Chantal Milleret

The Sensitive Period for Strabismic Amblyopia in Humans

PURPOSE In order to assess the sensitive period for strabismic amblyopia, the period of susceptibility to monocular occlusion was investigated in 407 children who ranged in age from 21 months to 12 years. METHODS Patients were treated between 1975 and 1990 by occlusion of the best eye. The efficiency of the treatment was measured as the ratio of reduction of the amblyopia at the end of the occlusion. RESULTS The efficiency of the occlusion is shown to depend on the age of the onset of the treatment: recovery of acuity of the amblyopic eye was maximum when the occlusion was initiated before 3 years of age, decreased as a function of age and was about null by the time the patient was 12 years of age. CONCLUSION This is assumed to be an indication of the sensitive period for strabismic amblyopia in humans. The results are discussed on the basis of the neurophysiological mechanisms of amblyopia established in animals.

Morphology of Callosal Axons Interconnecting Areas 17 and 18 of the Cat

Seventeen callosally projecting axons originating near the border between areas 17 and 18 in adult cats were anterogradely labelled with biocytin and reconstructed in 3‐D from serial sections. All axons terminated near the contralateral 17/18 border. However, they differed in their diameter, tangential and radial distributions, and overall geometry of terminal arbors. Diameters of reconstructed axons ranged between 0.45 and 2.25 μm. Most of the axons terminated in multiple terminal columns scattered over several square millimetres of cortex. Thus in general callosal connections are not organized according to simple, point‐to‐point spatial mapping rules. Usually terminal boutons were more numerous in supragranular layers; some were also found in infragranular layers, none in layer IV. However, a few axons were distributed only or mainly in layer IV, others included this layer in their termination. Thus, different callosal axons may selectively activate distinct cell populations. The geometry of terminal arbors defined two types of architecture, which were sometimes represented in the same axon: parallel architecture was characterized by branches of considerable length which supplied different columns or converged onto the same column; serial architecture was characterized by a tangentially running trunk or main branch with radial collaterals to the cortex. These architectures may relate to temporal aspects of inter‐hemispheric interactions. In conclusion, communication between corresponding areas of the two hemispheres appears to use channels with different morphological and probably functional properties.

Pattern of Development of the Callosal Transfer of Visual Information to Cortical Areas 17 and 18 in the Cat

The aim of this study was to investigate the development of visual callosal transfer in the normally reared cat. Two‐ to nine‐week‐old kittens and adults (used as controls) underwent section of the optic chiasm. Three days later, the animals were placed under anaesthesia and paralysed; unit activities were recorded from visual cortical areas 17 and 18 and from the white matter in one hemisphere. The units were tested for their responses to visual stimulation of each eye successively. Out of 1036 recorded neurons, 185 could be activated through the eye contralateral to the explored cortex via callosal transfer. Most of them could also be driven through the ipsilateral eye via the ‘direct’ geniculo‐cortical pathway. For animals aged ≤2 weeks, virtually all of these units were located at the 17/18 border zone, with a majority in the supragranular layers. When activated through the corpus callosum, they displayed receptive fields located either on the central vertical meridian of the visual field or in the hemifield ipsilateral to the explored cortex. Such extension into the ipsilateral hemifield as well as receptive field disparities of binocular units decreased with age, while spontaneous activity, strength of response, orientation selectivity and ability to respond to slits moving at middle‐range velocity increased. The main conclusion is that the transient callosal projections described by anatomists, which are present until 3 months of age, do not achieve supraliminar synaptic contacts with parts of areas 17 and 18 other than the 17/18 border zone, at least from 12 days after birth. However the visual callosal transfer in young animals displays some characteristics which disappear with age.

Visual interhemispheric transfer to areas 17 and 18 in cats with convergent strabismus

Commissural connections between primary visual cortical maps of the two hemispheres are essential to unify the split representation of the visual field. In normal adult cats, callosal connections are essentially restricted to the border between areas A17 and A18, where the central vertical meridian is projected. In contrast, early convergent strabismus leads to an expanded callosal‐receiving zone, as repeatedly indicated by anatomical experiments. We investigated here the functional correlates of this widespread distribution of callosal terminals by analysing transcallosal visual responses in five anaesthetized and paralysed 4–10‐month‐old cats whose right eye had been surgically deviated on postnatal day 6. After acute section of the optic chiasm, single‐unit activity was recorded from A17 and A18 of the right hemisphere while the left eye was visually stimulated. A total of 108/406 units were transcallosally activated. While they were more frequent at the 17/18 border (46% of the units recorded within this region), numerous transcallosally activated units were located throughout A17 (16%), A18 (27%) or within the white matter (17%). In all regions, transcallosally driven units displayed functional deficits usually associated with strabismus, such as decreased binocularity and ability to respond to fast‐moving stimuli, and increased receptive field size. Many units also displayed reduced orientation selectivity and increased position disparity. In addition, transcallosal receptive fields were manifestly located within the hemifield ipsilateral to the explored cortex, with almost no contact with the central vertical meridian. Comparison with data from normal adults revealed that strabismus induced a considerable expansion of the callosal receiving zone, both in terms of the cortical region and of the extent of the visual field involved in interhemispheric transfer, with implications in the integration of visual information across the hemispheres.

Functional Selectivity of Interhemispheric Connections in Cat Visual Cortex

The functional specificity of callosal connections was investigated in visual areas 17 and 18 of adult cats, by combining in vivo optical imaging of intrinsic signals with labeling of callosal axons. Local injections of neuronal tracers were performed in one hemisphere and eight single callosal axons were reconstructed in the opposite hemisphere. The distributions of injection sites and callosal axon terminals were analyzed with respect to functional maps in both hemispheres. Typically, each callosal axon displayed 2 or 3 clusters of synaptic boutons in layer II/III and the upper part of layer IV. These clusters were preferentially distributed in regions representing the same orientation and the same visuotopic location as that at the corresponding injection sites in the opposite hemisphere. The spatial distribution of these clusters was elongated and its main axis correlated well with the preferred orientation at the injection site. These results demonstrate a specific organization of interhemispheric axons that link cortical regions representing the same orientation and the same location of visual stimuli. Visual callosal connections are thus likely involved in the processing of coherent information in terms of shape and position along the midline of the visual field, which may facilitate the fusion of both hemifields into the percept of a single visual scene.

Postural control in children with strabismus: Effect of eye surgery

The purpose of this study was to examine the postural control in children with strabismus before and after eye surgery. Control of posture is a complex multi-sensorial process relying on visual, vestibular and proprioceptive systems. Reduced influence of one of such systems leads to postural adaptation due to a compensation of one of the other systems [3]. Nine children with strabismus (4-8 years old) participated in the study. Ophthalmologic, orthoptic, vestibular and postural tests were done before and twice (2 and 8 weeks) after eye surgery. Postural stability was measured by a platform (TechnoConcept): two components of the optic flux were used for stimulation (contraction and expansion) and two conditions were tested eyes open and eyes closed. The surface area of the center of pressure (CoP), the variance of speed of the CoP and the frequency spectrum of the platform oscillations by fast Fourier transformation were analysed. Before surgery, similar to typically developing children, postural stability was better in the eyes open condition. The frequency analysis revealed that for the low frequency band more energy was spent in the antero-posterior direction compared to the medio-lateral one while the opposite occurred for the middle and the high frequency bands. After surgery, the eye deviation was reduced in all children and their postural stability also improved. However, the energy of the high frequency band in the medio-lateral direction increased significantly. These findings suggest that eye surgery influences somatosensory properties of extra-ocular muscles leading to improvement of postural control and that binocular visual perception could influence the whole body.

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

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

Comparative development of cell properties in cortical Area 18 of normal and dark-reared kittens

SummaryThe development of visual cell properties was studied in cortical Area 18 (A18) of normal (NRs) and dark-reared kittens (DRs), from 2 weeks of age to adulthood. In addition to the orientation selective (S) and non-selective (NS) cells, we describe a new type of non-selective cell with a peripheral zone (NSp), which could be either an intermediate form between NS and S cells and included in a sequential model or an immature form of the S cells whose responses are affected by peripheral stimulations. Using accurate coordinates for the area centralis position relative to the optic disc projection as a function of age, we show that: a) the extent of the visual field increases with age in DRs and NRs; b) the retinotopic organization is always present; c) receptive fields, large in the NS cells, reduce to the size of mature S cells as soon as the cells acquire orientation selectivity. This process can occur after only 6 h of visual experience; d) velocity preference shifts toward high velocities, though more so in NRs than in DRs. An interpretation of the development of these properties is proposed, taking into account eye growth, the growth of dendritic fields and the formation of new connections. A comparison with previous results obtained in Area 17 (A17) shows a similar time course of the specification (NRs) and of the despecification (DRs) processes, although the development of A18 is postponed by about 2 weeks. Moreover, the “adult-like” binocular distribution of ocular dominance depends upon visual experience in A18, while it does not in A17.

Role of eye movements in developmental processes of orientation selectivity in the kitten visual cortex

Six-week-old dark-reared kittens were exposed for 6 hr to a normal lighted environment in which they were free to move, but with eyes immobilized. Receptive field properties (orientation selectivity and ocular dominance) of the visual cortical cells (Area 17) were studied. No restoration of orientation selectivity could be observed when only the eyes were immobilized either by oculomotor nerve sections or by extraocular muscles removal, in contrast to what had been observed in intact free moving animals. From these results one can conclude that eye movements must be associated with vision to allow developmental processes of orientation selectivity in the primary cortex. These new results are compared to those obtained previously in paralyzed or restrained animals and those obtained in animals with interruption of orbital afferents.

Chapter 23 Reorganization processes in the visual cortex also depend on visual experience in the adult cat

Publisher Summary The chapter discusses that the reorganization process in the visual cortex also depend on visual experience in adult cat. This is illustrated with series of experiments. In a first series of experiments, it was considered that the receptive field (RF) sizes of visual cortical cells recorded in area 18, activated through the direct retino-geniculo-cortical pathway. The findings showed that a post-operative visual experience is necessary for a recovery to occur. In a second series, the RF characteristics of cells activated through the corpus callosum were analyzed after chiasmotomy. The results explain that monocular occlusion can induce an asymmetrical callosal transfer between visual cortical areas.