Kitten Striate Cortex Research Articles

Stimulus for Rapid Ocular Dominance Plasticity in Visual Cortex

Although it has been known for decades that monocular deprivation shifts ocular dominance in kitten striate cortex, uncertainty persists about the adequate stimulus for deprivation-induced losses of cortical responsiveness. In the current study we compared the effects of 2 days of lid closure and 2 days of monocular blur using an overcorrecting contact lens. Our finding of comparable ocular dominance shifts in visual cortex indicates that deprived-eye response depression is not a result of reduced retinal illumination. The quality rather than the quantity of retinal illumination is the key factor for ocular dominance plasticity. These data have implications for both the mechanism and treatment of amblyopia.

Fluorescent two-dimensional difference gel electrophoresis and mass spectrometry identify age-related protein expression differences for the primary visual cortex of kitten and adult cat.

The recent introduction of fluorescent two-dimensional difference gel electrophoresis, combined with mass spectrometry, has greatly simplified the analysis and identification of differentially expressed proteins by eliminating intergel variability. In this report, we describe the successful application of this functional proteomics approach to compare protein expression levels in visual cortical area 17 of adult cats and 30-day-old kittens, in order to identify proteins expressed in an age-related fashion. We identified 16 proteins that were more abundantly expressed in kitten striate cortex and 12 proteins with a pronounced expression in adult cat area 17. Among those isolated from kitten area 17 were proteins related to axon growth and growth cone guidance and to the formation of cytoskeletal filaments. Glial fibrillary acidic protein, as identified in adult cat area 17, has been implicated previously in the termination of the critical period for cortical plasticity in kittens. In situ hybridization experiments for two of the identified proteins, glial fibrillary acidic protein and collapsin response mediator protein 5, confirmed and extended their differential expression to the mRNA level. Our findings show that two-dimensional difference gel electrophoresis combined with mass spectrometry is a powerful approach that permits the identification of small protein expression differences correlated to different physiological conditions.

Columnar distribution of serotonin-dependent plasticity within kitten striate cortex.

Recent studies have identified the potential for an important role for serotonin (5-HT) receptors in the developmental plasticity of the kitten visual cortex. 5-HT(2C) receptors are transiently expressed in a patchy fashion in the visual cortex of kittens between 30-80 days of age complementary to patches demarcated by cytochrome oxidase staining. 5-HT, operating via 5-HT(2C) receptors, increases cortical synaptic plasticity as assessed both in brain slices and in vivo. Herein, we report that bath application of 5-HT substantially increases the probability of long-term potentiation within 5-HT(2C) receptor-rich zones of cortex, but this effect is not observed in the 5-HT(2C) receptor-poor zones. Instead, in these zones, 5-HT application increases the probability of long-term depression. These location-specific effects of 5-HT may promote the formation of compartment-specific cortical responses.

Roles of N-methyl- d-aspartate receptors in ocular dominance plasticity in developing visual cortex: re-evaluation

We have re-examined whether N-methyl- d-aspartate receptors play a specific role in experience-dependent plasticity in kitten visual cortex. A specific antagonist of this glutamate receptor subtype, d, l-2-amino-5-phosphonovaleric acid, was directly and continuously infused into kitten striate cortex for one week concurrently with monocular lid suture. In the hemisphere infused with 50 mM antagonist, we found the usual shift in ocular dominance toward the open eye with only a few binocular cells remaining. The changes were accompanied by an extremely high incidence (38%) of abnormal cells lacking orientation selectivity across different ocular dominance groups. In kitten cortex infused with 10 mM antagonist concurrently with monocular deprivation for a week, recording from a drug-affected region near the infusion centre, we again found the U-shaped ocular dominance distribution with the high incidence of non-selective cells. In antagonist-infused, otherwise normal striate cortex of adult cats, we found that the proportion of binocular cells decreased by one-half in two cell populations: one recorded during the continuous infusion of 10 mM antagonist under general anaesthesia and paralysis and the other about two days after stopping the infusion. We also established that in vivo concentrations of chronically infused 10 mM antagonist decreased, not near-exponentially, but linearly with increasing distance from the infusion site. Thus, the effects of a directly and continuously infused concentrated antagonist of N-methyl- d-aspartate receptors on receptive-field properties of visuocortical cells are complex. The present findings strongly suggest that the antagonist effects in the developing cortex may be due primarily to blockade of normal synaptic transmission rather than specific disruption of an experience-dependent mechanism underlying ocular dominance plasticity.

Development of inhibitory mechanisms in the kitten's visual cortex.

The objective of this study was to evaluate the maturity of three inhibitory mechanisms (end-inhibition, side-inhibition, and cross-orientation inhibition) in the striate cortex of kittens at 4 weeks postnatal. To accomplish this, we made extracellular recordings from area 17 neurons while presenting visual stimuli consisting of sinusoidal luminance gratings or composites of gratings. We then compared data from kittens relating to various characteristics of each inhibitory mechanism with data from adults. We find that end-inhibition, side-inhibition, and cross-orientation inhibition are all present in kittens, and all show signs of maturity by 4 weeks postnatal. We conclude that the development of these inhibitory mechanisms occurs relatively early, and may coincide with the development of excitatory properties.

Formation of receptive fields in realistic visual environments according to the Bienenstock, Cooper, and Munro (BCM) theory.

The Bienenstock, Cooper, and Munro (BCM) theory of synaptic plasticity has successfully reproduced the development of orientation selectivity and ocular dominance in kitten visual cortex in normal, as well as deprived, visual environments. To better compare the consequences of this theory with experiment, previous abstractions of the visual environment are replaced in this work by real visual images with retinal processing. The visual environment is represented by 24 gray-scale natural images that are shifted across retinal fields. In this environment, the BCM neuron develops receptive fields similar to the fields of simple cells found in kitten striate cortex. These fields display adjacent excitatory and inhibitory bands when tested with spot stimuli, orientation selectivity when tested with bar stimuli, and spatial-frequency selectivity when tested with sinusoidal gratings. In addition, their development in various deprived visual environments agrees with experimental results.

Effects of intracortical infusion of anticholinergic drugs on neuronal plasticity in kitten striate cortex.

During a critical period of postnatal development the mammalian visual cortex is highly susceptible to experience-dependent alterations of neuronal response properties. These modifications are facilitated by the neuromodulators noradrenaline and acetylcholine. To identify the cholinergic mechanisms responsible for this facilitation, muscarinic and nicotinic antagonists were infused into the visual cortex of kittens while the animals were subject to monocular deprivation. Subsequently the ocular dominance of cortical cells was assessed by single-unit recording. Ocular dominance changes were suppressed by scopolamine and pirenzepine but not by gallamine, hexamethonium and mecamylamine. This blocking effect was concentration-dependent, and control experiments revealed that it was not due to suppression of neuronal responses to light. It is concluded from these results that acetylcholine facilitates neuronal plasticity in the visual cortex through mechanisms activated by muscarinic M1 receptors.

Development of binocular vision in the kitten's striate cortex

Studies of the development and plasticity of the visual pathway are well documented, but a basic question remains open: what is the physiological status of the system prior to extensive visual experience? Somewhat conflicting answers have been put forward, and in a major area, binocular vision, reports have ranged from severe immaturity to well-developed maturity. This is an important question to resolve since binocular cells in the visual cortex are thought to be the neural substrate for stereoscopic depth perception. We have addressed this question by recording from single cells in the striate cortex of kittens at postnatal ages 2, 3, and 4 weeks and from adults for comparison. Gratings with sinusoidal luminance distribution are presented to left, right, or both eyes. For each cell, we determine optimal values for orientation and spatial frequency. Relative phase (retinal disparity) is then varied in a dichoptic sequence so that binocular interaction may be studied. Results are as follows. In the normal adult, we have shown in previous work that most binocular interaction in the visual cortex can be accounted for on the basis of linear summation. Results from 3 and 4 week postnatal kittens are closely similar to those from adults. All types of binocular interaction found in adults are present in kittens. This includes phase-specific and non-phase-specific suppression or facilitation. Furthermore, monocular and binocular tuning characteristics are comparable in kittens and adults. The clear changes that occur with age are optimal spatial frequencies and peak responses. In addition, at 2 weeks, there is a substantially higher proportion of monocular cells compared to other ages and correspondingly, lower relative numbers of cells that exhibit phase-specific or suppressive binocular interactions. From increases in optimal spatial frequency and interpupillary distance with age, we calculated predicted changes in binocular disparity thresholds (stereo acuity) with age. Although there are methodological limits with respect to the behavioral testing of young kittens, the predicted results are comparable to some of the values obtained. Considered together, our results show that the physiological apparatus for binocular vision is functional at an early stage in postnatal development. It is possible that the connections that underlie this function are developed rapidly during early postnatal experience. An alternative possibility is that there is an elaborate genetic organization of binocular vision, but our study does not address this issue directly. A combination of these factors may be applicable.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of [formula omitted] on quisqualate-stimulated phosphoinositide hydrolysis in slices of kitten striate cortex

Stimulation of phosphoinositide (PI) hydrolysis by excitatory amino acids (EAAs) was studied in coronal slices of kitten visual cortex. Coincubation with N- methyl- d-aspartate (NMDA) markedly reduced the stimulation by quisqualate, however, this inhibition developed with a latency of > 10 min and occurred even when the NMDA exposure preceded, but did not overlap with,incubation in quisqualate. This time-course of NMDA inhibition of EAA-stimulated P1 turnover places new constraints on its possible mechanism of inhibition.

Rapid rearrangement of intrinsic tangential connections in the striate cortex of normal and dark-reared kittens: lack of exuberance beyond the second postnatal week.

Clustered intrinsic connections in the kitten striate cortex originate from an unclustered, diffusely organized pattern prevailing during the first postnatal week. We have studied the progress of this reorganization and its dependence on visual input by determining the topographies of the intrinsic tangential connections at various postnatal ages by means of axonal tracing methods. Neurons were labeled either by diffusion of the carbocyanin dye DiI in animals ranging in age between 1 day and 30 days, or by retrograde transport of fluorescent microspheres in animals ranging in age between 7 days and 11 months. Quantitative evaluation of retrogradely labeled neurons revealed that during the first postnatal week, intrinsic tangential connections are organized in an unclustered fashion. During the second postnatal week a rapid rearrangement of connections occurs and is complete around postnatal day 11. The main events taking place during the course of this rearrangement are a decrease in the density of tangential connections and an arrangement of them in a clustered fashion. Once the clusters have been formed, the periodicity of the clustered pattern of connections and the size and distinctness of the clusters do not change. This means that the system of clustered tangential connections is adult-like at the end of the second postnatal week. Dark rearing affects neither the rapid rearrangement of horizontal connections into an adult-like system of clusters, nor the integrity of this clustered topography until the end of the first postnatal month. The overall distribution and the lateral extent of the tangential connections remain about the same during the postnatal period and are not affected by dark rearing until the end of the first postnatal month. We conclude that the clustered system of tangential connections in the cat's striate cortex is determined innately.

The effect of short periods of monocular deprivation on excitatory transmission in the striate cortex of kittens: a current source density analysis.

The goal of this study was to assess changes in synaptic activity in the visual cortex of kittens following brief periods of monocular deprivation. Field potentials evoked by electrical stimulation of both optic nerves were registered in vertical penetrations through areas 17 and 18 of 4-5 week-old kittens which had been monocularly deprived for 2-7 days. In order to assess the laminar distribution of synaptic currents these field potentials were subjected to a current source density analysis. Current source density profiles elicited from the deprived eye differed from those induced from the normal eye in several respects: 1) The amplitudes of the responses showed considerable variation at different recording sites across the tangential dimension of cortex. 2) On the average, sinks and sources were markedly reduced, and this reduction was relatively more pronounced in non-granular than in granular layers. 3) However, in 30% of the tracks the layer IV sink showed no attenuation. It was reduced in 48% of the tracks and completely suppressed in 22% of the tracks. These results indicate that a substantial fraction of the deprived thalamocortical synapses remained functional, but that many of these synaptic events remained subthreshold. The significance of these findings is discussed in the context of recovery processes following reverse suture.

N-methyl-D-aspartate-evoked calcium uptake by kitten visual cortex maintained in vitro

As a functional measure of NMDA receptor effectiveness in kitten striate cortex, the uptake of 45Ca by visual cortical slices was measured after 2 minute bath applications of N-methyl-D-aspartate (NMDA). Significant Ca uptake occurred in response to 12.5-100 microM NMDA in slices prepared from visual cortex of normal animals aged 28-48 days. Basal uptake (in the absence of NMDA) was increased and evoked uptake was decreased in visual cortical slices prepared from age-matched dark-reared animals. Four days of binocular deprivation in otherwise normally reared animals had no effect on basal uptake, but significantly lowered NMDA-evoked Ca uptake at agonist concentrations greater than 25 microM. These data suggest that even brief manipulations of sensory experience are sufficient to alter visual cortical calcium regulation.

Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist

To assess the possibility that NMDA receptors play a special role in visual cortical plasticity, the selective antagonist 2-amino-5-phosphonovaleric acid (APV) was continuously infused into the striate cortex of kittens as the visual environment was manipulated during the critical period. The cortex was studied using single-unit recording from sites between 3 and 6 mm from the infusion cannulae. One week of D,L-APV infusion coincident with monocular deprivation or "reverse suture" produced a concentration-dependent increase in the percentage of neurons that (1) lacked normal orientation selectivity and (2) were responsive to stimulation of the deprived eye. These effects outlasted the presence of the drug in the tissue. APV treatment also prevented the acquisition of selectivity and visual responsiveness that normally results from monocular visual experience after dark-rearing. Lasting effects of chronic APV infusion were not observed in adult striate cortex. The effects of APV on kitten striate cortex depended on the presence of the D stereoisomer as infusion of L-APV was without effect. Estimates of extracellular concentration using 3H-APV indicated that significant effects could be obtained with concentrations as low as 20 microM D,L-APV. Recordings from units during infusion indicated that visual responses were reduced by APV. Nonetheless, a normal percentage of visually responsive neurons was found at sites greater than or equal to 3 mm from the infusion cannula. There was no evidence that chronic APV infusion affected the sampling frequency of recorded neurons or disrupted cytoarchitecture at the sites further than 3 mm from the infusion cannula. Taken together, the data indicate that the effects of APV on kitten striate cortex are likely due specifically to the blockade of NMDA receptors. These data are considered in relation to several hypotheses concerning the role of NMDA receptors in the experience-dependent development of striate cortex.

A Biochemical Correlate of the Critical Period for Synaptic Modification in the Visual Cortex

Stimulation of phosphoinositide hydrolysis by excitatory amino acids was studied in synaptoneurosomes of kitten striate cortex at several postnatal ages. Ibotenate and glutamate stimulated phosphoinositide turnover during the second and third postnatal months; N-methyl-D-aspartate and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) were without effect. The developmental profile of ibotenate-stimulated phosphoinositide turnover parallels the postnatal changes in cortical susceptibility to visual deprivation. The transient increase in ibotenate-stimulated phosphoinositide turnover does not occur in visual cortex of kittens reared in complete darkness.

Chronic recordings from single sites of kitten striate cortex during experience-dependent modifications of receptive-field properties.

1. With the use of chronically implanted floating microelectrodes, we obtained simultaneous single-unit recordings from multiple sites in the kitten striate cortex and followed experience-dependent modifications of receptive-field properties. For induction of experimental modifications, we used the paradigm of monocular deprivation and reverse occlusion. Kittens were implanted when 4-5 wk old. During the following 2 days, receptive-field properties of the recorded units were determined once under light ketamine anesthesia and repeatedly while the kittens were awake and only lightly restrained. Subsequently, one eye was patched, and the resulting changes in neuronal eye preference were followed by repeated measurements of response properties. For investigation of the effects of reverse occlusion, the deprived eye was opened and the previously open eye closed when the neurons had become unresponsive to the initially deprived eye. Alternatively, kittens were monocularly deprived for 1 wk by lid suture before implantation. The closed eye was then opened, the other eye patched, and the effects of reverse occlusion were studied for up to 1 wk by repeated measurements of receptive-field properties. 2. The earliest effect of monocular deprivation was the disappearance of binocular summation, i.e., binocular responses ceased to be superior over monocular responses. Overt changes of ocular dominance were observed as early as 6 h after the beginning of monocular deprivation. These consisted of a gradual decrease of the excitatory response to deprived eye stimulation and, on occasions, of an additional moderate increase of responses to the normal eye. A complete loss of excitatory responses to deprived-eye stimulation was seen as early as 12 h after occlusion. In numerous cells, however, stimulation of the deprived eye continued to evoke inhibitory responses even after excitatory responses had vanished completely. During this shift in ocularity, neurons preserved their orientation and direction selectively. 3. The minimal time required for the manifestation of ocular dominance changes was similar regardless of whether the animals were stimulated continuously or were asleep part of the time, suggesting the existence of an experience-independent consolidation period for ocular dominance changes. 4. The first change after reverse occlusion was a reduction of the response to the newly deprived eye. The time course of this inactivation was similar to that observed after initial deprivation, whereas the recovery of responses to the previously deprived eye had a considerably slower time course.(ABSTRACT TRUNCATED AT 400 WORDS)

Blockade of NMDA-receptors prevents ocularity changes in kitten visual cortex after reversed monocular deprivation

We investigated in the striate cortex of kittens whether the recovery from the effects of monocular deprivation that occurs after reverse occlusion requires activation of N- methyl- d-aspartate (NMDA) receptors. The right eye of 3–4-week-old kittens was closed by lid suture for one week. Subsequently this eye was reopened and the left eyelid sutured closed for another week. During this second week, the NMDA-receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), was infused from an osmotic minipump into the left visual cortex (50 nmol/h), while the right visual cortex was infused only with vehicle solution (saline) as control. At the end of the second week, the ocular dominance of striate cortical neurons was assessed with single unit recording. In the control hemispheres, the large majority of neurons was dominated by the newly opened eye, while in the APV-treated hemispheres most neurons were still dominated by the newly deprived eye. In addition, neurons in the APV-treated hemispheres were less responsive and showed a reduction of orientation tuning. These data confirm that chronic blockade of cortical NMDA-receptors disrupts the disconnection of deprived pathways after monocular deprivation and reduces both responsiveness and orientation selectivity of cortical neurons. In addition they indicate that blockade of NMDA-receptors prevents also vision-dependent recovery of deprived pathways after reverse occlusion.

Blockade of intracortical inhibition in kitten striate cortex: effects on receptive field properties and associated loss of ocular dominance plasticity.

We have investigated the importance of GABAergic inhibition for the receptive field properties and plasticity of cells in the visual cortex of kittens. Osmotic minipumps were used to continuously infuse the GABA-antagonist, bicuculline methiodide (BIC), into striate cortex. Extracellular recordings were made during BIC infusion to assess neuronal response properties during the blockade of inhibition. Recordings were also made from other kittens after concurrent monocular deprivation and BIC infusion to investigate the importance of response selectivity for ocular dominance plasticity. The minipump delivery technique was used to produce a large volume of cortex presumably free of GABA-ergic inhibition. Compared to recordings in saline-infused control hemispheres, about half of the cells in bicuculline-infused hemispheres had abnormally low orientation selectivity. The low selectivity was generally accompanied by marked anomalies in several other receptive field properties. Particularly striking was the large size of the receptive fields. At eccentricities less than 10 deg many receptive fields subtended from 10 to over 30 deg of arc. The less selective neurons also had abnormal responses to flashed stimuli, giving strong transient responses to the onset and offset of large stationary stimuli which filled their receptive fields. These results imply that intracortical inhibition normally suppresses responses to stimuli within a large excitatory zone beyond the classical receptive field. Inhibition is necessary for the normal orientation selectivity of many cells, although the selectivity may be partially established by the cell's excitatory input. Additionally, intracortical inhibition appears to be necessary for the antagonism and segregation of ON and OFF receptive field subregions. In our study of plasticity, we exploited the fact that BIC treatment greatly increases the range of stimuli that activate cortical neurons. Kittens were monocularly deprived for 7 days concurrently with cortical infusion of BIC. After cessation of the drug treatment, physiological recordings were made. Response properties had returned to normal but neurons in BIC-infused hemispheres had a significantly reduced ocular dominance shift compared to neurons in control hemispheres. This is probably related to the reduced selectivity of cells during BIC infusion. The suggestion here is that there is diminished ocular dominance plasticity in BIC-infused hemispheres because of an increased probability of correlated activity between spontaneous discharge from the closed eye and the cortical activity evoked by the open eye afferents.

Experience-dependent modifications of kitten striate cortex are not prevented by thalamic lesions that include the intralaminar nuclei.

It has been shown previously that surgical lesions of the antero-medial thalamus interfere with ocular dominance modifications that normally result from monocular deprivation in young kittens (Singer 1982). The aim of the present study was to determine whether this effect was due specifically to the destruction of the visual cortical projections of the anterior intralaminar nuclei. We report here that large excitotoxin lesions of the anterior dorsal thalamus have no effect on the cortical response to monocular deprivation. These data indicate that the intralaminar projection is not essential for ocular dominance plasticity.

Effects of monocular strobe rearing on kitten striate cortex.

Monocular deprivation in kittens does not lead to an ocular dominance shift in striate cortex if the visual stimuli do not contain contours. In the present study we sought to find out whether an ocular dominance shift is produced if the visual environment does contain contours but is devoid of motion. Six kittens were reared with one eye occluded in a visual environment that was lit only by the light of a stroboscope (2 flashes per sec). Exposure was started at 5-6 weeks of age after dark-rearing from birth and extended until 8-12 weeks of age for 8 h per day. The rest of the time was spent in total darkness. Thus, the animals were completely deprived of vision in one eye, while the other eye experienced only stationary flashing contours. Single units in area 17 of these animals were studied and compared to normally reared cats. In all six animals ocular dominance was clearly shifted towards the eye with strobe experience. The ocular dominance shift showed, however, the following interdependencies with other parameters: neurones that responded to stationary flashing test stimuli were nearly always dominated by the strobe eye; neurones that responded only to moving bars or edges remained binocular. In the normal control animals the ocular dominance distribution was similar for both groups of cells. Track analysis according to cortical lamination revealed that neurones in infragranular layers consistently showed a weaker OD shift towards the strobe eye than neurones in supragranular layers (including layer 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Blockade of "NMDA" Receptors Disrupts Experience-Dependent Plasticity of Kitten Striate Cortex

Intracortical infusion of the "N-methyl-D-aspartate" (NMDA) receptor blocker D,L-2-amino-5-phosphonovaleric acid (APV) renders kitten striate cortex resistant to the effects of monocular deprivation. In addition, 1 week of continuous APV treatment (50 nanomoles per hour) produces a striking loss of orientation selectivity in area 17. These data support the hypothesis that crucial variables for the expression of activity-dependent synaptic modifications are a critical level of postsynaptic activation and calcium entry through ion channels linked to NMDA receptors.