereffect or direction discrimination elicited by jumping grating stimuli.

Animals

Processes of visual recognition in monkeys and their neuronal correlates in the visual cortex: the influence of a blocker of M-cholinoreceptors.

The activity of individual neurons of the visual cortex was recorded simultaneously in behavioral experiments on monkeys before and after the systemic administration of a blocker of M-cholinoreceptors, amizil (0.8-1.0 mg/kg). The animals were trained to delayed visual differentiation of stimuli of various colors. After the administration of amizil, the characteristics of recognition deteriorated substantially: the duration of the storage of information in short-term memory sharply declined, while the time of the motoric reaction increased. The deterioration of these characteristics was accompanied by inhibition of the activity of the neurons of the visual cortex, inhibition which depended on the stage of recognition, and which intensified when there was an increase in the delay interval. The results obtained suggest that cholinergic mechanisms of the visual cortex are included in visual recognition, and apparently play various functional roles at various stages of behavior.

Animals

Sex and electroencephalographic synchronization after photic stimulation predict signal changes in the visual cortex on functional MR images.

PURPOSE: We evaluated factors that influence MR signal changes during photic stimulation of the visual cortex. We also tested the hypothesis that functional MR imaging response corresponds to electroencephalographic (EEG) synchronization after photic stimulation. METHODS: Thirty-eight healthy subjects, 20 men and 18 women, underwent photic stimulation of the visual cortex. They were studied with a 1.5-T MR unit, and photic stimulation was induced via 8-Hz LED goggles. Seven subjects with and seven without detectable functional MR imaging response to photic stimulation underwent further studies with 16-channel EEG after 2- to 30-Hz stroboscopic stimulation. RESULTS: Thirteen men and 18 women had a significant increase in MR signal in the visual cortex; seven men showed no visual cortex activation during more than two repeated studies. Six of seven volunteers with increased functional MR imaging signal after photic stimulation also showed signs of EEG synchronization when an 8-Hz stroboscopic flash was used; six of seven subjects with no functional MR imaging lacked EEG synchronization at 8-Hz stimulation. CONCLUSIONS: Men were more likely than women to have undetectable MR signal changes after photic stimulation. This finding should be considered when interpreting results of functional MR imaging studies. EEG with stroboscopic examination is a good predictor of functional MR imaging sensitivity to changes in regional cerebral blood flow induced by sensory stimulation.

Adult

Squint affects synchronization of oscillatory responses in cat visual cortex.

As shown previously, neurons in various areas of the cat's visual cortex respond to appropriate visual stimuli with oscillatory activity in the frequency range of 30-70 Hz. It has been suggested that synchronization of such responses serves to define assemblies of coherently active cells which represent individual visual objects. In this study, we have investigated this putative binding mechanism in the visual cortex of strabismic cats. We used six adult cats in which divergent squint had been induced surgically at the age of 3 weeks. Multiunit activity was recorded from area 17 with arrays of four or five closely spaced microelectrodes. Subsequently, auto- and cross-correlation functions were computed for all spike trains. To quantify the oscillatory nature of the responses and the strength of synchronization between spatially remote sites, damped sine wave functions were fitted to the correlograms. Analysis of responses obtained from 202 recording sites showed that the vast majority of cells had become monocular. Auto-correlation analysis revealed that the proportion of oscillatory firing patterns was similar to that observed in normal cats. However, cross-correlation analysis of 153 response pairs demonstrated that synchronization was reduced significantly between cells dominated by different eyes while it was as frequent and strong as in normal cats between cells dominated by the same eye. These findings indicate that strabismus not only causes a reorganization of afferent inputs but also affects intracortical interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Endstopped neurons in the visual cortex as a substrate for calculating curvature.

Neurons in the visual cortex typically respond selectively to the orientation, and velocity and direction of movement, of moving-bar stimuli. These responses are generally thought to provide information about the orientation and position of lines and edges in the visual field. Some cells are also endstopped, that is selective for bars of specific lengths. Hubel and Wiesel first observed that endstopped hypercomplex cells could respond to curved stimuli and suggested they might be involved in detection of curvature, but the exact relationship between endstopping and curvature has never been determined. We present here a mathematical model relating endstopping to curvature in which the difference in response of two simple cells gives rise to endstopping and varies in proportion to curvature. We also provide physiological evidence that endstopped cells in area 17 of the cat visual cortex are selective for curvature, whereas non-endstopped cells are not, and that some are selective for the sign of curvature. The prevailing view of edge and curve determination is that orientations are selected locally by the class of simple cortical cells and then integrated to form global curves. We have developed a computational theory of orientation selection which shows that measurements of orientation obtained by simple cells are not sufficient because there will be strong, incorrect responses from cells whose receptive fields (RFs) span distinct curves (Fig. 1). If estimates of curvature are available, however, these inappropriate responses can be eliminated. Curvature provides the key to structuring the network that underlies our theory and distinguishes it from previous lateral inhibition schemes.

Animals

Functional organization of lateral geniculate cells following removal of visual cortex in the newborn kitten.

When the visual cortex of a newborn kitten is removed, most neurons in the dorsal lateral geniculate nucleus degenerate, but a small population of large cells is spared. Electrophysiological recording revealed that detailed visual topography in the nucleus is abnormal and that single cells have unusually large receptive fields. These results suggest that optic axons deprived of their normal synaptic targets rearrange their connections to converge on local surviving neurons.

Animals

Distribution and morphology of functionally identified neurons in the visual cortex of the rat.

The distribution and morphology of functionally identified neurons were examined in the visual cortex of Long Evans pigmented rats. The results, based on qualitative and quantitative analysis of single cell spike activity, have shown that neurons in the rat visual cortex have well-defined receptive field properties and are similar to those reported for animals with more highly developed visual systems. Unlike the cat and monkey, the distribution of receptive field types appeared even throughout the visual cortex. Exception was provided by layer IV which, similar to the more 'visual' animals, contained the largest percentage of simple cells. Horseradish peroxidase injected into single, physiologically identified neurons allowed for detailed morphological characterization of functional cell types. Of the cells successfully filled with horseradish peroxidase, complex cells were pyramidal in morphology and located in layers II through VI. Simple cells were both pyramidal and non-pyramidal in appearance and were located in layers II + III and IV. Finally, hypercomplex cells were pyramidal in appearance and their perikarya were situated in layers II + III and V.

Animals

Amphetamine-induced recovery of visual cliff performance after bilateral visual cortex ablation in cats: measurements of depth perception thresholds.

After bilateral visual cortex ablation, cats exhibit a loss of depth perception as measured on a visual cliff, which recovers following administration of d-amphetamine. In this Study, 3 amphetamine-treated cats with visual cortex ablations showed a rapid and enduring recovery, with 2 of these animals obtaining levels of performance seen only with binocular vision, suggesting a restoration of binocular depth perception. Cats with asymmetrical lesions showed only a transient improvement during amphetamine treatment, and some animals not displaying autonomic signs of amphetamine intoxication did not improve. Saline-treated cats showed no signs of improvement, and the effect of amphetamine was blocked by the catecholaminergic antagonist haloperidol. These results indicate that amphetamine can induce an enduring recovery from a behavioral deficit after brain injury, which if left untreated would not spontaneously recover.

Amphetamine

Differential effects of quinolinic acid lesions on muscarinic acetylcholine receptors in cat visual cortex during postnatal development.

Quinolinic acid (QA) lesions of neurons in cat visual cortex were combined with conventional in vitro autoradiographic methods in order to define the cellular locus of the muscarinic acetylcholine receptor (mAChR). Animals of various postnatal ages had QA unilaterally injected into the visual cortex. Four to fourteen days later they were sacrificed and processed for electron microscopy (EM) or in vitro autoradiography. QA lesions at the various postnatal ages were found to eliminate intrinsic cortical neurons and their processes while leaving intact glia, fibers of passage and axon terminals from outside the lesion zone. Autoradiograms of visual cortex labelled with [3H]QNB (which labels M1 and M2 subtypes) showed an age-dependent loss of binding sites, with the greatest decreases occurring after 65 days postnatal. Examined separately, only the M1 mAChRs labelled with [3H]pirenzepine exhibited these age-dependent alterations. The results indicate a differential distribution of the M1 mAChRs during postnatal development. The loss of receptors late in postnatal life following QA suggests a dominantly neuronal locus; the relatively small loss early in postnatal life suggests a locus on other cellular elements.

Aging

[Differences in the properties of 2 groups of orientation detectors of the visual cortex in the cat].

Functional properties of 149 neurons in field 17 of the visual cortex were studied in immobilized cats. They were divided into two groups. In 37% of neurons the initial and peak latencies of responses changed not more than by 10 ms in the orientation range. They were named "timer"-neurons. 63% of neurons were called "scanners". "Timers" reliably differed from "scanners" in shorter latencies, time of the discharge frequency increase, duration of the response and higher discharge frequency in all stimuli orientations. Scanners had a higher orientation selectivity, they considerably more often scanned the range of orientations in time. Neurons of the two groups had contraphase dynamics of the width of tuning orientation during response while distribution of their preferential orientations supplemented each other. In orientation columns of the visual cortex, both timers and scanners were most often found with a predominance of the latter. The columns consisting of only timers or only scanners were more seldom. The role of differences in properties of two neuronal groups in the cat visual cortex for orientation detection is discussed.

Animals

How does the cerebral cortex work? Learning, attention, and grouping by the laminar circuits of visual cortex.

The organization of neocortex into layers is one of its most salient anatomical features. These layers include circuits that form functional columns in cortical maps. A major unsolved problem concerns how bottom-up, top-down, and horizontal interactions are organized within cortical layers to generate adaptive behaviors. This article models how these interactions help visual cortex to realize: (i) the binding process whereby cortex groups distributed data into coherent object representations; (ii) the attentional process whereby cortex selectively processes important events; and (iii) the developmental and learning processes whereby cortex shapes its circuits to match environmental constraints. New computational ideas about feedback systems suggest how neocortex develops and learns in a stable way, and why top-down attention requires converging bottom-up inputs to fully activate cortical cells, whereas perceptual groupings do not.

Attention

Muscarinic acetylcholine receptor subtypes in rat visual cortex--a comparative study using quantitative receptor autoradiography and in situ hybridization.

The laminar pattern of M1- and M2-muscarinic acetylcholine receptors (mAChR) in rat visual cortex has been compared with the distribution of the corresponding m1, m2, m3 and m4 receptor genes using both quantitative receptor autoradiography and in situ hybridization histochemistry. The laminar distribution of 3H-pirenzepine binding to M1-mAChRs in rat visual cortex shows a bimodal pattern with higher binding levels in upper layer III and deeper layer VI. In contrast, highest binding of 3H-AF-DX384 to M2-mAChRs was observed in upper layer IV (100%) and upper layer VI (about 80% of highest binding). The m1 receptor mRNA is almost homogeneously distributed throughout the visual cortex, whereas the m2mAChr mRNA predominates in layer IV with lower levels in layers I and V. The highest amounts of m3mAChR mRNA in rat visual cortex were observed in layer II, while the distribution of m4mAChR transcripts shows a bimodal pattern with peaks in layers III and upper layer VI. The distinct laminar pattern of mRNA muscarinic receptor subtypes in rat visual cortex suggest specific roles of the muscarinic receptor in visual function.

Animals

Evidence for a laminar organization of basal forebrain afferents to the visual cortex.

The present study shows that restriction of HRP injections to layer I within the visual cortex results in negligible retrograde labeling within the nuclei of the basal forebrain. In contrast, when the injections of either HRP or WGA-HRP are restricted to the granular and infragranular layers of visual cortex, extensive retrograde labeling occurs within the basal forebrain. Based upon these findings, we argue that the projection from the basal nucleus terminates preferentially within the deep layers of the visual cortex, and thus contributes minimally to the supragranular layers, including layer I.

Acetylcholinesterase

Involvement of nerve growth factor in visual cortex plasticity.

The physiological role of nerve growth factor (NGF), the prototype member of the neurotrophin family, has been widely studied. NGF has been shown to promote survival, sprouting and differentiation of sympathetic ganglion cells and sensory neurons in the peripheral nervous system; it has also been shown to support survival and regeneration of cholinergic neurons in the central nervous system. Recent evidence indicates that NGF is also involved in the neuronal plasticity of the visual cortex. Exogenous supplies of NGF have been shown to interfere with normal processes underlying activity- and age-dependent synaptic modifications in both developing and adult visual cortex. In parallel to these physiological effects, numerous neuronal markers in the visual cortex have been found to be influenced by NGF. Several proposals have been introduced to explain the physiological role of NGF in visual cortex plasticity. Although the mechanisms underlying NGF effects in the visual cortex are still under active investigation, current evidence implies that NGF, and perhaps other neurotrophins as well, may be useful for preventing or correcting inappropriate or anomalous connections in the visual cortex, and thus for treating visual dysfunctions such as amblyopia and strabismus.

Animals

Low-threshold Ca2+ channels mediate induction of long-term potentiation in kitten visual cortex.

1. The induction mechanism of long-term potentiation (LTP) in developing visual cortex was studied by recording intracellular responses from layer III-IV cells in slice preparations of kitten visual cortex at 30-40 days after birth. 2. Strong stimulation of white matter produced a late depolarizing response after an orthodromic action potential. This depolarizing response was abolished by membrane depolarization or hyperpolarization caused by current injection through the recording electrode. In addition, this response was reduced by bath application of a low concentration (100 microM) of Ni2+ without any changes in the rising slope of the excitatory postsynaptic potential (EPSP) or orthodromic action potential. This suggests that this response is mediated by low-threshold Ca2+ channels (LTCs). 3. The involvement of LTCs in the induction of LTP was tested. White matter was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes in EPSPs were tested by low-frequency (0.1 Hz) stimulation of white matter. Conditioning stimulation produced a large N-methyl-D-aspartate (NMDA) receptor-mediated depolarizing response in these cells, which obscured the presence of the late depoliarzation. Therefore the test was conducted in a solution containing an NMDA antagonist 2-amino-5-phosphonovalerate (APV). 4. Weak conditioning stimulation, which evoked no LTC responses, never induced LTP; whereas strong conditioning stimulation, which evoked LTC responses, always induced LTP. Strong conditioning stimulation failed to induce LTP when LTC responses were prevented either by membrane depolarization or hyperpolarization or by a bath application of 100 microM Ni2+. 5. In a solution without APV, the application of Ni2+ also prevented the induction of LTP. 6. When cells were impaled by an electrode containing a Ca2+ chelator 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), LTP was never induced, even though LTC responses were evoked by conditioning stimulation. These results indicate that Ca2+ influx into postsynaptic cells through LTCs induces the LTP. 7. The responses mediated by LTCs, which were evoked by the injection of current pulses into the cells, were maximum at the critical period of visual cortical plasticity, suggesting that LTCs in postsynaptic cells regulate the plastic changes in developing visual cortex.

2-Amino-5-phosphonovalerate

Test-retest analysis with functional MR of the activated area in the human visual cortex.

PURPOSE: To investigate the intersubject and intrasubject variability of the activated area in the visual cortex with functional MR imaging. METHODS: Double-section gradient-echo MR images were acquired at 1.5 T in 28 healthy volunteers using the fast low-angle shot (FLASH) technique. Visual stimulation was obtained with light-emitting diode (LED) goggles. Eighteen volunteers were studied twice. The size of the activated areas in the visual cortex and the increase in signal were measured. A reproducibility ratio for size (R[size]) and for location (R[overlap]) was calculated on a scale of 0.0 to 1.0. RESULTS: Activation was seen in 89% of the subjects. The size of the activated area was widely variable among subjects: mean, 460 +/- 284 mm2; range, 0 to 1029 mm2 in the first study in all volunteers. Signal increases ranged from 3.2% to 10.9%, with a mean of 6.6 +/- 1.7%. The mean values of intrasubject variability testing were R(size) = 0.83 +/- 0.16 and R(overlap) = 0.31 +/- 0.11. CONCLUSION: Functional MR imaging with the FLASH technique is useful in identifying certain cortical areas that have quite variable locations among subjects. This study provides reference data for the intrasubject and intersubject variability of the activation pattern of the visual cortex.

Adult

Interhemispheric synchronization of oscillatory neuronal responses in cat visual cortex.

Neurons in area 17 of cat visual cortex display oscillatory responses that can synchronize across spatially separate columns in a stimulus-specific way. Response synchronization has now been shown to occur also between neurons in area 17 of the right and left cerebral hemispheres. This synchronization was abolished by section of the corpus callosum. Thus, the response synchronization is mediated by corticocortical connections. These data are compatible with the hypothesis that temporal synchrony of neuronal discharges serves to bind features within and between the visual hemifields.

Animals