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M Cynader

Publications and source records attributed to M Cynader.

At least 55 records · Page 3Linked to original sources

Characterization, distribution, and ontogenesis of adenosine binding sites in cat visual cortex.

In vitro autoradiographic techniques were used to characterize binding sites for 3H-cyclohexyladenosine (CHA) and 3H-5'-N-ethylcarboxamidoadenosine (NECA) in cat and kitten visual cortex. 3H-CHA binding sites in adult cat have a Bmax of 1,363 fmol/mg protein and a Kd of 6.8 nM. Displacement experiments indicate that 3H-CHA binds to an adenosine receptor similar to the A1-adenosine receptor described by other investigators. 3H-NECA binding sites in adult cat have a Bmax of 518 fmol/mg protein and a Kd of 15.4 nM. Displacement experiments do not allow us to identify this binding site unambiguously. Bmax values increase during postnatal development for both binding sites, peaking in adulthood for 3H-CHA and at 30 d for 3H-NECA. Kd values show neither consistent nor significant differences during postnatal development for either binding site. 3H-CHA and 3H-NECA binding sites are concentrated in layers 1-3 and upper layer 5 in the visual cortex of adult cats. These laminar patterns, however, change during postnatal development, showing the densest binding in the deep cortical layers (5 and 6) in kittens younger than 30 d of age and a fairly homogeneous binding in older kittens before achieving the adult distribution.

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Modification of neurotransmitter receptor sensitivity in cat visual cortex during the critical period.

We have examined the characteristics of various receptors in cat visual cortex during postnatal development. These included beta-adrenergic, GABA, benzodiazepine and acetylcholine receptors. For each population of receptor the number (Bmax) and affinity (Kd) were examined as a function of postnatal age (3 days-adult). For all receptors examined, the Bmax increased during development from low early values to a peak within the critical period. The Kd also changed during development for most receptors. The simultaneous alterations in Bmax and Kd necessitate defining a term which takes both of these receptor properties into consideration. This term, called receptor sensitivity (RS), provides a more comprehensive measure of receptor function than either Bmax or Kd alone. Using this measure, we find that receptor sensitivity is low near birth for the 4 receptor populations studied, rises to a peak within the first two months of life, and then declines to near-neonatal levels for 3 of the 4 receptor populations.

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Alterations in the laminar distribution of pentagastrin binding sites in cat visual cortex during postnatal development.

The distribution and characteristics of [3H]pentagastrin (CCK-5) binding sites were examined in the visual cortex of cats of varied age. CCK-5-labelled binding sites in a highly age-dependent, laminar-specific manner. In young kittens, CCK-5 binding sites were found dominantly in layers IV-VI. During the first 3 months of postnatal development the laminar pattern of binding changed so that by 95 days postnatal, layers I-III and VI were the most densely labelled. CCK-5 binding sites appear to be members of a class of receptors which exhibit laminar alterations in their distribution during early postnatal development.

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Intrinsic projections within visual cortex: evidence for orientation-specific local connections.

The functional organization of intrinsic connections within area 18 of cat visual cortex was studied using combined electrophysiological and anatomical techniques. Physiological recordings were first used to map the distribution of orientation preference, ocular dominance, and receptive-field location relative to the cortical surface. Next, localized injections of lectin-conjugated horseradish peroxidase were made into physiologically identified regions within area 18. We found that (i) the local cortical interconnections are made preferentially between cell populations with orthogonal preferred orientations and are independent of the ocular dominance of the cortical cells, (ii) the map of visual space in the cortex is anisotropic with the magnification factor for vertical at least twice that for horizontal visual space, and (iii) the pattern of cortical projections compensates for the functional asymmetry so that a population of interconnected cells represents a roughly circular region of visual space.

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Characteristics and distribution of muscimol binding sites in cat visual cortex.

In vitro receptor binding techniques were used to study the characteristics and distribution of [3H]muscimol binding sites in cat visual cortex. [3H]muscimol, a specific GABA agonist, labeled a single population of binding sites with a Kd of 18 nM. Specific binding was saturable, reversible, and was blocked by the addition of GABA or (+)-bicuculline. Autoradiograms revealed that the highest density of [3H]muscimol binding sites occurred in cortical layer IV. Little variation between the various visual cortical areas was noted in contrast to marked regional heterogeneity within subcortical structures.

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Effects of neonatally induced strabismus on binocular responses in cat area 18.

Responses to binocular visual stimulation were compared in cortical area 18 of normal cats and in cats in which one eye was exodeviated by surgery early in postnatal life. In contrast to normal cats where most units (58%) were binocularly activated, relatively few units (10%) in strabismic cats were activated well by stimulation of either eye. Rather individual units were driven mainly via one eye or the other but not both. In addition, there was a tendency for more units to be driven well via the unoperated eye than via the exodeviated eye. Fewer cells preferring vertically oriented than horizontally oriented stimuli were found in area 18 of strabismic cats. This trend was observed for cells driven by either the normal or deviated eye and was especially marked among the small number of binocularly activated cells. Generally binocular responses and binocular interactions were found with stimulation at corresponding retinal points. In a few striking instances, however, the receptive fields of binocular neurons were located on noncorresponding retinal points at loci which would enable the cat to correlate the two images of an external object despite the large divergent strabismus. Quantitative responses to binocular stimuli presented at varied disparities and to stimuli with varied directions of motion in depth were compared in normal and strabismic cats. Despite the large strabismus, a reduced fraction of cortical neurons displayed substantial binocular interactions. In fact, binocular facilitation was as marked in the population of cells studied in strabismic cats as it was in normal animals. The major effect of strabismus was a reduction in the strength of binocular inhibition when units were tested with sideways motion. Disparity-specific responses to motion toward or away from the organism were little affected by strabismus. The degree of binocular facilitation and binocular inhibition among the cell population was similar in normal and strabismic cats. A subpopulation of units encountered in strabismic cats showed strong disparity-specific interactions for motion toward or away from the animal without equivalent modulation for sideways moving stimuli. Units with these properties were not found in normal animals and may, therefore, represent a special adaptation of the strabismic animals.

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Ontogenesis of muscarinic acetylcholine binding sites in cat visual cortex: reversal of specific laminar distribution during the critical period.

Acetylcholine appears to act as a modulator of neuronal activity in cat visual cortex and, like noradrenaline, may be involved with cortical plasticity mechanisms during the critical period. To explore possible ACh involvement in these mechanisms we have examined acetylcholine binding sites in cat visual cortex during development using [3H]QNB, a muscarinic antagonist. At 3 days postnatal [3H]QNB preferentially labelled binding sites in layer IV. During development the pattern of binding reversed, so that by 95 days postnatal layer IV was the least densely labelled. The number of binding sites increased during development peaking at 1 month postnatal. The Kd of [3H]QNB binding sites increased to 95 days postnatal, with a peak value of 0.76 nM. The results show that during development, and especially within the critical period, changes in [3H]QNB binding site distribution, number and affinity occur.

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Alterations in receptor number, affinity and laminar distribution in cat visual cortex during the critical period.

The number, affinity, and laminar distributions of various receptors in cat visual cortex were examined during postnatal development using homogenate and in vitro autoradiographic techniques. For all receptor populations examined, the total number of receptors (Bmax) increased from relatively low early values to peak values during the first three months of postnatal life followed by a drop or plateau in the number of receptors. This peak in Bmax occurred during the physiologically-defined period for cortical plasticity. For most receptors examined, the affinity (KD) was also altered during postnatal development. Many of the receptor populations examined exhibited changes in their initial laminar distributions during the first three months of postnatal development, although other did not. The results show a more complex picture of receptor ontogenesis than previously reported, and suggest that the observed receptor modifications affect the synaptic efficacy and the basic chemical circuitry of the visual cortex during the critical period.

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Ontogenesis of muscimol binding sites in cat visual cortex.

In vitro receptor binding techniques were used to study the characteristics, distribution, and ontogenesis of muscimol binding sites in cat visual cortex. [3H] Muscimol, a GABA agonist, labelled a single population of binding sites with a KD of 18 nM in adult cats. Specific binding was saturable, reversible and was blocked by the addition of GABA or (+) bicuculline. Autoradiograms revealed that the highest density of [3H] muscimol binding occurred in cortical layer IV. Similar patterns of [3H] muscimol binding were observed at all ages examined, although the binding densities differed. The peak [3H] muscimol binding density, corrected for amount of protein, occurred at 3 months postnatally. In 3 day old and adult cats binding density was 41% and 69%, respectively, of the peak value.

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Prolonged sensitivity to monocular deprivation in dark-reared cats: effects of age and visual exposure.

Previous studies have shown that the response properties of cortical cells of cats reared in darkness throughout the naturally-occurring critical period can still be modified by environmental manipulation. Here the effects of extremely prolonged dark-rearing, and of light exposure before or after dark-rearing on subsequent susceptibility to monocular deprivation are examined. Monocular deprivation remains effective in altering cortical ocular dominance even in cats which have been dark-reared for up to 2 years, long after the end of the naturally occurring critical period. The effects of monocular deprivation are, however, less pronounced in these cats than in animals dark-reared for shorter periods of time. The effects of visual exposure before dark-rearing were examined by allowing kittens 2 months of normal vision followed by 3 months of dark-rearing. Then, the effects of monocular suture were compared among these kittens and: (1) 2-month-old normal kittens (which had the same amount of visual exposure as the experimental animals); and (2) 5-month-old normal kittens (of the same age as the experimental animals). The results show that monocular deprivation is more effective in the experimental animals than in normal kittens of the same age, but less effective than in normal 2-month-old animals. The effects of visual exposure after dark-rearing were examined by allowing animals dark-reared for 4 months varied durations of binocular visual exposure before monocular suture. Susceptibility to monocular suture disappears about 6 weeks after the dark-reared animals are brought into the light.

Aging↗

Neurons in cat visual cortex tuned to the direction of motion in depth: effect of positional disparity.

We investigated sensitivity to the direction of stimulus motion in depth in neurons of cat visual cortex by using bar stimuli with different image velocities on the two retinae. These stimuli were presented at seven different retinal disparities (i.e. with different locations in depth). Approximately one-fourth of the neurons examined were sensitive to the direction of stimulus motion in depth. In general, the motion-in-depth tuning of these neurons was either unaffected by disparity or changed simply and systematically as a function of disparity, even when disparity was varied over the broad range of 12 degrees. In their relative indifference to disparity, the motion-in-depth neurons contrast with the units that are very selective to disparity and that respond best to sideways motion. Human equivalents to these two classes of units might provide a physiological basis for the distinction between binocularly-driven channels for motion in depth and for disparity (i.e. relative position in depth) that have been proposed on psychophysical grounds.

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Prior strabismus protects kitten cortical neurons from the effects of monocular deprivation.

The effects of 8 days of monocular eyelid suture beginning at 45 days of age were compared in normal kittens and in kittens which had been made strabismic by surgery early in life. In both groups of animals, monocular deprivation increased the relative strength of inputs from the non-deprived eye at the cortical level, but this effect was clearly less pronounced in the strabismic animals. The reduced effect of monocular deprivation in strabismic animals was observed mainly in the cortical hemisphere contralateral to the deprived eye.

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Adaptability of the vestibulo-ocular reflex to vision reversal in strobe reared cats.

Optical reversal of vision brings about adaptive changes in the vestibulo-ocular reflex (VOR) tending to reduce retinal image slip during head movement. The present experiments investigated this form of adaptation in cats whose complement of direction sensitive central visual cells had been substantially reduced by rearing in 8 Hz stroboscopic light. Horizontal vision reversal was produced by dove prisms carried in a skull-mounted mask. A scleral eye coil was used to measure horizontal eye movements. VOR gain and phase were measured in the dark during sinusoidal rotation using test stimuli of 1/8 Hz and 5- or 20 degrees/sec velocity amplitude. Initially, strobe reared cats produced virtually normal VOR in the dark, except for slight but significant exaggeration of the normal phase advancement to be expected at 1/8 Hz. Addition of their familiar strobe illumination produced almost perfect oculomotor compensation. Maintained vision reversal in both strobe and normal illumination produced similar patterns of adaptive change in normal and strobe reared subjects, i.e. all animals exhibited an initial fast, and subsequent much slower, stage of gain attenuation, with similar changes in phase. Thus, strobe rearing did not prevent the development of an essentially normal VOR, nor did it interfere significantly with the ability to adapt in response to vision reversal. Since strobe rearing depletes direction selective visual movement detectors in the cortex and superior colliculi, it is inferred that signals responsible for activating the adaptive process are probably carried mainly in the accessory optic, rather than cortical and collicular, visual system.

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Eye oscillations in strobe reared cats.

Cats reared from birth in stroboscopic illumination develop abnormal spontaneous eye oscillations of low amplitude. The present experiments were undertaken to define these eye movements as recorded in the dark, in stroboscopic light of various frequencies, after exposure to normal light and after attenuation of the vestibulo-ocular reflex (VOR) gain by optical reversal of vision. The interaction of spontaneous eye oscillations with voluntary saccadic eye movements, and optokinetic tracking (OKN), were also studied. Two cats, reared from birth to 18 months in 8 Hz strobe light, and one normally reared control animal, were used. Horizontal movement of the right eye was measured by the scleral eye coil method. The frequency content of eye movement records was determined by power spectral analysis. VOR gain was estimated in the dark, by rotating the animals sinusoidally at 1/8 Hz and 5 degrees/sec velocity amplitude. In the dark, both strobe reared cats had abnormal spontaneous eye oscillations at a frequency close to 8 Hz, with peak-to-peak amplitudes of 0.5--1.0 degrees. These abnormal eye movements did not interfere with, nor were they abolished by, normal oculomotor activity. The introduction of strobe light modified the spontaneous eye movements by entraining the oscillations at a given 'forcing' frequency, and by producing a number of harmonics or sub-harmonics. In one of the strobe reared animals, the effect of normal light was to reduce the characteristic 'dark' value of 9 Hz, to a new maintained 'light' value of 2.7 Hz. Adaptive attenuation of the VOR gain caused the abolition of regular spontaneous eye oscillations in the dark; nevertheless, transient oscillations to single strobe flashes could still be elicited in the VOR adapted condition. The results are interpreted as representing an organised attempt by the developing oculomotor system to attain the goal of stable visual perception in a new visual environment.

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