Postnatal development of neuropeptide Y-containing neurons in the visual cortex of normal- and dark-reared rats.

The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons in the visual cortical areas (17, 18 and 18a) has been studied in Wistar rats reared under normal lighting conditions or in complete darkness. Immunohistochemistry on paraffin sections at postnatal days (P)7, 14, 21, 30 and 60 showed an overall similarity in laminar distribution of NPY neurons in all 3 visual areas of both normal- and dark-reared animals. The pattern of development of NPY neurons was characterized by an increase in their density from P7 to reach a peak at P21 followed by a decline to 37-47% of peak levels at P60. However, this diminution was not so great in dark-reared rats as in the normal, since the density only decreased to 62-78% of peak levels. At P60 the resulting differences in neuron density were marked in areas 17 and 18, where the dark-reared had 75% more cells than normal, and moderate in area 18a (30% more than normal). These results suggest that the normal decline in NPY neurons is not entirely mediated by visual experience since it takes place, albeit to a modified extent, in its total absence.     

Comparison of neuronal and glial numerical density in primary and secondary visual cortex of man

Summary The numerical density of neurons and glial cells was estimated in visual area 18 of the adult human cerebral cortex and compared with that of area 17. Blocks of areas 17 and 18 came from the same brains and this allowed the comparison of 1) neuronal and glial numerical densities through the whole cortical depth with calculation of the neuron/glia ratio, 2) neuronal and glial numbers under one square millimeter of cortical surface, and 3) neuronal numerical densities in three groups of identified layers. The mean neuronal density is approximately 40000 neurons/mm³ in area 17 and 31500/m³ in area 18. The mean glial density is around 27000/mm³ in area 17 and 32000/mm³ in area 18. This gives a neuron/glia ratio of approximately 1.5 in area 17 and of 1.0 in area 18, but the total cellular density is similar in both areas. There are about 90000 neurons and 64000 glial cells under one square millimeter of cortical surface in area 17, and some 73000 neurons and 74000 glial cells in area 18. The higher neuronal density in area 17 is found through the whole depth of cortex and does not seem to be more pronounced in layer IVc of area 17 compared to layer IV in area 18 than in the groups of layers II–III and V–VI.     

Longterm impairment of cat optokinetic nystagmus following visual cortical lesions

Summary Binocular and monocular gain of optokinetic nystagmus (OKN), OKN dynamics, vestibulo-ocular reflex (VOR) and VOR adaptation were measured in 5 normal cats and in 5 cats which underwent bilateral visual cortical lesions involving the 17–18 complex at least 4 months before testing. We observed longterm deficits after bilateral lesions involving area 17 and variable parts of area 18 but failed to observe deficits after 18–19 lesions. These deficits were limited to the OKN gain and the build-up time constant of OKN; the VOR and the optokinetic after-nystagmus (OKAN) time constant were within normal limits. Our results suggest that areas 17–18 operate in parallel to control the encoding of retinal slip velocity at the level of the nucleus of the optic tract (NOT) and the accessory optic system (AOS), which are known to represent the initial stage of the optokinetic pathways.     

Characteristics of Cytochrome Oxidase Activity in Visual System Neurons in Kittens Reared in Conditions of Flashing Illumination

The studies reported here addressed the effects of flashing (15 Hz) lights on the metabolic activity of visual system neurons in animals reared in condition of crepuscular illumination. Activity of the respiratory enzyme cytochrome oxidase was detected in the cortex of visual areas 17 and 18 and in the lateral geniculate body in kittens. The results showed that kittens subjected to this stimulation, unlike intact kittens and kittens reared in conditions of crepuscular illumination, showed a change in the pattern of cytochrome oxidase distribution in cortical field 17 consisting of the appearance of alternating areas of increased and decreased enzyme activity in layers III and IV. In cortical field 18 and the lateral geniculate body, experimental kittens showed no changes in the cytochrome oxidase activity distribution pattern. It is suggested that flashing illumination leads to disturbance of the balance in activity in the Y and X conducting channels of the visual system.__________Translated from Morfologiya, Vol. 126, No. 5, pp. 20–23, September–October, 2004.Doctor of Sciences F. M. Makarov     

Neonatal superior collicular lesions alter visual callosal development in hamster

Summary Visual callosal connections were examined using autoradiographic (ARG) and horse-radish peroxidase (HRP) techniques in normal adult hamsters, and in adults subjected to ablation of the superficial tectal laminae at birth. Additional ARG and HRP experiments were carried out in hamsters 1–27 days of age in order to describe the normal development of this pathway. Neonatal collicular lesions, which deprived visual cortical neurons of a major terminal zone in the midbrain, substantially altered the visual callosal pathway. In the lesioned animals, the numbers of supragranular callosal cells in the 17–18a border region and lamina VI callosal neurons in medial area 17 were significantly greater than normal. The ARG experiments demonstrated additional clearcut abnormalities in the visual callosal pathway of the lesioned hamsters. First, the mediolateral extent of the supragranular callosal zone around the 17–18a border was increased. Secondly, dense label was visible over lower layer V and lamina VI throughout area 17. Finally, labelling in lamina I could also be observed across the entire mediolateral extent of area 17.Experiments in the developing hamsters suggested that some of the abnormalities observed in the lesioned animals may have resulted from the maintenance of normally transient developmental states. During the first postnatal week, both callosal cells and anterograde labelling were evenly distributed throughout the dorsal posterior neocortex, but only in the subplate region. During the second postnatal week, supragranular callosal cells were also labelled in both medial and lateral area 17, but from their first appearance, they were always most numerous in the 17–18a border region. At the same time callosal axons invaded the supragranular laminae, but only near the 17–18a border. By the end of the second postnatal week, the visual callosal pathway was very similar to that in the adult.     

Fetal neocortical transplants grafted to the cerebral cortex of newborn rats receive afferents from the basal forebrain,locus coeruleus and midline raphe

Summary Fetal cerebral neocortex (E15–17) was grafted into the cerebral hemisphere of newborn (0–1 day old) rats. Grafts were placed into cortical aspiration lesion cavities made immediately prior to grafting. At maturity, transplant afferents were examined by injecting the retrogradely transported fluorescent dyes diamidino yellow and fast blue into the grafts. Retrogradely-labeled neurons were histologically observed within several regions of the host brain including the basal forebrain, locus coeruleus and dorsal raphe areas. The topographical distribution within these areas resembled the normal labeling patterns described in previous reports.     

Somatostatin and cognitive dysfunction in Alzheimer's disease

Multiple research groups have documented reductions in cortical somatostatin‐like immunoreactivity (SRIF) in Alzheimer's disease (AD). This study investigated the relationship between cerebral cortical SRIF levels and concurrent measures of specific neuropsychological functions in early‐to‐middle‐stage AD patients. Biopsy samples obtained from nondominant frontal cortex of 5 patients with histopathologically confirmed AD were assayed for SRIF. Concurrent measures of intelligence, memory, language, visuoperception, visuoconstruction, attention, concentration, reaction time, and overall dementia severity were obtained. Close associations were observed between SRIF and dementia severity, four‐choice visual reaction time, and visuoperceptual and visuoconstructional abilities. No relationship was observed between SRIF and the remaining neuropsychological measures. Results are consistent with the hypothesis that the functional deficits in AD are caused, in large part, by a loss of cortico‐cortical projection neurons and a subsequent dissociation of specific cortical functional areas from one another.     

Influences of cortico-tectal and intertectal connections on visual responses in the cat's superior colliculus

Summary Our experiments, utilizing electrical shocks applied to the lateral- or supra-sylvian gyrus of the cortex, demonstrate an initially excitatory (latency 2–10 msec) but predominantly inhibitory influence of cortico-tectal afferents on the discharge of tectal neurons. Primary or secondary inhibition in tectal cells after cortical stimulation suppressed spontaneous or visually driven activity and limited the frequency of stimulation which tectal neurons could follow.The main influence of the contralateral colliculus on visual responses of tectal cells is inhibitory but again some principally monosynaptic intertectal connections evoked initial excitation (latency 3–10 msec) after electrical stimulation of the contralateral optic tract.Removal of the visual areas 17, 18 and 19 did not cause a loss of movement- or direction-selectivity in neurons of the superior colliculus. Cooling of the occipital cortex, while recording from direction-selective tectal neurons did not alter their essential response characteristics. The response to cortical shocks disappeared in tectal neurons during cooling but could be restored by rewarming of the cortex.It could not be confirmed in our experiments that excitation and movement- or direction-selectivity of neurons in the superior colliculus depend on a specific input from areas 17, 18 and 19 of the cortex.     

Morphology of visual callosal neurons with different locations,contralateral targets or patterns of development

In kittens, callosally projecting neurons were labeled by retrograde transport of FITC- (fluorescein isothiocyanate)- and TRITC- (tetramethylrhodamine isothiocyanate)-conjugated latex microspheres injected in two different visual areas (17, 17/18, 19, or postero-medial lateral suprasylvian; PMLS) at postnatal day 3. At postnatal day 57 more than 1200 labeled neurons in visual cortical areas were intracellularly injected with 3% lucifer yellow (LY) in perfusion-fixed slices of the contralateral hemisphere. The distribution of labeled neurons was charted, and LY-filled neurons were classified on the basis of their area and layer of location, and dendritic pattern. The dendritic arbors of 120 neurons were computer reconstructed. For the basal dendrites of supragranular pyramidal neurons a statistical analysis of number of nodes, internodal and terminal segment lengths, and total dendritic length was run relative to the area of location and axonal projection. Connections were stronger between homotopic than between heterotopic areas. Overall tangential and laminar distributions depended on the area injected. Qualitative morphological differences were found among callosally projecting neurons, related to the area of location, not to that of projection. In all projections from areas 17 and 18, pyramidal and spinous stellate neurons were found in supragranular layers. In contrast, spinous stellate neurons lacked in projections from area 19, 21a, PMLS and postero-lateral lateral suprasylvian (PLLS). In all areas, the infragranular neurons showed heterogeneous typology, but in PMLS no fusiform cells were found. Quantitative analysis of basal dendrites did not reveal significant differences in total dendritic length, terminal, or intermediate segment length among neurons in area 17 or 18, and this was related to whether they projected to contralateral areas 17–18 or PMLS. All injections produced exuberant labeling in area 17. No differences could be found between neurons in area 17 (with transient axons through the corpus callosum) and neurons near the 17/18 border (which maintain projections to the corpus callosum). In conclusion, morphology of callosally projecting neurons seems to relate more to intrinsic specificities in the cellular composition of each area than to the area of contralateral axonal projection or the fate of callosal axons.     

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

Summary 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 occured in response to 12.5–100 M 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 NMDAevoked Ca uptake at agonist concentrations greater than 25 M. These data suggest that even brief manipulations of sensory experience are sufficient to alter visual cortical calcium regulation.     

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     

The experimental pathology of higher nervous activity cholinosensitivity as an indicator of functional differences of neurons of the cortex of young and old rabbits

The cholinosensitivity of neurons of the motor cortex of young and old rabbits was studied. It was shown that muscarinic activation in the cells of old animals is encountered half as often than in young animals. The age-related decrease in cholinosensitivity is explained by an insufficiency of the overall activation of neurons in old animals. The change in the functional state of the cells of the motor cortex leads to the fact that the frequency of impulse activity of neurons associated with movement proves to be insufficient for the achievement of effective cortical control of motor functions.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 41, No. 6, pp. 1222–1230, November–December, 1991.     

Response properties of visual cortical neurons in cats reared in stroboscopic illumination

1. The response properties of 182 units were studied in the primary visual cortices (155 in area 18 and 27 in area 17) in eight cats reared from birth in a stroboscopically illuminated environment (frequency, 2/s; duration, 200 microseconds). Multihistogram quantitative testing was carried out in 82 units (64 in area 18 and 18 in area 17). Two hundred three neurons recorded and quantitatively tested in areas 17 and 18 of the normal adult cat were used for comparison. 2. Spatial characteristics of receptive fields investigated using hand-held stimuli were found to be abnormal. The correlation between receptive-field width and eccentricity was lost in area 18 and consequently, receptive fields were significantly wider in area 18 subserving central vision. Cells could be classified according to the spatial characteristics of their receptive fields. There was a much smaller proportion of end-stopped cells in strobe-reared animals. Orientation tuning in the deprived animals was normal except for a small number of cells that showed no selectivity for stimulus orientation. 3. Compilation of velocity-response curves made it possible to classify areas 17 and 18 neurons into four categories: velocity low-pass, velocity broad-band, velocity tuned, and velocity high-pass cells. The proportion of velocity high-pass cells was reduced in area 18 subserving peripheral vision, as was the proportion of velocity-tuned cells in area 18 subserving central vision. 4. In the strobe-reared animal velocity sensitivity was somewhat different from that of the normal animal. Neurons in area 18 subserving the peripheral visual field failed to respond to fast velocities. Neurons in area 17 subserving the central visual field in strobe-reared animals responded to slightly higher velocities than in the normal animal. 5. In the deprived animals the number of neurons that were selective to the direction of motion was strongly reduced. The majority of neurons failed to show a selectivity for direction at all velocities. A number of neurons could be directional at some velocities but were unreliable, since they inverted their preferred direction with velocity changes. 6. Binocular convergence onto visual cortical cells was perturbed. In area 18 the majority of neurons were driven by the contralateral eye. In area 17 most neurons could be driven only by either the ipsilateral or contralateral eye. 7. Quantitative testing (of direction selectivity, sensitivity to high velocities, response latency, and strength) and qualitative testing (receptive-field width, end stopping, and ocular dominance) showed that the normal influence of eccentricity on functional properties was strongly reduced by strobe rearing.     

Age dependence of the effect of squint on cells in Kittens' visual cortex

Summary The period of susceptibility of the visual cortex of kittens to the effect of squint is limited to the first three postnatal months. The reduction of binocularity found in these kittens as reflected by the distribution of neurons according to their ocular dominance is especially emphasized in animals operated on between the ages of 4–7 weeks in comparison to animals operated on between the ages of 8–11 weeks. The proportion of monocularly dominated neurons within the first three postnatal months is significantly (0.05 > p > 0.025) reduced with age. Similar effect on cortical neurons was found for animals who were under the influence of squint for 6 weeks or 15 months and for animals with wide range of deviation angles.     

Effect of microiontophoretic application of acetylcholine on visual cortical evoked activity to direct cortical stimulation

Responses of visual cortical neurons (area 17) to direct cortical sitmulation of visual areas 18 and 19 were investigated in acute experiments on adult unanesthetized cats, immobilized with diplacin, under local anesthesia, after microiontophoretic application of acetylcholine. Selectivity of the action of acetylcholine on the individual components of the unit responses to direct cortical stimulation was established. The role of acetylcholine as mediator of information in the mechanisms of transcortical interneuronal interaction within the visual system is discussed.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 62, No. 3, pp. 342–348, March, 1976.     

Effects of alternating monocular occlusion on the development of visual callosal connections

Summary During normal postnatal development there is a partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. Visual experience early in life can modulate this process. In the present study, we investigated how restricting visual experience to alternating monocular occlusion affects the development of the callosal connections of cortical areas 17 and 18. Alternating monocular occlusion exaggerates the normally occurring partial elimination of immature callosal projections: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum and marginally increases the distribution of these neurons across areas 17 and 18. Examination of these data in the context of the effects of other types of abnormal early visual experience on the corpus callosum and on the anatomy and physiology of areas 17 and 18 indicates that the postnatal development of the corpus callosum is under the control of multiple, interacting influences which differ in the magnitude and quality of their effects. The data also support the conclusion, drawn from our results in prior studies, that normal visual stimulation is necessary for the stabilization of the normal complement of callosal projections.     

Lesion of areas 17/18/19: effects on the cat's performance in a binary detection task

Summary The ability of two cats to discriminate between two geometrical outline patterns in the presence of superimposed Gaussian visual noise — i.e. in a binary detection task — was tested before and after bilateral removal of cortical areas 17, 18 and 19. The detection probability P_D was measured as a function of the signal-to-noise ratio. After a lesion of areas 17, 18 and 19 both cats were unable to carry out the discrimination tasks. Their detection performance dropped to chance level, but after an extensive phase of retraining (3 months) they regained the ability to discriminate visual patterns. It was thus possible to obtain detection curves and to determine a measure of a performance which is predominantly bound to be mediated by extra-geniculo-cortical systems. The detection capacity was abnormally low with both large and small patterns. However, the detection of stationary small patterns was similar to the performance of cats with 17/18 lesions; the detection of stationary large patterns was only slightly better than the detection of small patterns and much worse than the comparable performance of cats with 17/18 lesions. Furthermore the cats with lesions of areas 17/18/19 were unable to discriminate moving patterns, their performances being at chance level, whereas for the cats with 17/18 lesions the detection of moving and stationary patterns was equal.Supported by the Deutsche Forschungsgesellschaft     

Spatial frequency properties in area 18 during inactivation of area 17 in cats

 The aim of this investigation was to understand the functions of long horizontal connections projecting from area 17 to area 18 in cats. The animals were anesthetized and prepared for recording single-cell responses to sine-wave gratings in area 18. Neuronal activity was analyzed under three conditions: prior to, during, and after inactivation of a circumscribed region of area 17. The latter was depressed with micro-injections of GABA. Cells in both areas were in close retinotopic correspondence. Cells were classified as simple and complex types. Globally, simple cells were less affected than complex units, and those which were affected shifted their optimal spatial frequency to higher values. Complex neurons were more often influenced by the interruption of area 17 input. Namely, the peaks of the tuning curves were displaced on the x-axis to a new optimal spatial frequency. This effect was obtained by a dual change: a decline in the discharge strength to the optimal spatial frequency and an enhancement to nonoptimal spatial frequency. Contrast sensitivity function disclosed similar shifts of optimal spatial frequencies. Likewise bandwith, spatial resolution, high cutoff, and low cutoff were modified to a greater extent in complex cells. It appears that there is no relationship between areas 17/18 orientation difference and the modifications observed in tuning curves to spatial frequencies. The results suggest that neurons of area 18 may carry multiple-frequency channels and that area 17 facilitates the emergence of one particular spatial frequency. Received: 26 February 1996 / Accepted: 27 August 1996     

A comparison of visual callosal organization in normal,bilaterally enucleated and congenitally anophthalmic mice

Summary Visual callosal connections were examined using the horseradish peroxidase (HRP) technique in normal, neonatal and adult C57BL mice, and in adults of this strain which were bilaterally enucleated within 12 h of birth. In addition, callosal connections were also delineated in two strains of congenitally anophthalmic mice, ZRDCTan and or^J. Material from 129/J mice served as controls for the latter strain. In normal adults anterograde labelling and HRP labelled cells were visible primarily at the borders of area 17. In the 17–18a border region, labelled neurons were located primarily in layers II–III and V. In the medial striate cortex, a small number of labelled cells were present, primarily in lamina VI. Anterograde HRP labelling in the normal adults was also located primarily at the borders of area 17. At the 17–18a border, it was very heavy in layers V and VI, somewhat lighter in layer IV, and fairly dense in layers II–III and the lower half of lamina I. Labelling indicative of anterograde HRP transport was also visible in lowermost lamina V and layer VI across the entire mediolateral extent of area 17. In normals injected with HRP on postnatal day 2 and perfused 24 h later, callosal neurons were distributed throughout the dorsal posterior neocortex, primarily in layers V and VI. Only a very few labelled cells were visible in the supragranular laminae. In adult mice blinded at birth, the zone of callosal cells and terminals extended much further into area 17 than in normals, but aside from the anterograde labelling in layer VI and lowermost lamina V, the medial one-third of the striate cortex was still for the most part devoid of callosal cells and fibers. The laminar distributions of the labelled cells and anterograde transport in the blinded animals were the same as in the normal mice. In both strains of anophthalmic mice the pattern of callosal connections was unlike that in either the normals or neonatal enucleates. In the caudal visual cortex, callosal cells and anterograde transport indicative of terminal labelling were visible primarily in the 17–18a border area. Rostrally, however, they were both distributed in multiple (two-three) patches within area 17. Serial reconstructions demonstrated that these patches tended to be aligned in stripes which ran parallel to the 17–18a border. One of these was always located at the 17–18a border, and here the laminar distribution of labelled cells and anterograde labelling was the same as in the normals. In the more medial patches, however, labelled cells and anterograde labelling were confined almost completely to layers II and III. The distribution of callosal cells in neonatal ZRDCT-an mice was not appreciably different from that in C57BL mice of the same age.     

Callosal projections between areas 17 in the adult tree shrew (Tupaia belangeri)

Summary In the primary visual cortex (area 17) of the tree shrew (Tupaia belangeri) neurons projecting to the contralateral area 17 via the corpus callosum were identified by horseradish peroxidase histochemistry (HRP, WGA-HRP). The distribution of homotopic and heterotopic connections was studied. We found that a narrow stripe of area 17 close to the dorsal area 17/18 border — which corresponds to the visual field along the vertical meridian — is connected via homotopic callosal projections. The adjacent dorsal part of area 17, which largely corresponds to the binocular visual field, is connected via homotopic as well as heterotopic projections. Heterotopic projections originate in the cortical stripe along the area 17/18 border and their contralateral targets are displaced medially. Callosal neurons are located mostly in supragranular but also occur in infragranular layers. The supragranular neurons in general are pyramidal cells. In addition to these findings, we confirmed earlier reports on ipsilateral projections of the primary visual area to the dLGN, the claustrum, area 18 and other visual areas.The authors wish to dedicate this paper to Prof. W. Lierse in honour of his 60th birthday