Biomedical subjects

M S Cynader

Publications and source records attributed to M S Cynader.

At least 73 records · Page 4Linked to original sources

PubMed1989

Phorbol 12,13-dibutyrate regulates muscarinic receptors in rat cerebral cortical slices by activating protein kinase C.

Stimulation of muscarinic acetylcholine receptors (mAChR) elicits phosphatidylinositol turnover, which yields inositol phosphates (InsP) and diacylglycerol (DG) the latter activating protein kinase C (PKC). Activating PKC with phorbol esters inhibits mAChR agonist-stimulated phosphoinositide hydrolysis and InsP production. A possible mechanism of this inhibition may be down-regulation of mAChR by PKC. In the present work, rat cortical slices were preincubated with phorbol 12,13-dibutyrate (PDBu) followed by binding assays for [3H]quinuclidinyl benzilate [( 3H]QNB), [N-methyl-3H]scopolamine [( 3H]NMS) or [3H]pirenzepine [( 3H]PZ). Our data demonstrate that activation of PKC by phorbol esters causes a rapid down-regulation of muscarinic cholinergic receptors. This down-regulation is also rapidly reversible. Receptors on the cell surface appear to be more sensitive to the effect of PKC than do internal ones. This down-regulation occurs by a decrease in the number of receptors, rather than by changes in receptor affinity. The results suggest that PKC may exert negative feedback on its own activation by down-regulating the receptors that normally elicit phosphatidylinositol turnover.

Animals↗

PubMed1989

Adaptation in single units in visual cortex: the tuning of aftereffects in the spatial domain.

Cat striate cortical neurons were investigated using a new method of studying adaptation aftereffects. Stimuli were sinusoidal gratings of variable contrast, spatial frequency, and drift direction and rate. A series of alternating adapting and test trials was presented while recording from single units. Control trials were completely integrated with the adapted trials in these experiments. Every cortical cell tested showed selective adaptation aftereffects. Adapting at suprathreshold contrasts invariably reduced contrast sensitivity. Significant aftereffects could be observed even when adapting at low contrasts. The spatial-frequency tuning of aftereffects varied from cell to cell. Adapting at a given spatial frequency generally resulted in a broad response reduction at test frequencies above and below the adapting frequency. Many cells lost responses predominantly at frequencies lower than the adapting frequency. The tuning of aftereffects varied with the adapting frequency. In particular, the strongest aftereffects occurred near the adapting frequency. Adapting at frequencies just above the optimum for a cell often altered the spatial-frequency tuning by shifting the peak toward lower frequencies. The fact that the tuning of aftereffects did not simply match the tuning of the cell, but depended on the adapting stimulus, implies that extrinsic mechanisms are involved in adaptation effects.

Adaptation, Physiological↗

PubMed1989

Adaptation in single units in visual cortex: the tuning of aftereffects in the temporal domain.

Adaptation-induced changes in the temporal-frequency tuning and direction selectivity of cat visual cortical cells were studied. Aftereffects were induced largely independent of direction. Adapting in either direction reduced responses in both directions. Aftereffects in the direction opposite that adapted were only slightly weaker than were aftereffects in the adapted direction. No cell showed any enhancement of responses to drifting test stimuli after adapting with moving gratings. Adapting in a cell's null direction usually had no effect. Dramatic differences between the adaptation characteristics of moving and stationary stimuli were observed, however. Furthermore, aftereffects were temporal frequency specific. Temporal frequency-specific aftereffects were found in both directions: adapting in one direction induced frequency-specific effects in both directions. This bidirectionality of frequency-specific aftereffects applied to the spatial domain as well. Often, aftereffects in the direction opposite that adapted were more narrowly tuned. In general, adaptation could shift a cell's preferred temporal frequency. Aftereffects were most prominent at high temporal frequencies when testing in the adapted direction. Aftereffects seemed to be more closely linked to temporal frequency than to velocity matching. These results constrain models of cortical connectivity. In particular, we argue against schemes by which direction selectivity is generated by inhibiting a cell specifically when stimulated in the nonpreferred direction. Instead, we argue that cells receive bidirectional spatially and temporally tuned inputs, which could combine in spatiotemporal quadrature to produce direction selectivity.

Adaptation, Physiological↗

PubMed1989

Vernier acuities of neurons in area 17 of cat visual cortex: their relation to stimulus length and velocity, orientation selectivity, and receptive-field structure.

The sensitivity of neurons in area 17 of the cat's visual cortex to vernier offset was expressed as the percentage reduction in response caused by the introduction of a given offset into a bar stimulus moving across the receptive field. There was a wide variation in sensitivity: in some cells response could be halved by an offset equal to a fifth receptive-field width (defined as twice the standard deviation of a Gaussian curve fitted to the response profile), while other cells showed no sensitivity. The highest absolute sensitivities of complex and simple cells were similar, although most cells with poor sensitivity were complex. Sensitivity was largely unaffected by changes in stimulus velocity and stimulus length, although there was a tendency for sensitivity to increase with decreasing bar length. Comparisons of orientation tuning curves with vernier tuning curves showed that the response to a vernier stimulus approximated the response to a single bar of the same overall length and an orientation equal to that of a line joining the midpoints of each bar. This was true for a wide range of sensitivity values. Vernier sensitivity was correlated with a measure of length summation H, which is positive when there is net facilitation between the bars, and negative when there is net inhibition. Vernier sensitivity was highest in cells with large values of H, and least in cells where H was negative. We examined a linear model of the simple cell receptive field which, together with a variable response threshold, was able to explain the correlation between vernier acuity and length summation. Although this model accounted qualitatively for many of our findings, the majority of simple cells had tuning curves that were sharper than the predicted ones. This suggests that there are nonlinearities in the behavior of many simple cells whose effect is to increase the sharpness of orientation tuning and consequently vernier sensitivity.

Animals↗

PubMed1988

Cellular and subcellular localisation of muscarinic acetylcholine receptors during postnatal development of cat visual cortex using immunocytochemical procedures.

A monoclonal antibody against the muscarinic acetylcholine receptor was used to study the distribution of this receptor within the cat visual cortex at the light and electron microscopic level. Immunolabelling was found to be distributed mainly in cell bodies and dendrites in both young and adult cats. The laminar distribution, however, changed during development from cortical layers IV and to a lesser extent II in kittens of 28-42 days of age into one favouring the upper (L I-III) and lower layers (L V and VI) in kittens and cats more then 60 days of age. Electronmicroscopy revealed staining of membranes of cell bodies and dendrites and a great amount of intra-cellular staining of vesicles and internal membranes. Since the receptors are found on cell bodies and dendrites in both kittens and adults this indicates that different populations of cortical cells express these muscarinic receptors at different postnatal ages.

Aging↗

PubMed1988

The effect of visual cortex lesions on vertical optokinetic nystagmus in the cat.

Vertical optokinetic nystagmus (VOKN) was measured before and after visual cortex lesions using the magnetic search coil technique. In normal cats, upward motion elicits higher slow phase gain than downward motion, especially at high stimulus velocities. Following decortication, the gain of upward VOKN may be attenuated by as much as 35% at stimulus velocities of 20% or more. This high velocity deficit in upward VOKN is consistent with the results of single unit studies of the lateral terminal nucleus (LTN) of the accessory optic system which suggest that visual cortical input (via the LTN) makes a direction specific contribution to the motion sensitivity of VOKN.

Animals↗

PubMed1988

The distribution and ontogenesis of [3H]nicotine binding sites in cat visual cortex.

In vitro autoradiographic techniques using [3H]nicotine were used to characterise nicotine binding sites in developing kitten visual cortex. These binding sites in adult animals have a Bmax of 3.91 fmol/mg protein and a Kd of 4.40 nM. Displacement experiments indicate that [3H]nicotine binds to a nicotinic receptor site that is similar to central nicotinic sites described by investigators in other mammals. The number of binding sites increases during postnatal development, peaking near 60 days of age and levelling-off thereafter. There is no evidence for large changes in affinity during postnatal development for this binding site. [3H]Nicotine binding sites are densely concentrated in layer IV in the visual cortex of adult animals, with sharply reduced binding outside of cortical areas 17 and 18. This laminar pattern does not change during postnatal development, but an increase in the number of binding sites in layer IV as well as in layers I and VI occurs during early postnatal life. These binding sites disappear when extrinsic cortical inputs are severed. However, they survive when neurons in the visual cortex are selectively destroyed with a cell-specific neurotoxin. Unilateral destruction of the lateral geniculate nucleus eliminates [3H]nicotine binding sites in the visual cortex ipsilateral to the lesion, suggesting that they are located presynaptically on the terminals of lateral geniculate nucleus afferent fibres. The laminar pattern of binding of [3H]nicotine during early development of the visual cortex is complimentary to that for muscarinic acetylcholine receptors. These latter receptors redistribute during postnatal development becoming less prominent in layer IV at the same time as the [3H]nicotine binding sites are increasing in number in this layer. For a short period of time at the height of the critical period for cortical plasticity, both populations of binding sites are located in layer IV.

Animals↗

PubMed1988

Transient concordant distributions of nicotinic receptors and acetylcholinesterase activity in infant rat visual cortex.

For a short period during the second week after birth, layer IV of rat visual cortex displays intense acetylcholinesterase (AChE) activity which demarcates area 17. We now report that this transient AChE pattern is paralleled by a marked increase in [3H]nicotine binding sites in layer IV of area 17. Muscarinic receptors show a different pattern. Neonatal bilateral enucleation results in a reduction of AChE reaction product and [3H]nicotine labelling in area 17, while leaving the pattern of muscarinic labelling virtually unaffected. The close association of [3H]nicotine labelling and AChE activity suggests that presynaptic nicotinic cholinergic receptors may modulate transmitter release while functional geniculocortical synapses are being formed.

Acetylcholinesterase↗

PubMed1988

Space-time separability of direction selectivity in cat striate cortex neurons.

The relationship between spatial and temporal factors underlying direction selective velocity tuning in cat striate cortex neurons was studied quantitatively using flashed and smoothly moving light bar stimuli. Responses to double-flash stimuli were obtained for all combinations of a series of spatial and temporal intervals between the two flashes. Nonlinear interactions underlying the unit's direction selectivity were estimated by subtracting the responses to the component single flashes. The extent of systematic interaction between spatial and temporal variables was assessed qualitatively, with contour plots, and quantitatively, by plotting the optimum displacement as a function of temporal separation. Both methods indicated interactions (space-time nonseparability) which were generally very small in magnitude, and uncorrelated either in magnitude or sign with the direction selective velocity tuning measured in the same neurons. These results demonstrate characteristic optimum spatial and temporal intervals for responses to the two-flash stimuli. The optimum spatial offset was independent of the temporal offset chosen, indicating space-time separability.

Animals↗

PubMed1988

[3H]nicotine binding sites are associated with mammalian optic nerve terminals.

The autoradiographic distribution of [3H]nicotine binding sites was examined in the superior colliculus in normal rats and cats, and in animals in which one or both eyes were removed. [3H]Nicotine binding sites in normal animals were densely concentrated in the superficial layers of the colliculus corresponding to the zone of termination of optic nerve fibers. Following bilateral enucleation, [3H]nicotine binding in the superficial collicular layers was drastically reduced. Unilateral enucleation markedly reduced [3H]nicotine binding sites in the colliculus contralateral to the removed eye, with little effect on the ipsilateral colliculus. These results provide further evidence that nicotinic acetylcholine receptors have a presynaptic location on optic tract terminals and may therefore modulate retinotectal transmission in both the rat and cat visual system.

Animals↗

PubMed1988

Direction-selective adaptation in simple and complex cells in cat striate cortex.

1. The selectivity of adaptation to unidirectional motion was examined in neurons of the cat striate cortex. Following prolonged stimulation with a unidirectional high-contrast grating, the responsivity of cortical neurons was reduced. In many units this decrease was restricted to the direction of prior stimulation. This selective adaptation produced changes in the degree of direction selectivity of the cortical units (as measured by the ratio of the response to motion in the preferred direction to that in the nonpreferred direction). 2. The initial strength of the directional preference of a given cortical unit did not determine the degree of direction-selective adaptation. Indeed, even non-direction-selective units could exhibit pronounced direction-selective adaptation. The degree of direction-selective adaptation was also independent of the overall decrease in responsivity during adaptation. 3. There was no difference between simple and complex cells in the total amount of adaptation observed. The selectivity of the adaptation, however, did differ between these two cell types. As a group, simple cells showed significant direction-selective adaptation, whereas complex cells did not. The directional preference of most simple cells decreased following preferred direction adaptation and many highly direction selective simple cells became non-direction selective. In addition, simple cells became significantly more direction selective following nonpreferred direction adaptation. 4. Some complex cells also demonstrated direction-selective adaptation. There was, however, much more variability among complex cells than simple cells. Some complex cells actually increased direction selectivity following preferred direction adaptation. These differences between simple and complex cells suggest that changes in direction selectivity following unidirectional adaptation are not due to simple neuronal fatigue of the unit being recorded, but depend on selective adaptation of afferent inputs to the unit. 5. The spontaneous activity of many cortical neurons decreased following preferred direction adaptation but increased following adaptation in the nonpreferred direction. The response to a stationary grating also decreased following preferred direction adaptation. However, there was very little change in the response to a stationary grating following adaptation in the nonpreferred direction.

Adaptation, Physiological↗

PubMed1987

Mechanisms for binocular depth sensitivity along the vertical meridian of the visual field.

By removing the visual cortex unilaterally, and recording along the intact 17/18 border, we have investigated the influence of the corpus callosum on the tuning curves for stimulus disparity of cat cortical neurons. Responses to binocular stimulation were examined to movement in the same (in-phase) and in the opposite direction (antiphase) across the two retinae. In lesioned cats, as in normal cats, units were encountered which showed high sensitivity and narrow tuning for stimulus disparity. In contrast to normal cats, however, lesioned cats showed a reduced proportion of units displaying moderate binocular interactions, as well as a substantial increase in disparity-insensitive cells. The loss of disparity sensitivity after decortication was associated with a reduced incidence of both selectivity for the direction of stimulus motion and binocular activation. No large differences between the preparations were seen, however, in the ocular dominance of the total populations of cells. Differences between the normal and lesioned cats were found in binocular responses to in-phase but not to antiphase stimulation motion. Tuning curves in lesioned cats showed reduced binocular inhibition but no changes in binocular facilitation. Our findings indicate that callosal input contributes to unit disparity sensitivity by enhancing direction-selective binocular inhibition. The corpus callosum generates disparity sensitivity in a population of units in the superficial cortical layers which may play a particular role in the perception of stereoscopic depth.

Animals↗

PubMed1987

Nicotine receptors are located on lateral geniculate nucleus terminals in cat visual cortex.

Using the methods of in vitro receptor autoradiography, we have characterized a population of receptors for nicotine in cat visual cortex that is concentrated primarily in layer IV of areas 17 and 18. Surgically undercutting the visual cortex essentially abolished [3H]nicotine binding in the isolated zone. However, neuron-specific, quinolinic acid lesions of a region of visual cortex had little effect on binding, establishing a presynaptic locus on cortical inputs for these sites. Lesions of the lateral geniculate nucleus abolished binding in the corresponding cortical areas, thus localizing the [3H]nicotine binding sites to lateral geniculate nucleus terminals in the cortex.

Animals↗

PubMed1987

Variability in hand surface representations in areas 3b and 1 in adult owl and squirrel monkeys.

Detailed microelectrode maps of the hand representation were derived in cortical areas 3b and 1 from a series of normal adult owl and squirrel monkeys. While overlap relationships were maintained, and all maps were internally topographic, many map features varied significantly when examined in detail. Variable features of the hand representations among different monkeys included a) the overall shapes and sizes of hand surface representations; b) the actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces, which commonly varied severalfold in area 3b and manyfold in area 1; c) the topographic relationships among skin surface representations, with skin surfaces that were represented adjacently in some monkeys represented in locations many hundreds of microns apart in others; d) the internal orderliness of representations; e) the completeness of representations of the dorsal hand surfaces; and f) the skin surfaces represented along the borders of the hand representation. Owl monkey maps were, in general, internally more strictly topographic than squirrel monkey maps. In both species, area 3b was more strictly topographic and less variable than was area 1. The degree of individual variability revealed in these experiments is difficult to reconcile with the hypothesis that details of cortical maps are ontogenetically specified during a period in early life. Instead, we propose that differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands. This conclusion is consistent with earlier studies of the consequences of peripheral nerve transection and digital amputation, which revealed that cortical maps are dynamically maintained and are alterable as a function of use or nerve injury in these monkeys (Merzenich et al., '83a,b, '84a; Merzenich, '86; Jenkins et al., '84; Jenkins and Merzenich, '87).

Afferent Pathways↗

PubMed1987

The accessory optic system of the monocularly deprived cat.

Single-unit extracellular recordings were made in the lateral (LTN) and dorsal (DTN) terminal nuclei of the accessory optic system (AOS) of 10 monocularly deprived cats. The separate effects of monocular deprivation (MD) observed in each hemisphere are outlined below. Unlike many units in normal animals, LTN and DTN cells in the hemisphere contralateral to the non-deprived (open) eye, were no longer activated through visual stimulation of the ipsilateral (deprived) eye. In both nuclei, cells were driven effectively only by stimuli presented via the contralateral eye. The distribution of preferred directions was considerably altered in the LTN but not in the DTN. Almost every LTN unit encountered in MD cats preferred downward stimulus motion, in contrast to normal animals where equal numbers of LTN cells show preferences for upward and downward movement (J. Neurophysiol., 51 (1984) 276-293). DTN units showed the usual preference for horizontal motion toward the recorded hemisphere. Velocity preferences were slower on average in the DTN, and unaffected in the LTN. In the hemisphere contralateral to the deprived eye, the ocular dominance distribution of LTN and DTN cells showed a distinct shift in favor of the contralateral (deprived) eye. This effect was not as complete as that observed in the other hemisphere. Cells in both nuclei displayed a small influence from the ipsilateral (exposed) eye in some animals, but this input was much less than that observed in normally reared cats. Average velocity preferences among DTN units were slower than normal, and slower relative to the DTN population in the opposite hemisphere. No pronounced changes were observed in LTN velocity tuning. The distributions of preferred directions for both nuclei were similar to those obtained in the other hemisphere: DTN cells were found to prefer horizontal motion, while most LTN units were activated best by stimuli moving vertically and down within their receptive fields.

Animals↗

PubMed1987

Laminar distribution of GABA-immunoreactive neurons and processes in area 18 of the cat.

Intracortical inhibition mediated by the neurotransmitter gamma-amino butyric acid (GABA) plays a crucial role in the formation of the physiological response properties of neurons in mammalian visual cortex. Using a potent antibody developed against the amino acid neurotransmitter. GABA (Immunoclear Co., USA), we have identified GABA-immunoreactive neuronal somata and processes in area 18 of the cat. The GABA-positive neurons included multipolar, bipolar and bitufted but not pyramidal cell types. The density of GABA-immunoreactive neurons was higher in Layers I-IV (range 182-205 cells/mm2) than in Layers V-VI (range 78-92 cells/mm2). The mean areal measurement of GABA-immunoreactive somatic profiles was 135 micron2 (s.d. = 66). We observed numerous GABA-immunoreactive fiber fragments predominantly in Layers I, III, IV and V. Most of the fibers were oriented with their long axis tangential to the cortical surface, but, vertically-oriented fibers were observed as well. Many of the fibers were axonal-like and appeared beaded in Layer I and occasionally in II, while most of the fibers in the other layers appeared myelinated. A dense GABA-immunoreactive neuropil was present in Layer V. Results from our studies provide immunohistochemical evidence for a system of GABA-immunoreactive neurons and axonal collaterals which presumably mediate inhibition in the visual cortex. Since many of the GABA-immunoreactive fibers were oriented tangential to the cortical surface, the structural elements required for inhibition between functional columns are present. GABA-mediated inhibition both within and between functional columns likely assists in the formation of receptive field properties in the visual cortex.

Animals↗

PubMed1987

Anatomical properties and physiological correlates of the intrinsic connections in cat area 18.

After making a map of response properties of neurons in a roughly 3 X 4 mm region of area 18 in the cat, we injected wheat-germ agglutinin horseradish peroxidase (WGA-HRP) and succinylated concanavalin A (Con A) into physiologically identified regions of the map. We observed up to 10 patches of retrogradely labeled cells surrounding each injection site. The majority of the patches occurred within 1.4 mm of the center of the injection site, but rare patches were found as far as 3.4 mm from the injection site. The mean center-to-center spacing of the intrinsic patches was about 1 mm, while the mean distance between the center of the injection site and the nearest patches was less than 1 mm. The labeled cells included both nonpyramidal and pyramidal types and were found in all layers, although they were usually most dense in layers II-IV. Between 2% and 9% of the cells within a cortical column were labeled after a single injection of WGA-HRP or Con A into area 18. Injections of different tracers into 2 neighboring areas resulted in a uniform and less patchy distribution of labeled cells, which suggests that the patches observed after a single injection were only a portion of a continuous horizontal system of interconnections. The patterns and positions of the intrinsic patches were compared to the distribution of the following receptive-field properties: preferred orientation, receptive-field location, and eye preference. The preferred orientations of the recording sites within the injected and labeled areas were different and, most frequently, orthogonal to each other. This is a highly specific projection, since regions with orientation values like those of the injection site were "within range," yet not labeled. We were unable to detect any relationship between the ocular preferences of the injected and labeled cell regions. Injections into areas predominantly driven by the contralateral eye resulted in labeled regions exhibiting varied eye preference distributions. In some animals they were like the injection site and in others there were equal numbers of contra- and ipsilateral eye-dominated regions. The overall distribution of the patches around the injection site was elongated along the anterior-posterior cortical axis of the brain. The patches extended further in the posterior than the anterior direction. These observations appear to be related to the finding that the cortical magnification factor is greater along the anterior-posterior than the medial-lateral axis of area 18.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

Functional topography in cat area 18.

Using closely spaced microelectrode penetrations, we have mapped the representation of the visual field and of several functional response properties on the surface of cat area 18. The representation of the visual field was anisotropic, with the magnification factor for vertical visual space being about 2-5 times greater than that for horizontal. The topographic anisotropy was paralleled by an anisotropy in the cortical point-spread function, a measure of the distribution in the cortex of cells with overlapping receptive-field centers. The spread of this distribution (measured as twice the standard deviation) was positively correlated with the magnification factor anisotropy, averaging about 0.6 mm along the mediolateral (M-L) axis and 1.2 mm along the anteroposterior (A-P) axis. Units with similar response properties were clustered across the cortical surface, but different response features were laid out in different ways. For units with orientations within a 90 degrees range, the clusters took the form of branching bands, with a center to center spacing of 1.25 +/- 0.13 mm. These bands ran from postero-medial to anterolateral across the cortical surface, roughly perpendicular to the 17/18 border. Units with similar preferred eye input were laid out in patches without a well-defined direction of elongation, and with a less well-defined periodicity that averaged 1.86 +/- 0.75 mm. Local correlations in direction preference extending over distances of 300 micron were found, together with frequent 180 degrees differences in the direction preferences of units close together. The organization of the map of orientation preference, and the way in which direction selectivity is overlaid on this map, is discussed in more detail in the accompanying paper (Swindale et al., 1987). No obvious structural relationships between the ocular dominance patches and the pattern of iso-orientation domains were observed. There were, however, obvious interrelationships between the topographic map and other functional response properties. The iso-orientation bands ran approximately perpendicular to the direction in which both the point-spread function and magnification factor were elongated. This will have the effect of maximizing the allocation of a full range of orientations by the cortex to each location in visual space.

Action Potentials↗