Loss of spatial resolution of lateral geniculate nucleus neurones in kittens raised with convergent squint produced at different stages in development

Summary In twelve kittens, convergent squint was surgically produced at either 3, 6, 8, 10, 13, or 16 weeks. When these kittens reached the age of 4–8 months, the spatial resolution of sustained cells which received inputs from the area centralis in layers A and A1 of both the left and right lateral geniculate nucleus (LGN) was measured under nitrous oxide/halothane anaesthesia, using the highest spatial frequency of a sinusoidal grating resolved by cells as a measure of cellular visual acuity. Spatial resolution of cells fed by the squinting eye's area centralis was poorest in the kittens in which the squint was produced at 3 weeks. The resolution of the cells driven by the area centralis of the squinting eye gradually improved for the kittens in which the squint was produced at progressively later stages. There was no effect of convergent squint on the resolving power of cells in the kittens in which squint was produced at 13 weeks and 16 weeks. The developmental curve of spatial resolution of LGN cells obtained from normal kittens of different ages was found to fit very closely with a plot of the spatial resolution of cells driven by the squinting eye against age at squint production. These results suggest that the loss of spatial resolution (amblyopia) in the eye with convergent squint is due to the arrest of development of spatial resolution during the sensitive period in early postnatal life. Clinical implications are discussed.     

Spatial frequency thresholds of single striate cortical cells in neonatal corpus callosum sectioned cats

Summary Following section of the corpus callosum at 1–6 postnatal weeks in cats, behavioral visual acuity was measured binocularly and monocularly from 6–29 postnatal weeks; physiological determination of spatial frequency thresholds of single striate cortical cells was performed when the cats were at least 8 months old. Results were compared between cats with callosum section at each postnatal week, as well as with normal cats. Cats with callosotomy at 1–3 postnatal weeks had deficits in behavioral visual acuity, and the deficits were greatest in the youngest operated cats. Cats with callosotomy at 1–2 postnatal weeks failed to resolve as high spatial frequencies as did normal cats, and the resolution of the 1 week operated cats was lower than the resolution of the 2 week operated cats. Cats with callosotomy at 3–6 postnatal weeks had spatial frequency thresholds that were equivalent to those of normal cats. To determine what kinds of striate cells had reduced spatial resolution following neonatal corpus callosum section, cells were categorized according to class (Simple, Complex), receptive field location (Central, Peripheral), and monocular behavioral acuity eye performance (Better Eye, Worse Eye). Cats with corpus callosum section during postnatal week 1 had the lowest spatial resolution for all cell categories compared to all groups tested. However, cats with callosum section during postnatal week 2 had normal spatial frequency thresholds for Simple, Central and Better Eye categories. The cats with callosum section in postnatal weeks 3–6 had normal spatial frequency thresholds for all cell categories. For corpus callosum sectioned cats with and without visual deficits, and for normal cats, visual acuity measured behaviorally is significantly related to visual acuity measured physiologically. The results show that neonatal corpus callosum section in cats can affect behavioral visual acuity, as well as the spatial frequency thresholds of many categories of striate cortical cells. However, callosum section at different ages affects different populations of cortical cells. Furthermore, the results suggest that neonatal corpus callosum section may directly affect a single fundamental property of cells in primary visual cortex with a resulting disruption of many visual functions.     

An electrophysiological study of a transient ipsilateral interpositorubral projection in neonatal cats

Summary We examined whether transient projections in the developing central nervous system of Mammalia form functional synapses on their target neurons, using transient ipsilateral interpositorubral (iIR) projection in kittens as a model system. Intracellular recordings were made from red nucleus (RN) neurons in 26 kittens aged 6–26 postnatal days (PD6-26). RN neurons were identified by monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by stimulation of contralateral nucleus interpositus (IN), and additionally by intracellular staining in a few cells. Sixty-nine out of 362 RN neurons responded to stimulation of the ipsilateral IN. Of the 69 cells, 25 showed depolarizing responses with relatively short latency (2.1–6.7 ms) in kittens up to PD20. Such responses were not observed in older animals. Varying stimulus strength revealed that the potentials were unitary. Paired-pulse facilitation of the potential was observed, suggesting that the depolarizations are EPSPs. Several lines of evidence were obtained suggesting that the EPSPs are evoked monosynaptically. They followed high-frequency stimulation up to 50 Hz, and their latencies remained constant with varying stimulus strength. The latencies of ipsilaterally induced EPSPs were always longer than those of contralateral ones, evidence consistent with the longer course of ipsilaterally projecting axons than that of contralateral ones (Song and Murakami 1990). The age of disappearance of the monosynaptic EPSPs, i.e., PD20, also corresponds roughly with that of the anatomically demonstrable iIR fibers (PD15–PD25; Song and Murakami 1990). It is thus concluded that the transient iIR fibers in kittens form functional synapses on RN neurons.     

Postnatal development of somatostatin-containing neurons in the visual cortex of normal and dark-reared rats

Summary The distribution of somatostatin (SRIF)-immunoreactive neurons in the visual cortical areas 17, 18 and 18a of Wistar rats from birth to adulthood was followed in both normal and dark-reared animals. The SRIF neurons show difference in distribution amongst the three cortical areas studied as early as the first postnatal week. Area 17 was distinguished by fewer SRIF cells in the upper layers (I–III), which results in a lower overall density. The SRIF neurons in all areas appeared to increase in numbers up to about 3 weeks and then decline dramatically to adult levels, which were 14–19% of the peak levels. Although this decline was still obvious, it moderated to 25–31% in dark-reared animals. The greatest effect was seen in area 18 where, at 60 days of age, there were twice as many SRIF cells in darkreared as in normal controls. It is suggested that, under conditions of dark rearing, the overall pattern of development of SRIF neurons, being uninfluenced by extrinsic factors, reveals the cells' genetic potential.     

Profile of the sensitive period for monocular deprivation in kittens

Summary Thirteen kittens were subjected to 10–12 days of unilateral eye closure at ages spaced regularly through the first 4 months after birth. At the end of each kitten's period of monocular vision, the degree of functional disconnection between the deprived eye and neurons in striate cortex was assessed by means of single-unit recording. When the proportion of cortical cells giving no response to stimulation through the deprived eye was analyzed as a function of the kitten's age at the onset of eye closure, it was found that the effectiveness of monocular deprivation rose prior to postnatal day 28, remained high through day 48 and then subsided gradually, probably persisting at least through the end of the fourth postnatal month. The degree of functional modifiability persisting in the visual cortex of older kittens may be related to the initial ocular dominance of each neuron. Cells responsive exclusively to the deprived eye prior to deprivation probably do not acquire functional input from the nondeprived eye in kittens older than 48 days, for a normal proportion of such cells is encountered after the period of eye closure. Conversely, cells dominated by the nondeprived eye probably are most likely to lose their input from the deprived eye, as indicated by the columnar organization of cells not responsive to the deprived eye.This work was supported by Grant EY01175 and Research Career Development Award EY00092 from the National Eye Institute to R.D.F. A National Institutes of Health Training Grant, GM0748-03, helped to support C.R.O.     

Properties of LGN cells in kittens reared with convergent squint: A neurophysiological demonstration of amblyopia

Summary The spatial resolution of LGN cells has been studied in 4–5 month old kittens raised with convergent squint surgically produced in one eye at the age of 3–4 weeks. The sustained cells which received inputs from the central retina of the squint eye showed significantly poorer spatial resolution (determined by the highest spatial frequency of a sinusoidal grating to which a cell responded with modulated firing) than those which received inputs from the central retina of the normal eye. The spatial resolution of cells which received inputs from the peripheral retina of the squint eye was not different from that of cells receiving inputs from the peripheral retina of the normal eye. The visual latency of sustained cells which received an input from the area centralis of the squint eye was considerably lengthened and the response showed a sluggish onset. Thus the most important clinical symptom of amblyopia, namely the reduction of foveal visual acuity, has been demonstrated in kittens raised with unilateral vonvergent squint. The results suggest that the lesion responsible for amblyopia due to squint might be a functional degeneration of the high spatial frequency tuning cells in the pathway prior to the visual cortex, i.e. in the retina or LGN.This work was supported by grants from the Medical Research Council G 969/618 B, the Royal National Institute for the Blind, and from St. Thomas's Hospital to establish a cat colony.     

Postnatal X-ray irradiation effects on glomerular layer of rat olfactory bulb: quantitative and immunocytochemical analysis

Summary In the rat olfactory bulb, the majority of interneurons in the glomerular layer (GL) are supposed to be generated during first postnatal week. Low and repeated doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to impair the development of interneurons. The resulting effects on olfactory bulb neurons were examined stereologically and immunocytochemically in animals of 4 and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL decreased to 55% (1200 rad) – 70% (800 rad) of control, 2) numerical cell densities in GL decreased to 40% (1200 rad) – 60% (800 rad) of control, thus resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) – 40% (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In comparison, mitral cells, which are generated prenatally, were much less affected (total cell number: 70–80% of control), indicating a selective loss of cells generated during the first postnatal week in GL. Effects on somata and processes immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old rats. All of these immunoreactive elements showed a drastic decrease in all layers. Semiquantitative analysis showed that in the GL, calbindin D-28K immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is, TH(+) and GABA(+) neurons decreased to 20% (1200 rad) – 40% (800 rad) of control, whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) – 30% (800 rad) of control in the GL of irradiated bulbs. These findings indicated that larger proportions of calbindin D-28K(+) neurons might be generated during the first postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These observations suggest that the majority of GABA(-)TH(+) neurons were less affected by X-ray irradiation during the first postnatal week and thus that they might be generated in the prenatal period. Since during the first 2 postnatal weeks, neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change their phenotype at some postnatal developmental period.     

Behavioural studies of spatial vision in cats reared with convergent squint: Is amblyopia due to arrest of development?

Summary Visual acuity and contrast sensitivity were measured behaviourally in normal adult cats and cats reared with monocular convergent squint from 3, 6, 8, 12, and 24 weeks of age. The visual acuity of the squinting eye was significantly lower than that of the non-squinting eye in cats with squint from 3, 6, and 8 weeks of age. No significant difference in acuity between eyes was found in the 12- and 24-week squinting cats and in the controls.Contrast thresholds at all spatial frequencies tested (range 0.13–2.0 c/ °) were higher in the squinting eye than in the non-squinting eye of cats with squint from 3 and 6 weeks of age, but differences were greater at the higher spatial frequencies. In the 8-week squinting cat, contrast thresholds were increased only at higher spatial frequencies. No significant differences in contrast sensitivity were found in the cat with squint from 24 weeks of age and in the controls.The degree of disturbance of spatial vision in squinting cats was most related to the age at onset of the squint, i.e., the earlier the onset, the more profound the amblyopia. The period of susceptibility extended from about 3 to 12 weeks of age. When compared with data on the development of visual acuity in kittens, the pattern of results from the present study suggests that convergent squint can arrest the development of spatial vision.This work was supported by the M. R. C.     

Functional properties of auditory-nerve fibers during postnatal development in the kitten

Summary The discharges of the auditory-nerve fibers were studied in kittens between 2–40 days of age. Up to the 10th postnatal day, fibers could be divided into two main categories: (1) fibers with spontaneous activity (SA) that respond to sound and (2) fibers without SA but with evoked responses. A third, smaller, category, fibers having neither SA nor evoked activity, was also present. The development of SA comprises two phases. The first, lasting from birth up to the third postnatal week, shows a relatively fast increase and the second, lasting up to adulthood, a slower increase. Typical tone burst responses can be recorded at the end of the first postnatal week. Thereafter reactivity steadily increases especially after the 10th postnatal day. In young animals, rate level function is characterized by a steep segment with a low dynamic range followed by a decrease in activity that lasts until the end of the second week. At this point adult-like functions may be observed, although maximal firing still increases for some weeks. Tuning curves and threshold sensitivity tend to develop inversely at corresponding frequencies. Fibers with low characteristic frequencies reach adult threshold before that of high frequency fibers and high frequency fibers reach adult tuning before low frequency fibers. A comparison of auditory-nerve fiber activity in kittens show that maturation of most functional characteristics lasts several weeks after birth and in some cases continues after the first postnatal month.     

Effects of Divergent Strabismus on the Horizontal Connections of Neurons in the Cat Visual Cortex

Neuron connections of eye dominance columns in the visual cortex were studied in kittens at age 5–6 months with experimental strabismus induced on days 13–16 of life (by tenotomy of the medial ocular muscle). A photographic method was used to assess the angle between the visual axes of the eyes. The operated oculomotor muscle was found to undergo partial reattachment to the eyeball. In some kittens, the operated eye returned to the normal position, while others showed persisting deviation of the eyes by 5–15°. Loss of the binocular properties of cortical neurons have been demonstrated in such animals (Sireteanu et al., 1993). Differences were seen in the extents of connections of cortical eye dominance columns between these groups of cats. Elimination of diplopia and non-correspondence of the two retinal images in kittens of these groups is suggested to be mediated by different mechanisms: alternation of the eyes on fixation or suppression of the activity of the deviant eye.     

Development of X- and Y-cells in kittens

Summary A contrast reversal stimulus was used to classify the retinal ganglion cells of kittens 3–12 weeks of age. At 3 and at 4 weeks of age, the majority of the units were classified as Y-cells. The percentage of X-cells was similar to that of the adult at 5–6 weeks of age although other response properties were not adult-like. The angular size of the receptive field center was significantly larger than that of the adult through 5–6 weeks of age. An estimate of the position of the vertical meridian was obtained from the positions of the receptive fields in the visual field which permitted the calculation of the posterior nodal distance in kittens of various ages. From the posterior nodal distance, the linear extent of the receptive field center was determined. This showed that there is only a very slight increase in the linear size of the receptive field center from 3 weeks to adulthood.     

Perisomatic changes in the maturing hypoglossal nucleus after axon injury

Summary The perisomatic retrograde reactions to peripheral nerve injury during postnatal maturation were investigated by quantitative light and electron microscopy. The hypoglossal nerve was crushed, ligated or transected in 10 and 21 day postnatal (dpn) rats. Only crush injury was made in 7 dpn rats. Survival periods ranged from 3 to 40 days postoperative (dpo). Normal and sham operated animals of corresponding ages served as controls. A remarkable, transient response of neuronal somata in the young (7–10 dpn) rats, following all three types of axon injury, was the formation of excrescences which engulfed neuronal processes: boutons, dendrites, small neurites and a few myelinated axons in adjacent neuropil. The somal engulfment was rarely evident after nerve injury to 21 dpn rats. Bouton displacement from the somal surface, accompanied by glial incursion, followed each type of nerve injury but was less extensive and occurred later in the young rats. There seemed to be no association in the amount of boutons displaced from neuronal somata with the type of nerve injury for any of the three experimental age groups. However, the rate and intensity of the perineuronal glial reaction were related to the severity of the nerve injury in the older (21 dpn) but not in the younger (7–10 dpn) rats. Substantial loss of neurons occurred in the affected nucleus after each type of trauma to the young neurons. The degree of neuronal loss was related to the age and the volume of axoplasm disrupted. Only nerve transection in 21 dpn rats resulted in appreciable neuronal loss. The responses of axotomized neurons, their afferent axon terminals and the surrounding glia are quantitatively and qualitatively different in the hypoglossal nucleus of rats of increasing postnatal ages.     

Spontaneous and evoked hypothalamic unit activity in kittens during development

Spontaneous and evoked hypothalamic unit activity in response to sensory stimuli was studied in acute experiments on anesthetized kittens. After the second day of postnatal development, spontaneous unit activity can be recorded in the posterior hypothalamus. Evoked responses to sciatic nerve stimulation were recorded on the fourth to fifth day after birth. In the early stages of development phasic and tonic types of unit responses are present in the hypothalamus, with some predominance of phasic. At the end of the third week responses of hypothalamic neurons in kittens have still not reached their definitive formation.Translated from Zhurnal Évolyutsionnoi Biokhimii i Fiziologii, Vol. 12, No. 2, pp. 169–176, March–April, 1976.     

The postnatal development of visual callosal connections in the absence of visual experience or of the eyes

Summary Counts of callosal neurons retrogradely labeled by horseradish peroxidase (visualized using multiple substrates) were obtained in areas 17 and 18 of five kittens reared with their eyelids bilaterally sutured and of three kittens which had undergone bilateral enucleation on postnatal days 1–4. These counts were compared with those obtained in normal adult cats.The normal adult distribution of the callosal neurons results from the gradual postnatal reduction of a more widespread juvenile population. Binocular visual deprivation by lid suturing dramatically decreases the final number of callosal neurons and narrows their region of distribution (callosal zone) in areas 17 and 18. A less severe reduction in the final number of callosal neurons is caused by bilateral enucleation, which also increases the width of the callosal zone compared to that of normal cats. Thus, visual experience is necessary for the normal stabilization of juvenile callosal connections. However, since some callosal neurons form connections in the absence of vision, other influences capable of stabilizing juvenile callosal neurons also exist. These influences are probably antagonized by destabilizing influences or inhibited, when the eyes are intact.This work was supported by Swiss National Science Foundation grant 2.219.0.78 to Dr. G.M. Innocenti; Dr. D.O. Frost received a fellowship from the American-Swiss Foundation for Scientific Exchange     

Ontogenesis of receptive field characteristics in the dorsal lateral geniculate nucleus of the rabbit

Summary The responses of rabbit dorsal lateral geniculate neurons to light or optic nerve shock were tested for 415 units in 43 rabbit pups 2–20 days of age. Units were driven by optic nerve shock at the youngest ages tested, but could not be driven by light until postnatal day six. Examples of each of the three prominent categories of receptive fields found in the adult were first observed at 8 days of age. Cells with receptive field properties not characteristic of the dorsal lateral geniculate nucleus of the adult were encountered until 17 days of age. The percentage of neurons with uniform and motion sensitive receptive fields approached adult levels soon after eye opening (11–12 days) but the percentage of cells with concentric receptive fields showed a steady increase throughout the neonatal period studied. The relevance of our data to the development of the visual response in the dorsal lateral geniculate nucleus and striate cortex is discussed.     

Ontogenetic Characteristics of the Organization of Corticocortical Connections between the Primary Visual Cortex and the Lateral Suprasylvian Area of the Cat Brain

Studies on 10 cats aged five and 12 weeks included qualitative and quantitative analyses of the distribution in field 17 of initial neurons organizing corticocortical connections with the posteromedial lateral suprasylvian gyrus (PMLS) of the brain using retrograde labeling with horseradish peroxidase. The PMLS area is a higher center for processing information relating to the movement of visual stimuli. Ontogenetic characteristics of the formation of the ordered (clustered) organization of initial neurons in field 17 were identified. An age-related decrease in the density of initial neurons in field 17 was found, from 125.2 ± 69.8 cells/mm² in kittens aged five weeks to 34.7 ± 17.4 cells/mm² in 12-week-old kittens (p = 0.05). During the period between postnatal weeks 5 and 12, there was an increase in the size of the labeled area containing the majority of initial neurons. The morphofunctional aspects of the formation of the ordered structure of corticocortical connections between field 17 and the PMLS during postnatal ontogenesis and its possible relationship with the development of the function of the visual perception of moving objects are discussed.     

Features of the establishment of the spontaneous activity of neurons of the trigeminal sensory nuclei of viable sections of the rat brainstem in postnatal ontogenesis

An attempt was made to characterize the features of the development of the neurons of the sensory trigeminal nuclei, a basic structure of the sensory support of alimentary behavior, in the late stages of postnatal ontogenesis. A technique involving viable sections of the brainstem of infant rats at the ages of two, four, and eight weeks was utilized. An increase with age in the number of neurons possessing spontaneous activity (44% at two weeks; 69% at eight weeks), an increase in the frequency of discharges, the appearance by the fourth week of a population of cells with high-frequency spontaneous activity, and an increase in the number of such neurons by the eighth week. Three types of background-active neurons were distinguished: episodic, continuous, and group; and the dynamics of the change in the ratios of these types with age was demonstrated. Significant changes with age were not found in resting potentials, although a tendency to its increase takes place between the second and eighth weeks of postnatal development.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 41, No. 1, pp. 139–146, January–February, 1991.     

A developmental study of retinal afferents and visual responses in the cat pretectum

Summary Neuronal responses in the pretectum (PT) were analyzed in 4–16 week old kittens after visual and electrical stimulation and compared with adult responses from a previous study. All three retinal fiber types projecting to the adult PT could be electrically activated in kittens from 4 weeks on. There was a dramatic reduction of response latencies to electric shocks to retinal afferents applied at the optic chiasm (OX) and optic tract (OT) in postsynaptic cells as a function of age, involving X-, Y-, and Wfibers. At four through six weeks postnatally the reduction in latency was found to be due to enhanced signal transmission at the axonal terminal region. Latency reduction continued after six weeks of life due to sharp increases in conduction velocity of the afferent fibers. Different steps in the maturation of visual response specifity were found for neurons of different functional types. Possible relationships are discussed between the development of neuronal responses of pretectal cells and the maturation of oculomotor behavior.     

The morphology of baroreceptors of the aortic arch of puppies during postnatal development

Summary Examination of the thick nerve fibers and of the receptors of the reflexogenous zones of the aortic arch of healthy puppies of various ages showed that in the postnatal period the baroreceptors of the aortic arch gradually acquired the characteristic features of normal adult animals. The first sign of these characteristic features appeared by the 25–30th day, but after two months and later the baroreceptors and the corresponding afferent fibers displayed all the features present in the corresponding structures of healthy adult animals.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 56, No. 12, pp. 92–96, December, 1963     

Functional and developmental analysis of a visual corticopretectal pathway in the cat: a neuroanatomical and electrophysiological study

Summary The sensory corticopretectal projection in the cat and in its postnatal development were investigated combining neuroanatomical and electrophysiological techniques. The anatomical pattern of fiber termination was studied in relation to age using the anterograde HRP tracing method. Large injections were made in areas 17 and 18 of one or both hemispheres in 1–13 week old kittens and cats. Terminal label in the ipsilateral pretectum was seen only after the fourth week of life. Electrical stimulation in the same cortical areas evoked postsynaptic orthodromic excitation in 9–18% of cells at 4 weeks increasing to about 60% in the adult. In cats, but not in kittens, successful stimulation depended on the retinotopic matching of stimulation and recording sites. In adult cats a high incidence of direction and velocity tuning and a high degree of binocularity were seen in cells driven by the cortex as opposed to cells not so driven. Cortex driven cells in cats and kittens received convergent retinal input mainly via direct W-fibers, whereas cells not driven from cortex shock mainly received delayed W-fiber input. In kittens visual responses lacked sensitivity for direction and high movement velocity of patterns until 6 weeks postnatally, whereas ocular dominance distribution was not age-dependent.